Skip to main content
Erschienen in: Tumor Biology 6/2011

01.12.2011 | Research Article

Prognostic impact of vascular endothelial growth factor-A expression in resected gallbladder carcinoma

verfasst von: Xiao-Nan Sun, Wei-Guo Cao, Xin Wang, Qi Wang, Ben-Xing Gu, Qi-Chu Yang, Jian-Bin Hu, Hai Liu, Shu Zheng

Erschienen in: Tumor Biology | Ausgabe 6/2011

Einloggen, um Zugang zu erhalten

Abstract

The purpose of this study was to evaluate the value of vascular endothelial growth factor-A (VEGF-A) expression and other confirmed prognostic factors in predicting clinical outcomes after the resection of gallbladder carcinoma (GBC). Between January 1999 and January 2006, a total of 84 consecutive and non-selected patients who underwent resection for GBC were retrospectively reviewed. Of the 84 patients studied, 45 cases (53.6%) exhibited high expression of VEGF-A and were placed into the high expression group. The 14 cases (16.7%) that showed no VEGF expression and the 25 cases (29.7%) that had lower VEGF-A levels were pooled into the low expression group (46.4%). There was a relationship between VEGF-A status and pM stage (P = 0.027) as well as histologic differentiation (P < 0.001). In univariate analysis by log-rank test, ECOG performance status, CA 19-9, pN stage, pM stage, histologic differentiation, and VEGF-A expression were significant prognostic factors (P = 0.015, 0.001, 0.020, <0.001, 0.040, and <0.001, respectively). Multivariate analysis revealed that pN status and VEGF-A expression maintained independent prognostic influence on overall survival (P < 0.001 and P = 0.013, respectively). VEGF-A expression has a positive correlation with pM stage and histologic differentiation. pN status and VEGF-A expression were independent prognostic factors of overall survival in patients with resected GBC.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef
2.
Zurück zum Zitat Furuse J. Postoperative adjuvant treatments for biliary tract cancer. J Hepatobiliary Pancreat Surg. 2008;15:463–7.PubMedCrossRef Furuse J. Postoperative adjuvant treatments for biliary tract cancer. J Hepatobiliary Pancreat Surg. 2008;15:463–7.PubMedCrossRef
3.
Zurück zum Zitat de Aretxabala X, Roa I, Berrios M, Hepp J, Gallardo J, Cordova A, et al. Chemoradiotherapy in gallbladder cancer. J Surg Oncol. 2006;93:699–704.PubMedCrossRef de Aretxabala X, Roa I, Berrios M, Hepp J, Gallardo J, Cordova A, et al. Chemoradiotherapy in gallbladder cancer. J Surg Oncol. 2006;93:699–704.PubMedCrossRef
4.
Zurück zum Zitat Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol. 2008;98:485–9.PubMedCrossRef Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol. 2008;98:485–9.PubMedCrossRef
5.
Zurück zum Zitat Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. 2004;8:183–90.PubMedCrossRef Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. 2004;8:183–90.PubMedCrossRef
6.
Zurück zum Zitat Gold DG, Miller RC, Haddock MG, Gunderson LL, Quevedo F, Donohue JH, et al. Adjuvant therapy for gallbladder carcinoma: the Mayo clinic experience. Int J Radiat Oncol Biol Phys. 2009;75:150–5.PubMedCrossRef Gold DG, Miller RC, Haddock MG, Gunderson LL, Quevedo F, Donohue JH, et al. Adjuvant therapy for gallbladder carcinoma: the Mayo clinic experience. Int J Radiat Oncol Biol Phys. 2009;75:150–5.PubMedCrossRef
7.
Zurück zum Zitat Cho SY, Kim SH, Park SJ, Han SS, Kim YK, Lee KW, et al. Adjuvant chemoradiation therapy in gallbladder cancer. J Surg Oncol. 2010;102:87–93.PubMedCrossRef Cho SY, Kim SH, Park SJ, Han SS, Kim YK, Lee KW, et al. Adjuvant chemoradiation therapy in gallbladder cancer. J Surg Oncol. 2010;102:87–93.PubMedCrossRef
8.
Zurück zum Zitat Murakami Y, Uemura K, Hayasidani Y, Sudo T, Hashimoto Y, Ohge H, et al. Indication for postoperative adjuvant therapy in biliary carcinoma based on analysis of recurrence and survival after surgical resection. Dig Dis Sci. 2009;54:1360–4.PubMedCrossRef Murakami Y, Uemura K, Hayasidani Y, Sudo T, Hashimoto Y, Ohge H, et al. Indication for postoperative adjuvant therapy in biliary carcinoma based on analysis of recurrence and survival after surgical resection. Dig Dis Sci. 2009;54:1360–4.PubMedCrossRef
9.
Zurück zum Zitat Katkoori VR, Suarez-Cuervo C, Shanmugam C, Jhala Nirag C, Callens T, Messiaen L, et al. Bax expression is a candidate prognostic and predictive marker of colorectal cancer. J Gastrointest Oncol. 2010;1:76–89. Katkoori VR, Suarez-Cuervo C, Shanmugam C, Jhala Nirag C, Callens T, Messiaen L, et al. Bax expression is a candidate prognostic and predictive marker of colorectal cancer. J Gastrointest Oncol. 2010;1:76–89.
10.
Zurück zum Zitat Quan ZW, Wu K, Wang J, Shi W, Zhang Z, Merrell RC. Association of p53, p16, and vascular endothelial growth factor protein expressions with the prognosis and metastasis of gallbladder cancer. J Am Coll Surg. 2001;193:380–3.PubMedCrossRef Quan ZW, Wu K, Wang J, Shi W, Zhang Z, Merrell RC. Association of p53, p16, and vascular endothelial growth factor protein expressions with the prognosis and metastasis of gallbladder cancer. J Am Coll Surg. 2001;193:380–3.PubMedCrossRef
11.
Zurück zum Zitat Giatromanolaki A, Koukourakis MI, Simopoulos C, Polychronidis A, Sivridis E. Vascular endothelial growth factor (VEGF) expression in operable gallbladder carcinomas. Eur J Surg Oncol. 2003;29:879–83.PubMedCrossRef Giatromanolaki A, Koukourakis MI, Simopoulos C, Polychronidis A, Sivridis E. Vascular endothelial growth factor (VEGF) expression in operable gallbladder carcinomas. Eur J Surg Oncol. 2003;29:879–83.PubMedCrossRef
12.
Zurück zum Zitat Giatromanolaki A, Sivridis E, Simopoulos C, Polychronidis A, Gatter KC, Harris AL, et al. Hypoxia inducible factors 1alpha and 2alpha are associated with VEGF expression and angiogenesis in gallbladder carcinomas. J Surg Oncol. 2006;94:242–7.PubMedCrossRef Giatromanolaki A, Sivridis E, Simopoulos C, Polychronidis A, Gatter KC, Harris AL, et al. Hypoxia inducible factors 1alpha and 2alpha are associated with VEGF expression and angiogenesis in gallbladder carcinomas. J Surg Oncol. 2006;94:242–7.PubMedCrossRef
13.
Zurück zum Zitat Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.PubMedCrossRef Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.PubMedCrossRef
14.
Zurück zum Zitat Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–27.PubMedCrossRef Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–27.PubMedCrossRef
15.
Zurück zum Zitat Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–39.PubMed Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–39.PubMed
16.
Zurück zum Zitat Okita S, Kondoh S, Shiraishi K, Kaino S, Hatano S, Okita K. Expression of vascular endothelial growth factor correlates with tumor progression in gallbladder cancer. Int J Oncol. 1998;12:1013–8.PubMed Okita S, Kondoh S, Shiraishi K, Kaino S, Hatano S, Okita K. Expression of vascular endothelial growth factor correlates with tumor progression in gallbladder cancer. Int J Oncol. 1998;12:1013–8.PubMed
17.
Zurück zum Zitat Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, Morrow M (eds) (2002). American Joint Committee on Cancer Staging Manual. 6th ed. Springer, New York 139–144 Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, Morrow M (eds) (2002). American Joint Committee on Cancer Staging Manual. 6th ed. Springer, New York 139–144
18.
Zurück zum Zitat Kokudo N, Makuuchi M, Natori T, Sakamoto Y, Yamamoto J, Seki M, et al. Strategies for surgical treatment of gallbladder carcinoma based on information available before resection. Arch Surg. 2003;138:741–50.PubMedCrossRef Kokudo N, Makuuchi M, Natori T, Sakamoto Y, Yamamoto J, Seki M, et al. Strategies for surgical treatment of gallbladder carcinoma based on information available before resection. Arch Surg. 2003;138:741–50.PubMedCrossRef
19.
Zurück zum Zitat Tsukada K, Kurosaki I, Uchida K, Shirai Y, Oohashi Y, Yokoyama N, et al. Lymph node spread from carcinoma of the gallbladder. Cancer. 1997;80:661–7.PubMedCrossRef Tsukada K, Kurosaki I, Uchida K, Shirai Y, Oohashi Y, Yokoyama N, et al. Lymph node spread from carcinoma of the gallbladder. Cancer. 1997;80:661–7.PubMedCrossRef
20.
Zurück zum Zitat Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, et al. Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas. Anticancer Res. 1999;19:2257–60.PubMed Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, et al. Vascular endothelial growth factor expression is an independent negative predictor in extrahepatic biliary tract carcinomas. Anticancer Res. 1999;19:2257–60.PubMed
21.
Zurück zum Zitat Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL. Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol. 1995;177:275–83.PubMedCrossRef Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL. Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol. 1995;177:275–83.PubMedCrossRef
22.
Zurück zum Zitat Volm M, Koomägi R, Mattern J. Interrelationships between microvessel density, expression of VEGF and resistance to doxorubicin of non-small lung cell carcinoma. Anticancer Res. 1996;16:213–7.PubMed Volm M, Koomägi R, Mattern J. Interrelationships between microvessel density, expression of VEGF and resistance to doxorubicin of non-small lung cell carcinoma. Anticancer Res. 1996;16:213–7.PubMed
23.
Zurück zum Zitat Giatromanolaki A, Koukourakis MI, Kakolyris S, Turley H, O’Byrne K, Scott PA, et al. Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer. Clin Cancer Res. 1998;4:3017–24.PubMed Giatromanolaki A, Koukourakis MI, Kakolyris S, Turley H, O’Byrne K, Scott PA, et al. Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer. Clin Cancer Res. 1998;4:3017–24.PubMed
24.
Zurück zum Zitat Koukourakis MI, Giatromanolaki A, Thorpe PE, Brekken RA, Sivridis E, Kakolyris S, et al. Vascular endothelial growth factor/KDR activated microvessel density versus CD31 standard microvessel density in non-small cell lung cancer. Cancer Res. 2000;60:3088–95.PubMed Koukourakis MI, Giatromanolaki A, Thorpe PE, Brekken RA, Sivridis E, Kakolyris S, et al. Vascular endothelial growth factor/KDR activated microvessel density versus CD31 standard microvessel density in non-small cell lung cancer. Cancer Res. 2000;60:3088–95.PubMed
25.
Zurück zum Zitat Amaya H, Tanigawa N, Lu C, Matsumura M, Shimomatsuya T, Horiuchi T, et al. Association of vascular endothelial growth factor expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet -derived endothelial cell growth factor expression in human colorectal cancer. Cancer Lett. 1997;119:227–35.PubMedCrossRef Amaya H, Tanigawa N, Lu C, Matsumura M, Shimomatsuya T, Horiuchi T, et al. Association of vascular endothelial growth factor expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet -derived endothelial cell growth factor expression in human colorectal cancer. Cancer Lett. 1997;119:227–35.PubMedCrossRef
26.
Zurück zum Zitat Maeda K, Kang SM, Ogawa M, Onoda N, Sawada T, Nakata B, et al. Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma. Int J Cancer. 1997;74:545–50.PubMedCrossRef Maeda K, Kang SM, Ogawa M, Onoda N, Sawada T, Nakata B, et al. Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma. Int J Cancer. 1997;74:545–50.PubMedCrossRef
27.
Zurück zum Zitat Takahashi Y, Bucana CD, Akagi Y, Liu W, Cleary KR, Mai M, et al. Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer. Clin Cancer Res. 1998;4:429–34.PubMed Takahashi Y, Bucana CD, Akagi Y, Liu W, Cleary KR, Mai M, et al. Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer. Clin Cancer Res. 1998;4:429–34.PubMed
28.
Zurück zum Zitat Ikeda N, Adachi M, Taki T, Huang C, Hashida H, Takabayashi A, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer. 1999;79:1553–63.PubMedCrossRef Ikeda N, Adachi M, Taki T, Huang C, Hashida H, Takabayashi A, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer. 1999;79:1553–63.PubMedCrossRef
29.
Zurück zum Zitat Seki S, Fujiwara M, Matsuura M, Fujita S, Ikeda H, Asahina I, et al. Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors. Oral Oncol. 2011;47:588–93.PubMedCrossRef Seki S, Fujiwara M, Matsuura M, Fujita S, Ikeda H, Asahina I, et al. Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors. Oral Oncol. 2011;47:588–93.PubMedCrossRef
30.
Zurück zum Zitat Bartlett DL, Fong Y, Fortner JG, Brennan MF, Blumgart LH. Long-term results after resection for gallbladder cancer. Implications for staging and management. Ann Surg. 1996;224:639–46.PubMedCrossRef Bartlett DL, Fong Y, Fortner JG, Brennan MF, Blumgart LH. Long-term results after resection for gallbladder cancer. Implications for staging and management. Ann Surg. 1996;224:639–46.PubMedCrossRef
31.
Zurück zum Zitat Yamaguchi K, Nagino M, Oda K, Kamiya K, Uesaka K, Nimura Y. Perineural invasion has a negative impact on survival of patients with gallbladder cancer. Br J Surg. 2002;89:1130–6.PubMedCrossRef Yamaguchi K, Nagino M, Oda K, Kamiya K, Uesaka K, Nimura Y. Perineural invasion has a negative impact on survival of patients with gallbladder cancer. Br J Surg. 2002;89:1130–6.PubMedCrossRef
32.
Zurück zum Zitat Fong Y, Jamagin W, Blumgart LH. Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg. 2000;232:557–69.PubMedCrossRef Fong Y, Jamagin W, Blumgart LH. Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg. 2000;232:557–69.PubMedCrossRef
33.
Zurück zum Zitat Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4:695–706.PubMedCrossRef Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4:695–706.PubMedCrossRef
34.
Zurück zum Zitat Kayahara M, Nagakawa T, Nakagawara H, Kitagawa H, Ohta T. Prognostic factors for gallbladder cancer in Japan. Ann Surg. 2008;248:807–14.PubMedCrossRef Kayahara M, Nagakawa T, Nakagawara H, Kitagawa H, Ohta T. Prognostic factors for gallbladder cancer in Japan. Ann Surg. 2008;248:807–14.PubMedCrossRef
35.
Zurück zum Zitat Lowenfels AB. Gallstones and glaciers: the stone that came in from the cold. Lancet. 1988;18:1385–6.CrossRef Lowenfels AB. Gallstones and glaciers: the stone that came in from the cold. Lancet. 1988;18:1385–6.CrossRef
36.
Zurück zum Zitat Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology. 1999;46:1529–32.PubMed Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology. 1999;46:1529–32.PubMed
37.
Zurück zum Zitat Liu Y, Qiu Y, Zhang X, Tian Y, Huang D, Zhou X, et al. The expression and correlation of HMGB1 and VEGF protein in laryngeal squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011;25:265–9.PubMed Liu Y, Qiu Y, Zhang X, Tian Y, Huang D, Zhou X, et al. The expression and correlation of HMGB1 and VEGF protein in laryngeal squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011;25:265–9.PubMed
38.
Zurück zum Zitat Czito BG, Hurwitz HI, Clough RW, Tyler DS, Morse MA, Clary BM, et al. Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys. 2005;62:1030–4.PubMedCrossRef Czito BG, Hurwitz HI, Clough RW, Tyler DS, Morse MA, Clary BM, et al. Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys. 2005;62:1030–4.PubMedCrossRef
39.
Zurück zum Zitat Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H, et al. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys. 2002;52:167–75.PubMedCrossRef Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H, et al. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys. 2002;52:167–75.PubMedCrossRef
Metadaten
Titel
Prognostic impact of vascular endothelial growth factor-A expression in resected gallbladder carcinoma
verfasst von
Xiao-Nan Sun
Wei-Guo Cao
Xin Wang
Qi Wang
Ben-Xing Gu
Qi-Chu Yang
Jian-Bin Hu
Hai Liu
Shu Zheng
Publikationsdatum
01.12.2011
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2011
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0221-2

Weitere Artikel der Ausgabe 6/2011

Tumor Biology 6/2011 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.