Skip to main content
Top
Published in: Virchows Archiv 3/2006

Open Access 01-09-2006 | Original Article

Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray

Authors: Frédéric Bibeau, Florence Boissière-Michot, Jean-Christophe Sabourin, Sophie Gourgou-Bourgade, Michèle Radal, Frédérique Penault-Llorca, Philippe Rochaix, Laurent Arnould, Marie-Pierre Bralet, David Azria, Marc Ychou

Published in: Virchows Archiv | Issue 3/2006

Login to get access

Abstract

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique.
Literature
1.
go back to reference Atkins D, Reiffen KA, Tegtmeier CL, Winther H, Bonato MS, Storkel S (2004) Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 52:893–901PubMedCrossRef Atkins D, Reiffen KA, Tegtmeier CL, Winther H, Bonato MS, Storkel S (2004) Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 52:893–901PubMedCrossRef
2.
go back to reference Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803–1810PubMedCrossRef Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803–1810PubMedCrossRef
3.
go back to reference Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van CE (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345PubMedCrossRef Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van CE (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345PubMedCrossRef
4.
go back to reference Cunningham MP, Essapen S, Thomas H, Green M, Lovell DP, Topham C, Marks C, Modjtahedi H (2005) Coexpression, prognostic significance and predictive value of EGFR, EGFRvIII and phosphorylated EGFR in colorectal cancer. Int J Oncol 27:317–325PubMed Cunningham MP, Essapen S, Thomas H, Green M, Lovell DP, Topham C, Marks C, Modjtahedi H (2005) Coexpression, prognostic significance and predictive value of EGFR, EGFRvIII and phosphorylated EGFR in colorectal cancer. Int J Oncol 27:317–325PubMed
5.
go back to reference Dei Tos AP, Ellis I (2005) Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods? Eur J Cancer 41:1383–1392PubMedCrossRef Dei Tos AP, Ellis I (2005) Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods? Eur J Cancer 41:1383–1392PubMedCrossRef
6.
go back to reference Goldstein NS, Armin M (2001) Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 92:1331–1346PubMedCrossRef Goldstein NS, Armin M (2001) Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 92:1331–1346PubMedCrossRef
7.
go back to reference Gomaa W, Ke Y, Fujii H, Helliwell T (2005) Tissue microarray of head and neck squamous carcinoma: validation of the methodology for the study of cutaneous fatty acid-binding protein, vascular endothelial growth factor, involucrin and Ki-67. Virchows Arch 447:701–709PubMedCrossRef Gomaa W, Ke Y, Fujii H, Helliwell T (2005) Tissue microarray of head and neck squamous carcinoma: validation of the methodology for the study of cutaneous fatty acid-binding protein, vascular endothelial growth factor, involucrin and Ki-67. Virchows Arch 447:701–709PubMedCrossRef
8.
go back to reference Gupta M, Varma V, Costonis G, Lawson D, Cohen C (2005) Epidermal Growth Factor Receptor (EGFR) in primary and metastatic colorectal carcinoma. Mod Pathol 18(Suppl 1):105A Gupta M, Varma V, Costonis G, Lawson D, Cohen C (2005) Epidermal Growth Factor Receptor (EGFR) in primary and metastatic colorectal carcinoma. Mod Pathol 18(Suppl 1):105A
9.
go back to reference Hernandez BY, Frierson HF, Moskaluk CA, Li YJ, Clegg L, Cote TR, McCusker ME, Hankey BF, Edwards BK, Goodman MT (2005) CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray. Hum Pathol 36:275–281PubMedCrossRef Hernandez BY, Frierson HF, Moskaluk CA, Li YJ, Clegg L, Cote TR, McCusker ME, Hankey BF, Edwards BK, Goodman MT (2005) CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray. Hum Pathol 36:275–281PubMedCrossRef
10.
go back to reference Holbro T, Civenni G, Hynes NE (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284:99–110PubMedCrossRef Holbro T, Civenni G, Hynes NE (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284:99–110PubMedCrossRef
11.
go back to reference Italiano A, Saint-Paul MC, Caroli-Bosc FX, Francois E, Bourgeon A, Benchimol D, Gugenheim J, Michiels JF (2005) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. Ann Oncol 16:1503–1507PubMedCrossRef Italiano A, Saint-Paul MC, Caroli-Bosc FX, Francois E, Bourgeon A, Benchimol D, Gugenheim J, Michiels JF (2005) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. Ann Oncol 16:1503–1507PubMedCrossRef
12.
go back to reference Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S, Duval A, Hamelin R, Flejou JF (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch 443:115–121PubMedCrossRef Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S, Duval A, Hamelin R, Flejou JF (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch 443:115–121PubMedCrossRef
13.
go back to reference Khalifa MA, Rowsell CH, Gladdy RA, Ko YJ, Hanna S, Smith A, Law C (2006) Expression of epidermal growth factor receptor in primary colorectal adenocarcinoma predicts expression in recurrent disease. Am J Clin Pathol 125:229–233PubMedCrossRef Khalifa MA, Rowsell CH, Gladdy RA, Ko YJ, Hanna S, Smith A, Law C (2006) Expression of epidermal growth factor receptor in primary colorectal adenocarcinoma predicts expression in recurrent disease. Am J Clin Pathol 125:229–233PubMedCrossRef
14.
go back to reference Lax I, Bellot F, Howk R, Ullrich A, Givol D, Schlessinger J (1989) Functional analysis of the ligand binding site of EGF-receptor utilizing chimeric chicken/human receptor molecules. EMBO J 8:421–427PubMed Lax I, Bellot F, Howk R, Ullrich A, Givol D, Schlessinger J (1989) Functional analysis of the ligand binding site of EGF-receptor utilizing chimeric chicken/human receptor molecules. EMBO J 8:421–427PubMed
15.
go back to reference Lockhart C, Berlin JD (2005) The epidermal growth factor receptor as a target for colorectal cancer therapy. Semin Oncol 32:52–60PubMedCrossRef Lockhart C, Berlin JD (2005) The epidermal growth factor receptor as a target for colorectal cancer therapy. Semin Oncol 32:52–60PubMedCrossRef
16.
go back to reference Mattoon DR, Lamothe B, Lax I, Schlessinger J (2004) The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. BMC Biol 2:24PubMedCrossRef Mattoon DR, Lamothe B, Lax I, Schlessinger J (2004) The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. BMC Biol 2:24PubMedCrossRef
17.
go back to reference Mobasheri A, Airley R, Foster CS, Schulze-Tanzil G, Shakibaei M (2004) Post-genomic applications of tissue microarrays: basic research, prognostic oncology, clinical genomics and drug discovery. Histol Histopathol 19:325–335PubMed Mobasheri A, Airley R, Foster CS, Schulze-Tanzil G, Shakibaei M (2004) Post-genomic applications of tissue microarrays: basic research, prognostic oncology, clinical genomics and drug discovery. Histol Histopathol 19:325–335PubMed
18.
go back to reference Park KJ, Choi HJ, Roh MS, Kwon HC, Kim C (2005) Intensity of tumor budding and its prognostic implications in invasive colon carcinoma. Dis Colon Rectum 48:1597–1602PubMedCrossRef Park KJ, Choi HJ, Roh MS, Kwon HC, Kim C (2005) Intensity of tumor budding and its prognostic implications in invasive colon carcinoma. Dis Colon Rectum 48:1597–1602PubMedCrossRef
19.
go back to reference Parker C, Roseman BJ, Bucana CD, Tsan R, Radinsky R (1998) Preferential activation of the epidermal growth factor receptor in human colon carcinoma liver metastases in nude mice. J Histochem Cytochem 46:595–602PubMed Parker C, Roseman BJ, Bucana CD, Tsan R, Radinsky R (1998) Preferential activation of the epidermal growth factor receptor in human colon carcinoma liver metastases in nude mice. J Histochem Cytochem 46:595–602PubMed
20.
go back to reference Prall F, Ostwald C, Nizze H, Barten M (2004) Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis. Appl Immunohistochem Mol Morphol 12:111–121PubMed Prall F, Ostwald C, Nizze H, Barten M (2004) Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis. Appl Immunohistochem Mol Morphol 12:111–121PubMed
21.
go back to reference Prall F, Nizze H, Barten M (2005) Tumour budding as prognostic factor in stage I/II colorectal carcinoma. Histopathology 47:17–24PubMedCrossRef Prall F, Nizze H, Barten M (2005) Tumour budding as prognostic factor in stage I/II colorectal carcinoma. Histopathology 47:17–24PubMedCrossRef
22.
go back to reference Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD, Fidler IJ (1995) Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res 1:19–31PubMed Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD, Fidler IJ (1995) Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res 1:19–31PubMed
23.
go back to reference Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208PubMedCrossRef Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208PubMedCrossRef
24.
go back to reference Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S (2004) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol 22:4772–4778PubMedCrossRef Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S (2004) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol 22:4772–4778PubMedCrossRef
25.
go back to reference Shia J, Klimstra DS, Li AR, Qin J, Saltz L, Teruya-Feldstein J, Akram M, Chung KY, Yao D, Paty PB, Gerald W, Chen B (2005) Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Mod Pathol 18:1350–1356PubMedCrossRef Shia J, Klimstra DS, Li AR, Qin J, Saltz L, Teruya-Feldstein J, Akram M, Chung KY, Yao D, Paty PB, Gerald W, Chen B (2005) Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Mod Pathol 18:1350–1356PubMedCrossRef
26.
go back to reference Simon R, Mirlacher M, Sauter G (2004) Tissue microarrays. Biotechniques 36:98–105PubMed Simon R, Mirlacher M, Sauter G (2004) Tissue microarrays. Biotechniques 36:98–105PubMed
27.
go back to reference Singh RK, Tsan R, Radinsky R (1997) Influence of the host microenvironment on the clonal selection of human colon carcinoma cells during primary tumor growth and metastasis. Clin Exp Metastasis 15:140–150PubMedCrossRef Singh RK, Tsan R, Radinsky R (1997) Influence of the host microenvironment on the clonal selection of human colon carcinoma cells during primary tumor growth and metastasis. Clin Exp Metastasis 15:140–150PubMedCrossRef
28.
go back to reference Sobin LH, Wittekind CH (eds) (2002) TNM classification of malignant tumours, 6th edn. Wiley-Liss, New York Sobin LH, Wittekind CH (eds) (2002) TNM classification of malignant tumours, 6th edn. Wiley-Liss, New York
29.
go back to reference Spano JP, Fagard R, Soria JC, Rixe O, Khayat D, Milano G (2005) Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives. Ann Oncol 16:189–194PubMedCrossRef Spano JP, Fagard R, Soria JC, Rixe O, Khayat D, Milano G (2005) Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives. Ann Oncol 16:189–194PubMedCrossRef
30.
go back to reference Ueno H, Murphy J, Jass JR, Mochizuki H, Talbot IC (2002) Tumour ‘budding’ as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology 40:127–132PubMedCrossRef Ueno H, Murphy J, Jass JR, Mochizuki H, Talbot IC (2002) Tumour ‘budding’ as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology 40:127–132PubMedCrossRef
Metadata
Title
Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray
Authors
Frédéric Bibeau
Florence Boissière-Michot
Jean-Christophe Sabourin
Sophie Gourgou-Bourgade
Michèle Radal
Frédérique Penault-Llorca
Philippe Rochaix
Laurent Arnould
Marie-Pierre Bralet
David Azria
Marc Ychou
Publication date
01-09-2006
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 3/2006
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-006-0247-9

Other articles of this Issue 3/2006

Virchows Archiv 3/2006 Go to the issue