Skip to main content
Top
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

HER 2/neu protein expression in colorectal cancer

Authors: B Schuell, T Gruenberger, W Scheithauer, Ch Zielinski, F Wrba

Published in: BMC Cancer | Issue 1/2006

Login to get access

Abstract

Background

Conflicting data exist about the prevalence of HER-2/neu overexpression in colorectal cancer ranging from 0 to 83 %. In our study we tried to clarify the extent of expression and its relationship to clinicopathological parameters.

Methods

This study involved 77 specimens of malignant colorectal cancer lesions of surgically resected patients. HER-2/neu immunohistochemistry was performed using the Hercep-Test Kit.

Results

Out of 77 specimens, 56 were Her-2/neu negative (70%), 20 (26%) showed a barely immunostaining (1+), only 1 (1%) was moderately (2+) and 2 (3%) were strongly positive (3+). Her-2/neu staining (moderately and strongly positive) was only detected in primary tumours of patients with confirmed metastases. No relationship was found between membranous HER-2 expression and patients' gender or differentiation. The median survival time of patients with positive HER-2/neu immunostaining was 21 versus 39 months in patients without HER-2/neu expression (p = 0.088).

Conclusion

The c-erbB protein expression was observed in colorectal cancer but rarely in the therapeutic range (2+ and 3+). There was no significant association with tumour grade, gender, localization of the primary tumour or survival. These data indicate that c-erbB-2 is unlikely to play a major role in the therapeutic management of colorectal cancer.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Saltz LB, Meropol NJ, Loehrer PJ, Needle MN, Kopit J, Mayer RJ: Phase II Trial of cetuximab in patients with refractory colorectal cancer that express the epidermal growth factor receptor. J Clin Oncol. 2004, 22: 1201-1208. 10.1200/JCO.2004.10.182.CrossRefPubMed Saltz LB, Meropol NJ, Loehrer PJ, Needle MN, Kopit J, Mayer RJ: Phase II Trial of cetuximab in patients with refractory colorectal cancer that express the epidermal growth factor receptor. J Clin Oncol. 2004, 22: 1201-1208. 10.1200/JCO.2004.10.182.CrossRefPubMed
3.
go back to reference Schlessinger J: Cell signaling by receptor tyrosine kinase. Cell. 2000, 103: 211-25. 10.1016/S0092-8674(00)00114-8.CrossRefPubMed Schlessinger J: Cell signaling by receptor tyrosine kinase. Cell. 2000, 103: 211-25. 10.1016/S0092-8674(00)00114-8.CrossRefPubMed
4.
go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of HER-2/neu oncogenes. Science. 1987, 234: 177-182.CrossRef Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of HER-2/neu oncogenes. Science. 1987, 234: 177-182.CrossRef
5.
go back to reference Saranath D, Panchal RG, Nair R, Metha AR, Sanghavi VD, Deo MG: Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer. Eur J Cancer. 1992, 28B: 139-143.CrossRef Saranath D, Panchal RG, Nair R, Metha AR, Sanghavi VD, Deo MG: Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer. Eur J Cancer. 1992, 28B: 139-143.CrossRef
6.
go back to reference Rusch V, Baselga J, Cordon-Carlo , Orazem J, Zaman M, Hoda S, McIntosh J, Kurie J, Dmitrovsky E: Differential expression of the epidermal growth factor receptor and its ligand in primary non-small cell lung cancers and adjusent benign lung. Cancer Res. 1993, 53: 2379-2385.PubMed Rusch V, Baselga J, Cordon-Carlo , Orazem J, Zaman M, Hoda S, McIntosh J, Kurie J, Dmitrovsky E: Differential expression of the epidermal growth factor receptor and its ligand in primary non-small cell lung cancers and adjusent benign lung. Cancer Res. 1993, 53: 2379-2385.PubMed
7.
go back to reference Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SA, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989, 244: 707-712.CrossRefPubMed Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SA, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989, 244: 707-712.CrossRefPubMed
8.
go back to reference Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Realmond C, Schlessinger J, Lippman ME, King CR: Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein in primary breast cancer. J Clin Oncol. 1990, 8: 103-112.PubMed Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Realmond C, Schlessinger J, Lippman ME, King CR: Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein in primary breast cancer. J Clin Oncol. 1990, 8: 103-112.PubMed
9.
go back to reference 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: Use of chemotherapy plus monoclonal antibody against HER2 for metastatic breast cancer that overexpress HER2. N Engl J Med. 2001, 344: 783-92. 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: Use of chemotherapy plus monoclonal antibody against HER2 for metastatic breast cancer that overexpress HER2. N Engl J Med. 2001, 344: 783-92. 10.1056/NEJM200103153441101.CrossRefPubMed
10.
go back to reference Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Salamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ et, Press M: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2000, 20: 719-26. 10.1200/JCO.20.3.719.CrossRef Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Salamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ et, Press M: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2000, 20: 719-26. 10.1200/JCO.20.3.719.CrossRef
11.
go back to reference Mann M, Sheng H, Shao J, Williams CS, Pisacane PI, Sliwkowski MX, DuBois RN: Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology. 2001, 120: 1713-9. 10.1053/gast.2001.24844.CrossRefPubMed Mann M, Sheng H, Shao J, Williams CS, Pisacane PI, Sliwkowski MX, DuBois RN: Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology. 2001, 120: 1713-9. 10.1053/gast.2001.24844.CrossRefPubMed
12.
go back to reference Ross JS, McKenna BJ: The Her-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001, 19: 554-68. 10.1081/CNV-100103852.CrossRefPubMed Ross JS, McKenna BJ: The Her-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001, 19: 554-68. 10.1081/CNV-100103852.CrossRefPubMed
13.
go back to reference Caruso ML, Valentini AM: Immunhistochemical p53 overexpression correlated to c-erbB-2 and cathepsin D proteins in colorectal cancer. Anticancer Res. 1996, 16: 3813-8.PubMed Caruso ML, Valentini AM: Immunhistochemical p53 overexpression correlated to c-erbB-2 and cathepsin D proteins in colorectal cancer. Anticancer Res. 1996, 16: 3813-8.PubMed
14.
go back to reference Osako T, Miyahara M, Uchino , Inomata M, Kitano S, Kobayashi M: Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the correlation with patients survival. Oncology. 1998, 55: 548-55. 10.1159/000011911.CrossRefPubMed Osako T, Miyahara M, Uchino , Inomata M, Kitano S, Kobayashi M: Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the correlation with patients survival. Oncology. 1998, 55: 548-55. 10.1159/000011911.CrossRefPubMed
15.
go back to reference Kapitanovic S, Radosevic S, Kapitanovic M, Andelinovic S, Ferencic Z, Tavassoli M, Primorac D, Sonicki Z, Spaventi S, Pavelic K, Spaventi R: The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology. 1997, 112: 1103-13. 10.1016/S0016-5085(97)70120-3.CrossRefPubMed Kapitanovic S, Radosevic S, Kapitanovic M, Andelinovic S, Ferencic Z, Tavassoli M, Primorac D, Sonicki Z, Spaventi S, Pavelic K, Spaventi R: The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology. 1997, 112: 1103-13. 10.1016/S0016-5085(97)70120-3.CrossRefPubMed
16.
go back to reference McKay JA, Loane JF, Ross VG, Ameyaw MM, Murray GI, Cassidy J, McLeod HL: C-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002, 86: 568-573. 10.1038/sj.bjc.6600127.CrossRefPubMedPubMedCentral McKay JA, Loane JF, Ross VG, Ameyaw MM, Murray GI, Cassidy J, McLeod HL: C-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002, 86: 568-573. 10.1038/sj.bjc.6600127.CrossRefPubMedPubMedCentral
19.
go back to reference Kirschbaum MH, Yarden Y: The ErbB/Her family of receptor tyrosine kinase a potential target for chemoprevention of epithelial neoplasm. J Cell Biochem Suppl. 2000, 34: 52-60. 10.1002/(SICI)1097-4644(2000)77:34+<52::AID-JCB10>3.0.CO;2-X.CrossRefPubMed Kirschbaum MH, Yarden Y: The ErbB/Her family of receptor tyrosine kinase a potential target for chemoprevention of epithelial neoplasm. J Cell Biochem Suppl. 2000, 34: 52-60. 10.1002/(SICI)1097-4644(2000)77:34+<52::AID-JCB10>3.0.CO;2-X.CrossRefPubMed
20.
go back to reference Baselga J, Mendelsohn J: The epidermal growth factor receptor as a target for therapy in breast carcinoma. Breast Cancer Res Treat. 1994, 29: 127-138. 10.1007/BF00666188.CrossRefPubMed Baselga J, Mendelsohn J: The epidermal growth factor receptor as a target for therapy in breast carcinoma. Breast Cancer Res Treat. 1994, 29: 127-138. 10.1007/BF00666188.CrossRefPubMed
21.
go back to reference Baselga J, Mendelsohn J: Receptor blockade with monoclonal antibodies as anti-cancer therapy. Pharmacol Ther. 1994, 64: 127-54. 10.1016/0163-7258(94)90036-1.CrossRefPubMed Baselga J, Mendelsohn J: Receptor blockade with monoclonal antibodies as anti-cancer therapy. Pharmacol Ther. 1994, 64: 127-54. 10.1016/0163-7258(94)90036-1.CrossRefPubMed
22.
go back to reference Nathason DR, Culliford AT, Shia J, Chen B, D'Alessio MD, Zeng Z, Nash G, Gerald W, Barany F, Paty P: HER-2/neu expression and gene amplification in colon cancer. Int J Cancer. 2003, 105: 796-802. 10.1002/ijc.11137.CrossRef Nathason DR, Culliford AT, Shia J, Chen B, D'Alessio MD, Zeng Z, Nash G, Gerald W, Barany F, Paty P: HER-2/neu expression and gene amplification in colon cancer. Int J Cancer. 2003, 105: 796-802. 10.1002/ijc.11137.CrossRef
23.
go back to reference Half E, Broaddus R, Danenberg KD, Danenberg PV, Ayers GD, Sinicrope FA: HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer. 2004, 108: 540-548. 10.1002/ijc.11599.CrossRefPubMed Half E, Broaddus R, Danenberg KD, Danenberg PV, Ayers GD, Sinicrope FA: HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer. 2004, 108: 540-548. 10.1002/ijc.11599.CrossRefPubMed
24.
go back to reference Lazaris AC, Theodoroporlos GE, Anastassopulos , Nakopoulou L, Panoussopoulus D, Papadimitriou K: Prognostic significance of p53 and c-erbB-2 immunohistochemical evaluation in colorectal adenocarcinoma. Histol Histopathol. 1995, 10: 661-8.PubMed Lazaris AC, Theodoroporlos GE, Anastassopulos , Nakopoulou L, Panoussopoulus D, Papadimitriou K: Prognostic significance of p53 and c-erbB-2 immunohistochemical evaluation in colorectal adenocarcinoma. Histol Histopathol. 1995, 10: 661-8.PubMed
25.
go back to reference Saeki T, Salomon DS, Johnson GR, Gullick WJ, Mandai K, Yamagami K, Moriwaki S, Tanada M, Takashima S, Tahara E: Association of epidermal growth factor-related peptides and type I receptor tyrosine receptors with prognosis of human colorectal carcinomas. Jpn J Clin Oncol. 1995, 25: 240-9.PubMed Saeki T, Salomon DS, Johnson GR, Gullick WJ, Mandai K, Yamagami K, Moriwaki S, Tanada M, Takashima S, Tahara E: Association of epidermal growth factor-related peptides and type I receptor tyrosine receptors with prognosis of human colorectal carcinomas. Jpn J Clin Oncol. 1995, 25: 240-9.PubMed
26.
go back to reference Ramanathan RK, Hwang JJ, Zamboni WC, Sinicrope FA, Safran H, Wong MK, Earle M, Brufsky A, Evans T, Troetschel M, Ealko C, Day R, Chen HX, Finkelstein S: Low expression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II trail. Cancer Invest. 2004, 22 (6): 858-65. 10.1081/CNV-200039645.CrossRefPubMed Ramanathan RK, Hwang JJ, Zamboni WC, Sinicrope FA, Safran H, Wong MK, Earle M, Brufsky A, Evans T, Troetschel M, Ealko C, Day R, Chen HX, Finkelstein S: Low expression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II trail. Cancer Invest. 2004, 22 (6): 858-65. 10.1081/CNV-200039645.CrossRefPubMed
Metadata
Title
HER 2/neu protein expression in colorectal cancer
Authors
B Schuell
T Gruenberger
W Scheithauer
Ch Zielinski
F Wrba
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-123

Other articles of this Issue 1/2006

BMC Cancer 1/2006 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine