Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?
Kavanagh, Dara O Chambers, Gillian O'Grady, Liam Barry, Kevin M Waldron, Ronan P Bennani, Fadel Eustace, Paul W Tobbia, Iqdam
Kavanagh, Dara O
Chambers, Gillian
O'Grady, Liam
Barry, Kevin M
Waldron, Ronan P
Bennani, Fadel
Eustace, Paul W
Tobbia, Iqdam
Advisors
Editors
Other Contributors
Date
2012-01-31T15:54:58Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adult
Aged
Aged, 80 and over
Cohort Studies
Colorectal Neoplasms/*diagnosis/genetics/*metabolism/pathology
Female
*Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Staging
Prognosis
Receptor, erbB-2/genetics/*metabolism
Aged
Aged, 80 and over
Cohort Studies
Colorectal Neoplasms/*diagnosis/genetics/*metabolism/pathology
Female
*Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Staging
Prognosis
Receptor, erbB-2/genetics/*metabolism
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
BACKGROUND: The development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer. METHODS: Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5. RESULTS: 114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators. CONCLUSION: HER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy.
Language
eng
Citation
ISSN
1471-2407 (Electronic)
1471-2407 (Linking)
1471-2407 (Linking)
eISSN
ISBN
DOI
10.1186/1471-2407-9-1
PMID
19118499