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Erschienen in: Virchows Archiv 3/2014

01.03.2014 | Invited Review

Biomarkers for gastric cancer: prognostic, predictive or targets of therapy?

verfasst von: Cecília Durães, Gabriela M. Almeida, Raquel Seruca, Carla Oliveira, Fátima Carneiro

Erschienen in: Virchows Archiv | Ausgabe 3/2014

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Abstract

Gastric cancer is an aggressive disease often diagnosed at an advanced stage. Despite improvements in surgical and adjuvant treatment approaches, gastric cancer remains a global public health problem with a 5-year overall survival of less than 25 %. This is a heterogeneous disease, both in terms of biology and genetics, and many prognostic biomarkers have been pointed out in the literature; nevertheless, their application remains debatable. In this review, we opted to give relevance to those biomarkers that have been the subject of studies with significant statistical power, which have been replicated and have been/are in targeted therapy clinical trials and, which as a consequence, have their prognostic and/or predictive value established. Some gastric cancer biomarkers that may help in defining the course of treatment are also discussed. Accepted practical guidelines, wet-lab protocols for the detection of these biomarkers, as well as ongoing and completed clinical trials have been compiled. In summary, clinical approaches based on the combination of correct staging with targeted and conventional systemic therapies may improve gastric cancer patients’ outcome, but are only in their infancy. Some major challenges in identifying reliable prognostic/predictive biomarkers are individual genetic variation and tumour heterogeneity that often influence response to therapy and drug resistance. Prognostic and predictive biomarkers may nevertheless be extremely valuable to correctly stratify gastric cancer patients for treatment and, ultimately, improve survival.
Literatur
3.
Zurück zum Zitat Houghton J, Wang TC (2005) Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 128(6):1567–1578CrossRefPubMed Houghton J, Wang TC (2005) Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 128(6):1567–1578CrossRefPubMed
4.
Zurück zum Zitat Yamashita K, Sakuramoto S, Katada N, Futawatari N, Moriya H, Hirai K, Kikuchi S, Watanabe M (2009) Diffuse type advanced gastric cancer showing dismal prognosis is characterized by deeper invasion and emerging peritoneal cancer cell: the latest comparative study to intestinal advanced gastric cancer. Hepatogastroenterology 56(89):276–281PubMed Yamashita K, Sakuramoto S, Katada N, Futawatari N, Moriya H, Hirai K, Kikuchi S, Watanabe M (2009) Diffuse type advanced gastric cancer showing dismal prognosis is characterized by deeper invasion and emerging peritoneal cancer cell: the latest comparative study to intestinal advanced gastric cancer. Hepatogastroenterology 56(89):276–281PubMed
6.
Zurück zum Zitat Oliveira C, Senz J, Kaurah P, Pinheiro H, Sanges R, Haegert A, Corso G, Schouten J, Fitzgerald R, Vogelsang H, Keller G, Dwerryhouse S, Grimmer D, Chin SF, Yang HK, Jackson CE, Seruca R, Roviello F, Stupka E, Caldas C, Huntsman D (2009) Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 18(9):1545–1555. doi:10.1093/hmg/ddp046 PubMedCentralCrossRefPubMed Oliveira C, Senz J, Kaurah P, Pinheiro H, Sanges R, Haegert A, Corso G, Schouten J, Fitzgerald R, Vogelsang H, Keller G, Dwerryhouse S, Grimmer D, Chin SF, Yang HK, Jackson CE, Seruca R, Roviello F, Stupka E, Caldas C, Huntsman D (2009) Germline CDH1 deletions in hereditary diffuse gastric cancer families. Hum Mol Genet 18(9):1545–1555. doi:10.​1093/​hmg/​ddp046 PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat Kitagawa Y, Takeuchi H, Takagi Y, Natsugoe S, Terashima M, Murakami N, Fujimura T, Tsujimoto H, Hayashi H, Yoshimizu N, Takagane A, Mohri Y, Nabeshima K, Uenosono Y, Kinami S, Sakamoto J, Morita S, Aikou T, Miwa K, Kitajima M (2013) Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan. J Clin Oncol. doi:10.1200/JCO.2013.50.3789 PubMed Kitagawa Y, Takeuchi H, Takagi Y, Natsugoe S, Terashima M, Murakami N, Fujimura T, Tsujimoto H, Hayashi H, Yoshimizu N, Takagane A, Mohri Y, Nabeshima K, Uenosono Y, Kinami S, Sakamoto J, Morita S, Aikou T, Miwa K, Kitajima M (2013) Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan. J Clin Oncol. doi:10.​1200/​JCO.​2013.​50.​3789 PubMed
11.
Zurück zum Zitat GASTRIC Group, Oba K, Paoletti X, Bang YJ, Bleiberg H, Burzykowski T, Fuse N, Michiels S, Morita S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, Shitara K, Tsuburaya A, Van Cutsem E, Buyse M (2013) Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis. Eur J Cancer 49(7):1565–1577. doi:10.1016/j.ejca.2012.12.016 CrossRefPubMed GASTRIC Group, Oba K, Paoletti X, Bang YJ, Bleiberg H, Burzykowski T, Fuse N, Michiels S, Morita S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, Shitara K, Tsuburaya A, Van Cutsem E, Buyse M (2013) Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis. Eur J Cancer 49(7):1565–1577. doi:10.​1016/​j.​ejca.​2012.​12.​016 CrossRefPubMed
13.
Zurück zum Zitat Pietrantonio F, Braud F, Da Prat V, Perrone F, Pierotti MA, Gariboldi M, Fanetti G, Biondani P, Pellegrinelli A, Bossi I, Di Bartolomeo M (2013) A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res 33(4):1257–1266PubMed Pietrantonio F, Braud F, Da Prat V, Perrone F, Pierotti MA, Gariboldi M, Fanetti G, Biondani P, Pellegrinelli A, Bossi I, Di Bartolomeo M (2013) A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res 33(4):1257–1266PubMed
14.
Zurück zum Zitat Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2010) AJCC cancer staging manual, 7th edn. New York, Springer Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2010) AJCC cancer staging manual, 7th edn. New York, Springer
15.
Zurück zum Zitat Japanese Research Society for Gastric Cancer (1993) The general rules for the gastric cancer study in surgery and pathology, 12 edn. Japanese Research Society for Gastric Cancer, Kanahara Shuppan, Tokyo Japanese Research Society for Gastric Cancer (1993) The general rules for the gastric cancer study in surgery and pathology, 12 edn. Japanese Research Society for Gastric Cancer, Kanahara Shuppan, Tokyo
16.
Zurück zum Zitat Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ (2004) Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer—pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol 22(12):2395–2403. doi:10.1200/JCO.2004.08.154 CrossRefPubMed Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ (2004) Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer—pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol 22(12):2395–2403. doi:10.​1200/​JCO.​2004.​08.​154 CrossRefPubMed
17.
18.
Zurück zum Zitat Sehdev A, Catenacci DV (2013) Gastroesophageal cancer: focus on epidemiology, classification, and staging. Discov Med 16(87):103–111PubMed Sehdev A, Catenacci DV (2013) Gastroesophageal cancer: focus on epidemiology, classification, and staging. Discov Med 16(87):103–111PubMed
19.
Zurück zum Zitat Lee J, Ou SH (2013) Towards the goal of personalized medicine in gastric cancer—time to move beyond HER2 inhibition. Part I: targeting receptor tyrosine kinase gene amplification. Discov Med 15(85):333–341PubMed Lee J, Ou SH (2013) Towards the goal of personalized medicine in gastric cancer—time to move beyond HER2 inhibition. Part I: targeting receptor tyrosine kinase gene amplification. Discov Med 15(85):333–341PubMed
23.
Zurück zum Zitat Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K, Isola J (2005) Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16(2):273–278. doi:10.1093/annonc/mdi064 CrossRefPubMed Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K, Isola J (2005) Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16(2):273–278. doi:10.​1093/​annonc/​mdi064 CrossRefPubMed
24.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK, To GATI (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697. doi:10.1016/S0140-6736(10)61121-X CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK, To GATI (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697. doi:10.​1016/​S0140-6736(10)61121-X CrossRefPubMed
25.
Zurück zum Zitat Bar-Sela G, Hershkovitz D, Haim N, Kaidar-Person O, Shulman K, Ben-Izhak O (2013) The incidence and prognostic value of HER2 overexpression and cyclin D1 expression in patients with gastric or gastroesophageal junction adenocarcinoma in Israel. Oncol Lett 5(2):559–563. doi:10.3892/ol.2012.1031 PubMedCentralPubMed Bar-Sela G, Hershkovitz D, Haim N, Kaidar-Person O, Shulman K, Ben-Izhak O (2013) The incidence and prognostic value of HER2 overexpression and cyclin D1 expression in patients with gastric or gastroesophageal junction adenocarcinoma in Israel. Oncol Lett 5(2):559–563. doi:10.​3892/​ol.​2012.​1031 PubMedCentralPubMed
26.
Zurück zum Zitat Barros-Silva JD, Leitao D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, Bento MJ, Santos L, Ferreira P, Rego S, Brandao C, Carneiro F, Lopes C, Schmitt F, Teixeira MR (2009) Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer 100(3):487–493. doi:10.1038/sj.bjc.6604885 PubMedCentralCrossRefPubMed Barros-Silva JD, Leitao D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, Bento MJ, Santos L, Ferreira P, Rego S, Brandao C, Carneiro F, Lopes C, Schmitt F, Teixeira MR (2009) Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer 100(3):487–493. doi:10.​1038/​sj.​bjc.​6604885 PubMedCentralCrossRefPubMed
27.
Zurück zum Zitat Aizawa M, Nagatsuma AK, Kitada K, Kuwata T, Fujii S, Kinoshita T, Ochiai A (2013) Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population. Gastric Cancer. doi:10.1007/s10120-013-0239-9 PubMed Aizawa M, Nagatsuma AK, Kitada K, Kuwata T, Fujii S, Kinoshita T, Ochiai A (2013) Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population. Gastric Cancer. doi:10.​1007/​s10120-013-0239-9 PubMed
28.
Zurück zum Zitat Gordon MA, Gundacker HM, Benedetti J, Macdonald JS, Baranda JC, Levin WJ, Blanke CD, Elatre W, Weng P, Zhou JY, Lenz HJ, Press MF (2013) Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol 24(7):1754–1761. doi:10.1093/annonc/mdt106 CrossRefPubMed Gordon MA, Gundacker HM, Benedetti J, Macdonald JS, Baranda JC, Levin WJ, Blanke CD, Elatre W, Weng P, Zhou JY, Lenz HJ, Press MF (2013) Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol 24(7):1754–1761. doi:10.​1093/​annonc/​mdt106 CrossRefPubMed
29.
Zurück zum Zitat Grabsch H, Sivakumar S, Gray S, Gabbert HE, Muller W (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol 32(1–2):57–65. doi:10.3233/CLO-2009-0497 PubMed Grabsch H, Sivakumar S, Gray S, Gabbert HE, Muller W (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol 32(1–2):57–65. doi:10.​3233/​CLO-2009-0497 PubMed
30.
Zurück zum Zitat Okines AF, Thompson LC, Cunningham D, Wotherspoon A, Reis-Filho JS, Langley RE, Waddell TS, Noor D, Eltahir Z, Wong R, Stenning S (2013) Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol 24(5):1253–1261. doi:10.1093/annonc/mds622 CrossRefPubMed Okines AF, Thompson LC, Cunningham D, Wotherspoon A, Reis-Filho JS, Langley RE, Waddell TS, Noor D, Eltahir Z, Wong R, Stenning S (2013) Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol 24(5):1253–1261. doi:10.​1093/​annonc/​mds622 CrossRefPubMed
32.
Zurück zum Zitat Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sanchez Rovira P, Piccart-Gebhart MJ, team Hs (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36. doi:10.1016/S0140-6736(07)60028-2 CrossRefPubMed Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sanchez Rovira P, Piccart-Gebhart MJ, team Hs (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36. doi:10.​1016/​S0140-6736(07)60028-2 CrossRefPubMed
33.
Zurück zum Zitat Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792. doi:10.1056/NEJM200103153441101 CrossRefPubMed Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792. doi:10.​1056/​NEJM200103153441​101 CrossRefPubMed
34.
Zurück zum Zitat Kiyose S, Nagura K, Tao H, Igarashi H, Yamada H, Goto M, Maeda M, Kurabe N, Suzuki M, Tsuboi M, Kahyo T, Shinmura K, Hattori N, Sugimura H (2012) Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization. Pathol Int 62(7):477–484. doi:10.1111/j.1440-1827.2012.02832.x CrossRefPubMed Kiyose S, Nagura K, Tao H, Igarashi H, Yamada H, Goto M, Maeda M, Kurabe N, Suzuki M, Tsuboi M, Kahyo T, Shinmura K, Hattori N, Sugimura H (2012) Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization. Pathol Int 62(7):477–484. doi:10.​1111/​j.​1440-1827.​2012.​02832.​x CrossRefPubMed
35.
Zurück zum Zitat Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, Zhang S, Lee M, Wu J, Lim KH, Lei Z, Goh G, Lim QY, Tan AL, Sin Poh DY, Riahi S, Bell S, Shi MM, Linnartz R, Zhu F, Yeoh KG, Toh HC, Yong WP, Cheong HC, Rha SY, Boussioutas A, Grabsch H, Rozen S, Tan P (2012) A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 61(5):673–684. doi:10.1136/gutjnl-2011-301839 PubMedCentralCrossRefPubMed Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, Zhang S, Lee M, Wu J, Lim KH, Lei Z, Goh G, Lim QY, Tan AL, Sin Poh DY, Riahi S, Bell S, Shi MM, Linnartz R, Zhu F, Yeoh KG, Toh HC, Yong WP, Cheong HC, Rha SY, Boussioutas A, Grabsch H, Rozen S, Tan P (2012) A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 61(5):673–684. doi:10.​1136/​gutjnl-2011-301839 PubMedCentralCrossRefPubMed
37.
Zurück zum Zitat Graziano F, Galluccio N, Lorenzini P, Ruzzo A, Canestrari E, D’Emidio S, Catalano V, Sisti V, Ligorio C, Andreoni F, Rulli E, Di Oto E, Fiorentini G, Zingaretti C, De Nictolis M, Cappuzzo F, Magnani M (2011) Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol 29(36):4789–4795. doi:10.1200/JCO.2011.36.7706 CrossRefPubMed Graziano F, Galluccio N, Lorenzini P, Ruzzo A, Canestrari E, D’Emidio S, Catalano V, Sisti V, Ligorio C, Andreoni F, Rulli E, Di Oto E, Fiorentini G, Zingaretti C, De Nictolis M, Cappuzzo F, Magnani M (2011) Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol 29(36):4789–4795. doi:10.​1200/​JCO.​2011.​36.​7706 CrossRefPubMed
38.
Zurück zum Zitat Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, Zamboli A, De Vita F, Galizia G (2008) Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol 15(1):69–79. doi:10.1245/s10434-007-9596-0 CrossRefPubMed Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, Zamboli A, De Vita F, Galizia G (2008) Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol 15(1):69–79. doi:10.​1245/​s10434-007-9596-0 CrossRefPubMed
39.
Zurück zum Zitat Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, Temel JS, Schrag D, Bhargava P, Meyerhardt JA, Wolpin BM, Fidias P, Zheng H, Florio S, Regan E, Fuchs CS (2011) A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol 22(6):1367–1373. doi:10.1093/annonc/mdq604 PubMedCentralCrossRefPubMed Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, Temel JS, Schrag D, Bhargava P, Meyerhardt JA, Wolpin BM, Fidias P, Zheng H, Florio S, Regan E, Fuchs CS (2011) A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol 22(6):1367–1373. doi:10.​1093/​annonc/​mdq604 PubMedCentralCrossRefPubMed
40.
Zurück zum Zitat Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Gotte H, Melezinkova H, Moehler M, Arbeitsgemeinschaft Internistische O, Investigators E (2013) Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 14(6):490–499. doi:10.1016/S1470-2045(13)70102-5 CrossRefPubMed Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Gotte H, Melezinkova H, Moehler M, Arbeitsgemeinschaft Internistische O, Investigators E (2013) Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 14(6):490–499. doi:10.​1016/​S1470-2045(13)70102-5 CrossRefPubMed
41.
Zurück zum Zitat Okines AF, Ashley SE, Cunningham D, Oates J, Turner A, Webb J, Saffery C, Chua YJ, Chau I (2010) Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial. J Clin Oncol 28(25):3945–3950. doi:10.1200/JCO.2010.29.2847 CrossRefPubMed Okines AF, Ashley SE, Cunningham D, Oates J, Turner A, Webb J, Saffery C, Chua YJ, Chau I (2010) Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial. J Clin Oncol 28(25):3945–3950. doi:10.​1200/​JCO.​2010.​29.​2847 CrossRefPubMed
42.
Zurück zum Zitat Luber B, Deplazes J, Keller G, Walch A, Rauser S, Eichmann M, Langer R, Hofler H, Hegewisch-Becker S, Folprecht G, Woll E, Decker T, Endlicher E, Lorenzen S, Fend F, Peschel C, Lordick F (2011) Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). BMC Cancer 11:509. doi:10.1186/1471-2407-11-509 PubMedCentralCrossRefPubMed Luber B, Deplazes J, Keller G, Walch A, Rauser S, Eichmann M, Langer R, Hofler H, Hegewisch-Becker S, Folprecht G, Woll E, Decker T, Endlicher E, Lorenzen S, Fend F, Peschel C, Lordick F (2011) Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). BMC Cancer 11:509. doi:10.​1186/​1471-2407-11-509 PubMedCentralCrossRefPubMed
43.
Zurück zum Zitat Han SW, Oh DY, Im SA, Park SR, Lee KW, Song HS, Lee NS, Lee KH, Choi IS, Lee MH, Kim MA, Kim WH, Bang YJ, Kim TY (2009) Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer. Br J Cancer 100(2):298–304. doi:10.1038/sj.bjc.6604861 PubMedCentralCrossRefPubMed Han SW, Oh DY, Im SA, Park SR, Lee KW, Song HS, Lee NS, Lee KH, Choi IS, Lee MH, Kim MA, Kim WH, Bang YJ, Kim TY (2009) Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer. Br J Cancer 100(2):298–304. doi:10.​1038/​sj.​bjc.​6604861 PubMedCentralCrossRefPubMed
44.
Zurück zum Zitat Moehler M, Mueller A, Trarbach T, Lordick F, Seufferlein T, Kubicka S, Geissler M, Schwarz S, Galle PR, Kanzler S, German Arbeitsgemeinschaft Internistische O (2011) Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol 22(6):1358–1366. doi:10.1093/annonc/mdq591 CrossRefPubMed Moehler M, Mueller A, Trarbach T, Lordick F, Seufferlein T, Kubicka S, Geissler M, Schwarz S, Galle PR, Kanzler S, German Arbeitsgemeinschaft Internistische O (2011) Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol 22(6):1358–1366. doi:10.​1093/​annonc/​mdq591 CrossRefPubMed
45.
Zurück zum Zitat Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Storkel S, Schumacher KM, von Heydebreck A, Celik I, O’Byrne KJ (2012) EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13(1):33–42. doi:10.1016/S1470-2045(11)70318-7 CrossRefPubMed Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Storkel S, Schumacher KM, von Heydebreck A, Celik I, O’Byrne KJ (2012) EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13(1):33–42. doi:10.​1016/​S1470-2045(11)70318-7 CrossRefPubMed
46.
Zurück zum Zitat Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Yanoma S, Noguchi Y (2000) Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma. Cancer Lett 153(1–2):7–12CrossRefPubMed Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Yanoma S, Noguchi Y (2000) Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma. Cancer Lett 153(1–2):7–12CrossRefPubMed
47.
Zurück zum Zitat Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342. doi:10.1056/NEJMoa032691 CrossRefPubMed Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342. doi:10.​1056/​NEJMoa032691 CrossRefPubMed
48.
Zurück zum Zitat Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550. doi:10.1056/NEJMoa061884 CrossRefPubMed Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550. doi:10.​1056/​NEJMoa061884 CrossRefPubMed
49.
Zurück zum Zitat Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29(30):3968–3976. doi:10.1200/JCO.2011.36.2236 CrossRefPubMed Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29(30):3968–3976. doi:10.​1200/​JCO.​2011.​36.​2236 CrossRefPubMed
50.
Zurück zum Zitat Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, Peng Yong W, Langer B, Delmar P, Scherer SJ, Shah MA (2012) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 30(17):2119–2127. doi:10.1200/JCO.2011.39.9824 CrossRefPubMed Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, Peng Yong W, Langer B, Delmar P, Scherer SJ, Shah MA (2012) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 30(17):2119–2127. doi:10.​1200/​JCO.​2011.​39.​9824 CrossRefPubMed
51.
Zurück zum Zitat Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J, for the RTI (2013) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. doi:10.1016/S0140-6736(13)61719-5 Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J, for the RTI (2013) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. doi:10.​1016/​S0140-6736(13)61719-5
52.
Zurück zum Zitat Kilgour E, Su X, Zhan P, Gavine P, Morgan S, Womack C, Jung E-J, Bang Y-J, Im S-A, Kim W, Grabsch H (2012) Prevalence and prognostic significance of FGF receptor 2 (FGFR2) gene amplification in Caucasian and Korean gastric cancer cohorts. J Clin Oncol 30(15_suppl):4124 Kilgour E, Su X, Zhan P, Gavine P, Morgan S, Womack C, Jung E-J, Bang Y-J, Im S-A, Kim W, Grabsch H (2012) Prevalence and prognostic significance of FGF receptor 2 (FGFR2) gene amplification in Caucasian and Korean gastric cancer cohorts. J Clin Oncol 30(15_suppl):4124
54.
Zurück zum Zitat Xie L, Su X, Zhang L, Yin X, Tang L, Zhang X, Xu Y, Gao Z, Liu K, Zhou M, Gao B, Shen D, Zhang L, Ji J, Gavine PR, Zhang J, Kilgour E, Zhang X, Ji Q (2013) FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547. Clin Cancer Res 19(9):2572–2583. doi:10.1158/1078-0432.CCR-12-3898 CrossRefPubMed Xie L, Su X, Zhang L, Yin X, Tang L, Zhang X, Xu Y, Gao Z, Liu K, Zhou M, Gao B, Shen D, Zhang L, Ji J, Gavine PR, Zhang J, Kilgour E, Zhang X, Ji Q (2013) FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547. Clin Cancer Res 19(9):2572–2583. doi:10.​1158/​1078-0432.​CCR-12-3898 CrossRefPubMed
55.
Zurück zum Zitat Lee J, Seo JW, Jun HJ, Ki CS, Park SH, Park YS, Lim HY, Choi MG, Bae JM, Sohn TS, Noh JH, Kim S, Jang HL, Kim JY, Kim KM, Kang WK, Park JO (2011) Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol Rep 25(6):1517–1524. doi:10.3892/or.2011.1219 PubMed Lee J, Seo JW, Jun HJ, Ki CS, Park SH, Park YS, Lim HY, Choi MG, Bae JM, Sohn TS, Noh JH, Kim S, Jang HL, Kim JY, Kim KM, Kang WK, Park JO (2011) Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol Rep 25(6):1517–1524. doi:10.​3892/​or.​2011.​1219 PubMed
56.
Zurück zum Zitat Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, Lauwers GY, Christensen JG, Wilner KD, Haber DA, Salgia R, Bang YJ, Clark JW, Solomon BJ, Iafrate AJ (2011) MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 29(36):4803–4810. doi:10.1200/JCO.2011.35.4928 PubMedCentralCrossRefPubMed Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, Lauwers GY, Christensen JG, Wilner KD, Haber DA, Salgia R, Bang YJ, Clark JW, Solomon BJ, Iafrate AJ (2011) MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 29(36):4803–4810. doi:10.​1200/​JCO.​2011.​35.​4928 PubMedCentralCrossRefPubMed
59.
Zurück zum Zitat Taguchi F, Kodera Y, Katanasaka Y, Yanagihara K, Tamura T, Koizumi F (2011) Efficacy of RAD001 (everolimus) against advanced gastric cancer with peritoneal dissemination. Invest New Drugs 29(6):1198–1205. doi:10.1007/s10637-010-9464-9 CrossRefPubMed Taguchi F, Kodera Y, Katanasaka Y, Yanagihara K, Tamura T, Koizumi F (2011) Efficacy of RAD001 (everolimus) against advanced gastric cancer with peritoneal dissemination. Invest New Drugs 29(6):1198–1205. doi:10.​1007/​s10637-010-9464-9 CrossRefPubMed
60.
Zurück zum Zitat Lang SA, Gaumann A, Koehl GE, Seidel U, Bataille F, Klein D, Ellis LM, Bolder U, Hofstaedter F, Schlitt HJ, Geissler EK, Stoeltzing O (2007) Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120(8):1803–1810. doi:10.1002/ijc.22442 CrossRefPubMed Lang SA, Gaumann A, Koehl GE, Seidel U, Bataille F, Klein D, Ellis LM, Bolder U, Hofstaedter F, Schlitt HJ, Geissler EK, Stoeltzing O (2007) Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120(8):1803–1810. doi:10.​1002/​ijc.​22442 CrossRefPubMed
62.
Zurück zum Zitat Yu G, Wang J, Chen Y, Wang X, Pan J, Li G, Jia Z, Li Q, Yao JC, Xie K (2009) Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of chinese patients with gastric cancer. Clin Cancer Res 15(5):1821–1829. doi:10.1158/1078-0432.CCR-08-2138 CrossRefPubMed Yu G, Wang J, Chen Y, Wang X, Pan J, Li G, Jia Z, Li Q, Yao JC, Xie K (2009) Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of chinese patients with gastric cancer. Clin Cancer Res 15(5):1821–1829. doi:10.​1158/​1078-0432.​CCR-08-2138 CrossRefPubMed
63.
Zurück zum Zitat Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E (2013) Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 Study. J Clin Oncol. doi:10.1200/JCO.2012.48.3552 PubMed Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E (2013) Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 Study. J Clin Oncol. doi:10.​1200/​JCO.​2012.​48.​3552 PubMed
64.
Zurück zum Zitat Yoon DH, Ryu MH, Park YS, Lee HJ, Lee C, Ryoo BY, Lee JL, Chang HM, Kim TW, Kang YK (2012) Phase II study of everolimus with biomarker exploration in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum. Br J Cancer 106(6):1039–1044. doi:10.1038/bjc.2012.47 PubMedCentralCrossRefPubMed Yoon DH, Ryu MH, Park YS, Lee HJ, Lee C, Ryoo BY, Lee JL, Chang HM, Kim TW, Kang YK (2012) Phase II study of everolimus with biomarker exploration in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum. Br J Cancer 106(6):1039–1044. doi:10.​1038/​bjc.​2012.​47 PubMedCentralCrossRefPubMed
65.
Zurück zum Zitat Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304(5670):554. doi:10.1126/science.1096502 CrossRefPubMed Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304(5670):554. doi:10.​1126/​science.​1096502 CrossRefPubMed
66.
Zurück zum Zitat Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S Jr, Duval A, Carneiro F, Machado JC, Hamelin R, Seruca R (2005) The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 41(11):1649–1654. doi:10.1016/j.ejca.2005.04.022 CrossRefPubMed Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S Jr, Duval A, Carneiro F, Machado JC, Hamelin R, Seruca R (2005) The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 41(11):1649–1654. doi:10.​1016/​j.​ejca.​2005.​04.​022 CrossRefPubMed
69.
Zurück zum Zitat Barbi S, Cataldo I, De Manzoni G, Bersani S, Lamba S, Mattuzzi S, Bardelli A, Scarpa A (2010) The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type. J Exp Clin Cancer Res 29:32. doi:10.1186/1756-9966-29-32 PubMedCentralCrossRefPubMed Barbi S, Cataldo I, De Manzoni G, Bersani S, Lamba S, Mattuzzi S, Bardelli A, Scarpa A (2010) The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type. J Exp Clin Cancer Res 29:32. doi:10.​1186/​1756-9966-29-32 PubMedCentralCrossRefPubMed
70.
Zurück zum Zitat Mueller A, Bachmann E, Linnig M, Khillimberger K, Schimanski CC, Galle PR, Moehler M (2012) Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines. Cancer Chemother Pharmacol 69(6):1601–1615. doi:10.1007/s00280-012-1869-z CrossRefPubMed Mueller A, Bachmann E, Linnig M, Khillimberger K, Schimanski CC, Galle PR, Moehler M (2012) Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines. Cancer Chemother Pharmacol 69(6):1601–1615. doi:10.​1007/​s00280-012-1869-z CrossRefPubMed
71.
Zurück zum Zitat Pinto M, Oliveira C, Machado JC, Cirnes L, Tavares J, Carneiro F, Hamelin R, Hofstra R, Seruca R, Sobrinho-Simoes M (2000) MSI-L gastric carcinomas share the hMLH1 methylation status of MSI-H carcinomas but not their clinicopathological profile. Lab Invest 80(12):1915–1923CrossRefPubMed Pinto M, Oliveira C, Machado JC, Cirnes L, Tavares J, Carneiro F, Hamelin R, Hofstra R, Seruca R, Sobrinho-Simoes M (2000) MSI-L gastric carcinomas share the hMLH1 methylation status of MSI-H carcinomas but not their clinicopathological profile. Lab Invest 80(12):1915–1923CrossRefPubMed
72.
Zurück zum Zitat Corso G, Velho S, Paredes J, Pedrazzani C, Martins D, Milanezi F, Pascale V, Vindigni C, Pinheiro H, Leite M, Marrelli D, Sousa S, Carneiro F, Oliveira C, Roviello F, Seruca R (2011) Oncogenic mutations in gastric cancer with microsatellite instability. Eur J Cancer 47(3):443–451. doi:10.1016/j.ejca.2010.09.008 CrossRefPubMed Corso G, Velho S, Paredes J, Pedrazzani C, Martins D, Milanezi F, Pascale V, Vindigni C, Pinheiro H, Leite M, Marrelli D, Sousa S, Carneiro F, Oliveira C, Roviello F, Seruca R (2011) Oncogenic mutations in gastric cancer with microsatellite instability. Eur J Cancer 47(3):443–451. doi:10.​1016/​j.​ejca.​2010.​09.​008 CrossRefPubMed
73.
Zurück zum Zitat Oliveira C, Seruca R, Seixas M, Sobrinho-Simoes M (1998) The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different “target genes”: a study of the TGFbeta RII, IGFII R, and BAX genes. Am J Pathol 153(4):1211–1219PubMedCentralCrossRefPubMed Oliveira C, Seruca R, Seixas M, Sobrinho-Simoes M (1998) The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different “target genes”: a study of the TGFbeta RII, IGFII R, and BAX genes. Am J Pathol 153(4):1211–1219PubMedCentralCrossRefPubMed
74.
Zurück zum Zitat Oliveira C, Pinto M, Duval A, Brennetot C, Domingo E, Espin E, Armengol M, Yamamoto H, Hamelin R, Seruca R, Schwartz S Jr (2003) BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene 22(57):9192–9196. doi:10.1038/sj.onc.1207061 CrossRefPubMed Oliveira C, Pinto M, Duval A, Brennetot C, Domingo E, Espin E, Armengol M, Yamamoto H, Hamelin R, Seruca R, Schwartz S Jr (2003) BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene 22(57):9192–9196. doi:10.​1038/​sj.​onc.​1207061 CrossRefPubMed
75.
Zurück zum Zitat van Grieken NC, Aoyma T, Chambers PA, Bottomley D, Ward LC, Inam I, Buffart TE, Das K, Lim T, Pang B, Zhang SL, Tan IB, Carvalho B, Heideman DA, Miyagi Y, Kameda Y, Arai T, Meijer GA, Tsuburaya A, Tan P, Yoshikawa T, Grabsch HI (2013) KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study. Br J Cancer 108(7):1495–1501. doi:10.1038/bjc.2013.109 CrossRefPubMed van Grieken NC, Aoyma T, Chambers PA, Bottomley D, Ward LC, Inam I, Buffart TE, Das K, Lim T, Pang B, Zhang SL, Tan IB, Carvalho B, Heideman DA, Miyagi Y, Kameda Y, Arai T, Meijer GA, Tsuburaya A, Tan P, Yoshikawa T, Grabsch HI (2013) KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study. Br J Cancer 108(7):1495–1501. doi:10.​1038/​bjc.​2013.​109 CrossRefPubMed
76.
Zurück zum Zitat Brennetot C, Duval A, Hamelin R, Pinto M, Oliveira C, Seruca R, Schwartz S Jr (2003) Frequent Ki-ras mutations in gastric tumors of the MSI phenotype. Gastroenterology 125(4):1282CrossRefPubMed Brennetot C, Duval A, Hamelin R, Pinto M, Oliveira C, Seruca R, Schwartz S Jr (2003) Frequent Ki-ras mutations in gastric tumors of the MSI phenotype. Gastroenterology 125(4):1282CrossRefPubMed
77.
Zurück zum Zitat Warneke VS, Behrens HM, Haag J, Balschun K, Boger C, Becker T, Ebert MP, Lordick F, Rocken C (2013) Prognostic and putative predictive biomarkers of gastric cancer for personalized medicine. Diagn Mol Pathol 22(3):127–137. doi:10.1097/PDM.0b013e318284188e CrossRefPubMed Warneke VS, Behrens HM, Haag J, Balschun K, Boger C, Becker T, Ebert MP, Lordick F, Rocken C (2013) Prognostic and putative predictive biomarkers of gastric cancer for personalized medicine. Diagn Mol Pathol 22(3):127–137. doi:10.​1097/​PDM.​0b013e318284188e​ CrossRefPubMed
78.
Zurück zum Zitat Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634. doi:10.1200/JCO.2007.14.7116 CrossRefPubMed Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634. doi:10.​1200/​JCO.​2007.​14.​7116 CrossRefPubMed
79.
Zurück zum Zitat Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765. doi:10.1056/NEJMoa0804385 CrossRefPubMed Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765. doi:10.​1056/​NEJMoa0804385 CrossRefPubMed
80.
Zurück zum Zitat Wittinghofer A, Scheffzek K, Ahmadian MR (1997) The interaction of Ras with GTPase-activating proteins. FEBS Lett 410(1):63–67CrossRefPubMed Wittinghofer A, Scheffzek K, Ahmadian MR (1997) The interaction of Ras with GTPase-activating proteins. FEBS Lett 410(1):63–67CrossRefPubMed
81.
Zurück zum Zitat Carvalho J, van Grieken NC, Pereira PM, Sousa S, Tijssen M, Buffart TE, Diosdado B, Grabsch H, Santos MA, Meijer G, Seruca R, Carvalho B, Oliveira C (2012) Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer. J Pathol 228(1):31–44. doi:10.1002/path.4032 PubMed Carvalho J, van Grieken NC, Pereira PM, Sousa S, Tijssen M, Buffart TE, Diosdado B, Grabsch H, Santos MA, Meijer G, Seruca R, Carvalho B, Oliveira C (2012) Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer. J Pathol 228(1):31–44. doi:10.​1002/​path.​4032 PubMed
82.
Zurück zum Zitat Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, Roviello F, Oliveira C (2013) Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol 31(7):868–875. doi:10.1200/JCO.2012.44.4612 CrossRefPubMed Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R, Roviello F, Oliveira C (2013) Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol 31(7):868–875. doi:10.​1200/​JCO.​2012.​44.​4612 CrossRefPubMed
83.
Zurück zum Zitat Ferreira P, Oliveira MJ, Beraldi E, Mateus AR, Nakajima T, Gleave M, Yokota J, Carneiro F, Huntsman D, Seruca R, Suriano G (2005) Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro. Exp Cell Res 310(1):99–104. doi:10.1016/j.yexcr.2005.07.010 CrossRefPubMed Ferreira P, Oliveira MJ, Beraldi E, Mateus AR, Nakajima T, Gleave M, Yokota J, Carneiro F, Huntsman D, Seruca R, Suriano G (2005) Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro. Exp Cell Res 310(1):99–104. doi:10.​1016/​j.​yexcr.​2005.​07.​010 CrossRefPubMed
84.
Zurück zum Zitat Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L, Helfrich B, Dziadziuszko R, Chan DC, Sugita M, Chan Z, Baron A, Franklin W, Drabkin HA, Girard L, Gazdar AF, Minna JD, Bunn PA Jr (2006) Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 66(2):944–950. doi:10.1158/0008-5472.CAN-05-1988 CrossRefPubMed Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L, Helfrich B, Dziadziuszko R, Chan DC, Sugita M, Chan Z, Baron A, Franklin W, Drabkin HA, Girard L, Gazdar AF, Minna JD, Bunn PA Jr (2006) Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 66(2):944–950. doi:10.​1158/​0008-5472.​CAN-05-1988 CrossRefPubMed
85.
Zurück zum Zitat Xin HW, Yang JH, Nguyen DM (2013) Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor requires E-cadherin in esophageal cancer and malignant pleural mesothelioma. Anticancer Res 33(6):2401–2408PubMed Xin HW, Yang JH, Nguyen DM (2013) Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor requires E-cadherin in esophageal cancer and malignant pleural mesothelioma. Anticancer Res 33(6):2401–2408PubMed
86.
Zurück zum Zitat Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, Wu KC, Wu DC, Sollano J, Kachintorn U, Gotoda T, Lin JT, You WC, Ng EK, Sung JJ, Asia Pacific Working Group on Gastric C (2008) Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol 9(3):279–287. doi:10.1016/S1470-2045(08)70072-X CrossRefPubMed Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, Wu KC, Wu DC, Sollano J, Kachintorn U, Gotoda T, Lin JT, You WC, Ng EK, Sung JJ, Asia Pacific Working Group on Gastric C (2008) Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol 9(3):279–287. doi:10.​1016/​S1470-2045(08)70072-X CrossRefPubMed
87.
Zurück zum Zitat Thekkek N, Muldoon T, Polydorides AD, Maru DM, Harpaz N, Harris MT, Hofstettor W, Hiotis SP, Kim SA, Ky AJ, Anandasabapathy S, Richards-Kortum R (2012) Vital-dye enhanced fluorescence imaging of GI mucosa: metaplasia, neoplasia, inflammation. Gastrointest Endosc 75(4):877–887. doi:10.1016/j.gie.2011.10.004 PubMedCentralCrossRefPubMed Thekkek N, Muldoon T, Polydorides AD, Maru DM, Harpaz N, Harris MT, Hofstettor W, Hiotis SP, Kim SA, Ky AJ, Anandasabapathy S, Richards-Kortum R (2012) Vital-dye enhanced fluorescence imaging of GI mucosa: metaplasia, neoplasia, inflammation. Gastrointest Endosc 75(4):877–887. doi:10.​1016/​j.​gie.​2011.​10.​004 PubMedCentralCrossRefPubMed
89.
Zurück zum Zitat Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, Seruca R, Iacopetta B, Hamelin R (2002) Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123(6):1804–1811. doi:10.1053/gast.2002.37070 CrossRefPubMed Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, Seruca R, Iacopetta B, Hamelin R (2002) Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123(6):1804–1811. doi:10.​1053/​gast.​2002.​37070 CrossRefPubMed
Metadaten
Titel
Biomarkers for gastric cancer: prognostic, predictive or targets of therapy?
verfasst von
Cecília Durães
Gabriela M. Almeida
Raquel Seruca
Carla Oliveira
Fátima Carneiro
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 3/2014
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-013-1533-y

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