Clinico-Pathological and Prognostic Significance of p53, Bcl-2 and Her-2/neu Protein Markers in Colorectal Cancer Using Tissue Microarray.

Background: The prognostic role of her-2/neu has been established in breast cancer but remains controversial in colorectal cancer (CRC). Widespread genetic mutations in colorectal carcinogenesis exist on chromosome 17. Her- 2/neu gene and the tumor suppressor gene p53 are both located on this chromosome. Bcl-2 protein prolongs survival of a variety of cells by blocking apoptosis. The aim of this study is to evaluate the relationship between the overexpression of p53, bcl-2 and her-2/neu protein markers and the clinico-pathologic characteristics of CRC, and their influence on survival rates.

Patients And Methods: One hundred and four cases of CRC had paraffin blocks with representative tissue, and sufficient follow-up data. They were arrayed and evaluated for protein marker expression using tissue microarray (TMA).

Results: Ten (9.6%), 35 (33.7%) and 27 (26%) of the patients were her-2/neu, p53 and bcl-2 positive, respectively. None of the examined clinico-pathologic factors had a significant relation with her-2/neu overexpression. Patients with +ve bcl-2 had a significantly higher mean age (52.4-/+13.3years) compared to 45.4-/+14.4 years for bcl-2 negative patients, p=0.03. Positive p53 was overexpressed in 20/44 (45.5%), 6/17 (35%), 9/43 (21%) cases of the colon, recto-sigmoid, and rectal sites, respectively, p=0.05. For the whole population, p53 overexpression had a significantly lower disease-free survival (DFS). For patients with Dukes' stage B, overexpression of p53 protein had a significant reduced overall survival (OS) p=0.04, metastasis free survival (MFS) p=0.004, and DFS p=0.01 rates. Expression of bcl-2 had a significantly better MFS p=0.001, while her-2/neu overexpression worsened the OS rate significantly, p=0.04.

Conclusion: This study recommends the application of TMA technique for its economic importance and reliable quick throughput. The results from this study also suggest that overexpression of p53, bcl-2, and her-2/neu protein markers appear to be useful in selecting a group of CRC patients with a worse prognosis and constitute potential candidates for adjuvant therapy. Key Words: Her-2/neu , p53 , Bcl-2 , Colorectal cancer , Tissue microarray , Prognostic factors.