Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 2/2012

01.02.2012 | Mini Review

Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer

verfasst von: Jan Nyrop Jakobsen, Jens Benn Sørensen

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Biomarker expression is increasingly being used to customize treatment in non-small cell lung cancer (NSCLC). The choice of systemic treatment usually depends on biomarker expression in the initial diagnostic biopsy taken before initiation of first-line treatment. Chemotherapy induces DNA damages in the tumor cells, and thus, biomarker expression in the tumor after systemic treatment might not be identical to biomarker expression in the diagnostic biopsy. NSCLC is highly heterogeneous and biomarker expression may vary in different areas within the same tumor. This review explores the tumor heterogeneity and chemotherapy-induced changes in EGFR biomarker status in NSCLC.

Methods

A literature search was performed in August 2011 using pubmed.

Results

Fifteen trials explored EGFR status in primary tumor and subsequent resected primary tumor, lymph node metastases, or organ metastases. Four papers compared EGFR status in primary tumor or metastases before and after systemic treatment. All trials included relatively few patients and used different chemotherapy regimes, biopsy locations, or time intervals between biopsies.

Conclusions

Tumor heterogeneity and probably also previous systemic treatment may be an obstacle for correct interpretation of EGFR status in NSCLC. Heterogeneity regarding EGFR mutations is probably rare and previously reported intra and intertumor heterogeneity may be due to methodological issues. In the current and future clinical scenario with many different options for systemic treatment both as 2nd line and beyond, it is increasingly important to further elucidate the role extent of chemotherapy-induced changes in biomarker expression for proper use of biomarkers in order to customize treatment and thus improve prognosis.
Literatur
1.
Zurück zum Zitat United States Cancer Statistics 2002–2004 (2007) Incidence and Mortality Web-based Report Version. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute. J Nat Cancer Inst United States Cancer Statistics 2002–2004 (2007) Incidence and Mortality Web-based Report Version. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute. J Nat Cancer Inst
2.
Zurück zum Zitat Taron M, Ichinose Y, Rosell R, Mok T, Massuti B, Zamora L et al (2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res 11(16):5878–5885PubMedCrossRef Taron M, Ichinose Y, Rosell R, Mok T, Massuti B, Zamora L et al (2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res 11(16):5878–5885PubMedCrossRef
3.
Zurück zum Zitat Vilmar AC, Sorensen JB (2011) Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives. Eur Respir Rev: An Off J Eur Respir Soc 20(119):45–52 Vilmar AC, Sorensen JB (2011) Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives. Eur Respir Rev: An Off J Eur Respir Soc 20(119):45–52
4.
Zurück zum Zitat Coghlin C, Murray GI (2010) Current and emerging concepts in tumour metastasis. J Pathol 222(1):1–15PubMedCrossRef Coghlin C, Murray GI (2010) Current and emerging concepts in tumour metastasis. J Pathol 222(1):1–15PubMedCrossRef
6.
Zurück zum Zitat Fong KM, Sekido Y, Gazdar AF, Minna JD (2003) Lung cancer. 9: molecular biology of lung cancer: clinical implications. Thorax 58(10):892–900PubMedCrossRef Fong KM, Sekido Y, Gazdar AF, Minna JD (2003) Lung cancer. 9: molecular biology of lung cancer: clinical implications. Thorax 58(10):892–900PubMedCrossRef
7.
Zurück zum Zitat Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97(5):339–346PubMedCrossRef Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97(5):339–346PubMedCrossRef
8.
Zurück zum Zitat Sekido Y, Fong KM, Minna JD (2003) Molecular genetics of lung cancer. Annu Rev Med 54:73–87PubMedCrossRef Sekido Y, Fong KM, Minna JD (2003) Molecular genetics of lung cancer. Annu Rev Med 54:73–87PubMedCrossRef
9.
Zurück zum Zitat Prudkin L, Wistuba II (2006) Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications. Ann Diagn Pathol 10(5):306–315PubMedCrossRef Prudkin L, Wistuba II (2006) Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications. Ann Diagn Pathol 10(5):306–315PubMedCrossRef
10.
Zurück zum Zitat Tokumo M, Toyooka S, Kiura K, Shigematsu H, Tomii K, Aoe M et al (2005) The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res 11(3):1167–1173PubMed Tokumo M, Toyooka S, Kiura K, Shigematsu H, Tomii K, Aoe M et al (2005) The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res 11(3):1167–1173PubMed
11.
Zurück zum Zitat Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101(36):13306–13311PubMedCrossRef Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101(36):13306–13311PubMedCrossRef
12.
Zurück zum Zitat Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139PubMedCrossRef Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139PubMedCrossRef
13.
Zurück zum Zitat Milas I, Komaki R, Hachiya T, Bubb RS, Ro JY, Langford L et al (2003) Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases. Clin Cancer Res 9(3):1070–1076PubMed Milas I, Komaki R, Hachiya T, Bubb RS, Ro JY, Langford L et al (2003) Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases. Clin Cancer Res 9(3):1070–1076PubMed
14.
Zurück zum Zitat Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerlock P et al (2005) Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a southwest oncology group study. J Clin Oncol 23(28):6838–6845PubMedCrossRef Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerlock P et al (2005) Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a southwest oncology group study. J Clin Oncol 23(28):6838–6845PubMedCrossRef
15.
Zurück zum Zitat Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L et al (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Nat Cancer Inst 97(9):643–655PubMedCrossRef Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L et al (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Nat Cancer Inst 97(9):643–655PubMedCrossRef
16.
Zurück zum Zitat Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMedCrossRef Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMedCrossRef
17.
Zurück zum Zitat van Zandwijk N, Mathy A, Boerrigter L, Ruijter H, Tielen I, de Jong D et al (2007) EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer. Ann Oncol 18(1):99–103PubMedCrossRef van Zandwijk N, Mathy A, Boerrigter L, Ruijter H, Tielen I, de Jong D et al (2007) EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer. Ann Oncol 18(1):99–103PubMedCrossRef
18.
Zurück zum Zitat Yoshida K, Yatabe Y, Park JY, Shimizu J, Horio Y, Matsuo K et al (2007) Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer. J Thorac Oncol 2(1):22–28PubMedCrossRef Yoshida K, Yatabe Y, Park JY, Shimizu J, Horio Y, Matsuo K et al (2007) Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer. J Thorac Oncol 2(1):22–28PubMedCrossRef
19.
Zurück zum Zitat Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957PubMedCrossRef Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957PubMedCrossRef
20.
Zurück zum Zitat Yoo SB, Chung JH, Lee HJ, Lee CT, Jheon S, Sung SW et al (2010) Epidermal growth factor receptor mutation and p53 overexpression during the multistage progression of small adenocarcinoma of the lung. J Thorac Oncol 5(7):964–969PubMed Yoo SB, Chung JH, Lee HJ, Lee CT, Jheon S, Sung SW et al (2010) Epidermal growth factor receptor mutation and p53 overexpression during the multistage progression of small adenocarcinoma of the lung. J Thorac Oncol 5(7):964–969PubMed
21.
Zurück zum Zitat Dacic S, Flanagan M, Cieply K, Ramalingam S, Luketich J, Belani C et al (2006) Significance of EGFR protein expression and gene amplification in non-small cell lung carcinoma. Am J Clin Pathol 125(6):860–865PubMedCrossRef Dacic S, Flanagan M, Cieply K, Ramalingam S, Luketich J, Belani C et al (2006) Significance of EGFR protein expression and gene amplification in non-small cell lung carcinoma. Am J Clin Pathol 125(6):860–865PubMedCrossRef
22.
Zurück zum Zitat Takano T, Ohe Y, Sakamoto H, Tsuta K, Matsuno Y, Tateishi U et al (2005) Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 23(28):6829–6837PubMedCrossRef Takano T, Ohe Y, Sakamoto H, Tsuta K, Matsuno Y, Tateishi U et al (2005) Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 23(28):6829–6837PubMedCrossRef
23.
Zurück zum Zitat Cappuzzo F (2008) EGFR FISH versus mutation: different tests, different end-points. Lung Cancer 60(2):160–165PubMedCrossRef Cappuzzo F (2008) EGFR FISH versus mutation: different tests, different end-points. Lung Cancer 60(2):160–165PubMedCrossRef
24.
Zurück zum Zitat Italiano A, Vandenbos FB, Otto J, Mouroux J, Fontaine D, Marcy PY et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 17(6):981–985PubMedCrossRef Italiano A, Vandenbos FB, Otto J, Mouroux J, Fontaine D, Marcy PY et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 17(6):981–985PubMedCrossRef
25.
Zurück zum Zitat Hirsch FR, Varella-Garcia M, Bunn PA, Di Maria MV, Veve R, Bremmes RM et al (2003) Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 21(20):3798–3807PubMedCrossRef Hirsch FR, Varella-Garcia M, Bunn PA, Di Maria MV, Veve R, Bremmes RM et al (2003) Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 21(20):3798–3807PubMedCrossRef
26.
Zurück zum Zitat Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J et al (2005) Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med 353(2):133–144PubMedCrossRef Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J et al (2005) Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med 353(2):133–144PubMedCrossRef
27.
Zurück zum Zitat Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT et al (2008) Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol 26(9):1472–1478PubMedCrossRef Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT et al (2008) Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol 26(9):1472–1478PubMedCrossRef
28.
Zurück zum Zitat Yatabe Y, Takahashi T, Mitsudomi T (2008) Epidermal growth factor receptor gene amplification is acquired in association with tumor progression of EGFR-mutated lung cancer. Cancer Res 68(7):2106–2111PubMedCrossRef Yatabe Y, Takahashi T, Mitsudomi T (2008) Epidermal growth factor receptor gene amplification is acquired in association with tumor progression of EGFR-mutated lung cancer. Cancer Res 68(7):2106–2111PubMedCrossRef
29.
Zurück zum Zitat Hirsch FR, Scagliotti GV, Langer CJ, Varella-Garcia M, Franklin WA (2003) Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer 41(suppl 1):S29–S42PubMedCrossRef Hirsch FR, Scagliotti GV, Langer CJ, Varella-Garcia M, Franklin WA (2003) Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer 41(suppl 1):S29–S42PubMedCrossRef
30.
Zurück zum Zitat Pirker E, Paz Ares L, Eberhardt W, Krzakowski M, Störkel S, Heeger S et al. (2011) Epidermal growth factor receptor (EGFR) expression as a predictor of survival for first-line chemotherapy plus cetuximab in FLEX study patients with advanced non-small cell lung cancer (NSCLC). Presented at WCLC in Amsterdam. Abstract 01.06.2011 Pirker E, Paz Ares L, Eberhardt W, Krzakowski M, Störkel S, Heeger S et al. (2011) Epidermal growth factor receptor (EGFR) expression as a predictor of survival for first-line chemotherapy plus cetuximab in FLEX study patients with advanced non-small cell lung cancer (NSCLC). Presented at WCLC in Amsterdam. Abstract 01.06.2011
31.
Zurück zum Zitat Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181PubMedCrossRef Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181PubMedCrossRef
32.
Zurück zum Zitat Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S et al (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132PubMedCrossRef Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S et al (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2):123–132PubMedCrossRef
33.
Zurück zum Zitat Liang Z, Zhang J, Zeng X, Gao J, Wu S, Liu T et al. (2010) Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC Cancer 10:376 Liang Z, Zhang J, Zeng X, Gao J, Wu S, Liu T et al. (2010) Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC Cancer 10:376
34.
Zurück zum Zitat Soh J, Okumura N, Lockwood WW, Yamamoto H, Shigematsu H, Zhang W et al (2009) Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells. PloS one 4(10):e7464PubMedCrossRef Soh J, Okumura N, Lockwood WW, Yamamoto H, Shigematsu H, Zhang W et al (2009) Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells. PloS one 4(10):e7464PubMedCrossRef
36.
Zurück zum Zitat Eberhard DA, Giaccone G, Johnson BE, Non-small-cell lung cancer working group (2008) Biomarkers of response to epidermal growth factor receptor inhibitors in non-small-cell lung cancer working group: standardization for use in the clinical trial setting. J Clin Oncol 26(6):983–994PubMedCrossRef Eberhard DA, Giaccone G, Johnson BE, Non-small-cell lung cancer working group (2008) Biomarkers of response to epidermal growth factor receptor inhibitors in non-small-cell lung cancer working group: standardization for use in the clinical trial setting. J Clin Oncol 26(6):983–994PubMedCrossRef
37.
Zurück zum Zitat Tomonaga N, Nakamura Y, Yamaguchi H, Ikeda T, Mizoguchi K, Motoshima K et al. (2011) Analysis of intra-tumor heterogeneity of EGFR mutations in mixed-type lung adenocarcinoma. Poster presented at IASCL 14th world conference on lung cancer, Amsterdam Tomonaga N, Nakamura Y, Yamaguchi H, Ikeda T, Mizoguchi K, Motoshima K et al. (2011) Analysis of intra-tumor heterogeneity of EGFR mutations in mixed-type lung adenocarcinoma. Poster presented at IASCL 14th world conference on lung cancer, Amsterdam
38.
Zurück zum Zitat Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K (2008) Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci 99(5):929–935PubMedCrossRef Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K (2008) Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci 99(5):929–935PubMedCrossRef
39.
Zurück zum Zitat Yatabe Y, Matsuo K, Mitsudomi T (2011) Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol 29(22):2972–2977PubMedCrossRef Yatabe Y, Matsuo K, Mitsudomi T (2011) Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol 29(22):2972–2977PubMedCrossRef
40.
Zurück zum Zitat Chang YL, Wu CT, Shih JY, Lee YC (2011) Comparison of p53 and epidermal growth factor receptor gene status between primary tumors and lymph node metastases in non-small cell lung cancers. Ann Surg Oncol 18(2):543–550 Chang YL, Wu CT, Shih JY, Lee YC (2011) Comparison of p53 and epidermal growth factor receptor gene status between primary tumors and lymph node metastases in non-small cell lung cancers. Ann Surg Oncol 18(2):543–550
41.
Zurück zum Zitat Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS et al (2009) Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol 4(7):809–815PubMedCrossRef Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS et al (2009) Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol 4(7):809–815PubMedCrossRef
42.
Zurück zum Zitat Jänne PA, Borras AM, Kuang Y, Rogers AM, Joshi VA, Liyanage H et al (2006) A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin Cancer Res 12(3 Pt 1):751–758PubMedCrossRef Jänne PA, Borras AM, Kuang Y, Rogers AM, Joshi VA, Liyanage H et al (2006) A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin Cancer Res 12(3 Pt 1):751–758PubMedCrossRef
43.
Zurück zum Zitat Morinaga R, Okamoto I, Fujita Y, Arao T, Sekijima M, Nishio K et al (2008) Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non-small cell lung cancer. Cancer Sci 99(12):2455–2460PubMedCrossRef Morinaga R, Okamoto I, Fujita Y, Arao T, Sekijima M, Nishio K et al (2008) Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non-small cell lung cancer. Cancer Sci 99(12):2455–2460PubMedCrossRef
44.
Zurück zum Zitat Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V et al (2008) Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer 99(6):923–929PubMedCrossRef Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V et al (2008) Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer 99(6):923–929PubMedCrossRef
45.
Zurück zum Zitat Bozzetti C, Tiseo M, Lagrasta C, Nizzoli R, Guazzi A, Graiani G et al (2010) Is cytology reliable for epidermal growth factor receptor gene evaluation in non-small cell lung cancer? J Thorac Oncol 5(4):551–553PubMedCrossRef Bozzetti C, Tiseo M, Lagrasta C, Nizzoli R, Guazzi A, Graiani G et al (2010) Is cytology reliable for epidermal growth factor receptor gene evaluation in non-small cell lung cancer? J Thorac Oncol 5(4):551–553PubMedCrossRef
46.
Zurück zum Zitat Monaco SE, Nikiforova MN, Cieply K, Teot LA, Khalbuss WE, Dacic S et al (2010) A comparison of EGFR and KRAS status in primary lung carcinoma and matched metastases. Hum Pathol 41(1):94–102PubMedCrossRef Monaco SE, Nikiforova MN, Cieply K, Teot LA, Khalbuss WE, Dacic S et al (2010) A comparison of EGFR and KRAS status in primary lung carcinoma and matched metastases. Hum Pathol 41(1):94–102PubMedCrossRef
47.
Zurück zum Zitat Meert AP, Martin B, Verdebout JM, Paesmans M, Berghmans T, Ninane V et al (2004) Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the diagnostic biopsies and the corresponding resected tumors in non-small cell lung cancer. Lung Cancer 44(3):295–301PubMedCrossRef Meert AP, Martin B, Verdebout JM, Paesmans M, Berghmans T, Ninane V et al (2004) Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the diagnostic biopsies and the corresponding resected tumors in non-small cell lung cancer. Lung Cancer 44(3):295–301PubMedCrossRef
48.
Zurück zum Zitat Rao C, Hu Q, Ma J, Li J, Zhang C, Shen L et al. (2010) Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy. J Exp Clin Cancer Res 29:7 Rao C, Hu Q, Ma J, Li J, Zhang C, Shen L et al. (2010) Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy. J Exp Clin Cancer Res 29:7
49.
Zurück zum Zitat Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L et al (2009) Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol 4(10):1212–1220PubMedCrossRef Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L et al (2009) Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol 4(10):1212–1220PubMedCrossRef
50.
Zurück zum Zitat Felip E, Rojo F, Reck M, Heller A, Klughammer B, Sala G et al (2008) A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy. Clin Cancer Res 14(12):3867–3874PubMedCrossRef Felip E, Rojo F, Reck M, Heller A, Klughammer B, Sala G et al (2008) A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy. Clin Cancer Res 14(12):3867–3874PubMedCrossRef
51.
Zurück zum Zitat De Pas T, Pelosi G, de Braud F, Veronesi G, Curigliano G, Leon ME et al (2004) Modulation of epidermal growth factor receptor status by chemotherapy in patients with locally advanced non-small-cell lung cancer is rare. J Clin Oncol 22(24):4966–4970PubMedCrossRef De Pas T, Pelosi G, de Braud F, Veronesi G, Curigliano G, Leon ME et al (2004) Modulation of epidermal growth factor receptor status by chemotherapy in patients with locally advanced non-small-cell lung cancer is rare. J Clin Oncol 22(24):4966–4970PubMedCrossRef
52.
Zurück zum Zitat Clark GM, Zborowski DM, Culbertson JL, Whitehead M, Savoie M, Seymour L et al (2006) Clinical utility of epidermal growth factor receptor expression for selecting patients with advanced non-small cell lung cancer for treatment with erlotinib. J Thorac Oncol 1(8):837–846PubMedCrossRef Clark GM, Zborowski DM, Culbertson JL, Whitehead M, Savoie M, Seymour L et al (2006) Clinical utility of epidermal growth factor receptor expression for selecting patients with advanced non-small cell lung cancer for treatment with erlotinib. J Thorac Oncol 1(8):837–846PubMedCrossRef
53.
Zurück zum Zitat Badalian G, Barbai T, Rásó E, Derecskei K, Szendrôi M, Tímár J et al (2007) Phenotype of bone metastases of non-small cell lung cancer: epidermal growth factor receptor expression and K-RAS mutational status. Pathol Oncol Res 13(2):99–104PubMedCrossRef Badalian G, Barbai T, Rásó E, Derecskei K, Szendrôi M, Tímár J et al (2007) Phenotype of bone metastases of non-small cell lung cancer: epidermal growth factor receptor expression and K-RAS mutational status. Pathol Oncol Res 13(2):99–104PubMedCrossRef
54.
Zurück zum Zitat Fan X, Furnari FB, Cavenee WK, Castresana JS (2001) Non-isotopic silver-stained SSCP is more sensitive than automated direct sequencing for the detection of PTEN mutations in a mixture of DNA extracted from normal and tumor cells. Int J Oncol 18(5):1023–1026PubMed Fan X, Furnari FB, Cavenee WK, Castresana JS (2001) Non-isotopic silver-stained SSCP is more sensitive than automated direct sequencing for the detection of PTEN mutations in a mixture of DNA extracted from normal and tumor cells. Int J Oncol 18(5):1023–1026PubMed
55.
Zurück zum Zitat Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ et al (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 20(4):696–702PubMedCrossRef Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ et al (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 20(4):696–702PubMedCrossRef
56.
Zurück zum Zitat Williams C, Pontén F, Moberg C, Söderkvist P, Uhlén M, Pontén J et al (1999) A high frequency of sequence alterations is due to formalin fixation of archival specimens. Am J Pathol 155(5):1467–1471PubMedCrossRef Williams C, Pontén F, Moberg C, Söderkvist P, Uhlén M, Pontén J et al (1999) A high frequency of sequence alterations is due to formalin fixation of archival specimens. Am J Pathol 155(5):1467–1471PubMedCrossRef
57.
Zurück zum Zitat Nguyen KSH, Kobayashi S, Costa DB (2009) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 10(4):281–289PubMedCrossRef Nguyen KSH, Kobayashi S, Costa DB (2009) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 10(4):281–289PubMedCrossRef
58.
Zurück zum Zitat Kosaka T, Yatabe Y, Endoh H, Yoshida K, Hida T, Tsuboi M et al (2006) Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res 12(19):5764–5769PubMedCrossRef Kosaka T, Yatabe Y, Endoh H, Yoshida K, Hida T, Tsuboi M et al (2006) Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res 12(19):5764–5769PubMedCrossRef
59.
Zurück zum Zitat Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73PubMedCrossRef Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2(3):e73PubMedCrossRef
60.
Zurück zum Zitat Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792PubMedCrossRef Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792PubMedCrossRef
61.
Zurück zum Zitat Matsumoto S, Takahashi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T et al (2006) Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 119(6):1491–1494PubMedCrossRef Matsumoto S, Takahashi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T et al (2006) Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 119(6):1491–1494PubMedCrossRef
62.
Zurück zum Zitat Cortot AB, Italiano A, Burel-Vandenbos F, Martel-Planche G, Hainaut P (2010) KRAS mutation status in primary nonsmall cell lung cancer and matched metastases. Cancer 116(11):2682–2687PubMedCrossRef Cortot AB, Italiano A, Burel-Vandenbos F, Martel-Planche G, Hainaut P (2010) KRAS mutation status in primary nonsmall cell lung cancer and matched metastases. Cancer 116(11):2682–2687PubMedCrossRef
63.
Zurück zum Zitat Bozzetti C, Tiseo M, Lagrasta C, Nizzoli R, Guazzi A, Leonardi F et al (2008) Comparison between epidermal growth factor receptor (EGFR) gene expression in primary non-small cell lung cancer (NSCLC) and in fine-needle aspirates from distant metastatic sites. J Thorac Oncol 3(1):18–22PubMedCrossRef Bozzetti C, Tiseo M, Lagrasta C, Nizzoli R, Guazzi A, Leonardi F et al (2008) Comparison between epidermal growth factor receptor (EGFR) gene expression in primary non-small cell lung cancer (NSCLC) and in fine-needle aspirates from distant metastatic sites. J Thorac Oncol 3(1):18–22PubMedCrossRef
Metadaten
Titel
Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer
verfasst von
Jan Nyrop Jakobsen
Jens Benn Sørensen
Publikationsdatum
01.02.2012
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 2/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1791-9

Weitere Artikel der Ausgabe 2/2012

Cancer Chemotherapy and Pharmacology 2/2012 Zur Ausgabe

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Alter verschlechtert Prognose bei Endometriumkarzinom

11.05.2024 Endometriumkarzinom Nachrichten

Ein höheres Alter bei der Diagnose eines Endometriumkarzinoms ist mit aggressiveren Tumorcharakteristika assoziiert, scheint aber auch unabhängig von bekannten Risikofaktoren die Prognose der Erkrankung zu verschlimmern.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Update Onkologie

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