Apoptosis and Cell-Cycle Regulatory Proteins in Colorectal Carcinoma: An Immunohistochemical Study, EMAN S. OMAR, MAGDA H. BAKR, NEHAL S. ZAFER, NASHWA M. EMARA and SAMIA A. YOUSSEF
Abstract
Background: Apoptosis or programmed cell death repre-sent a mechanism by which cells possessing DNA damage can be deleted. The Bcl-xl is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations.
Aim: The aim of this study was to investigate the apoptotic index and the Immunohistochemical expression of Bcl-xl as well as FHIT protein in benign and malignant colorectal lesions with correlation to clinicopathological factors.
Materials and Methods: The quantitative assessment of apoptotic index (AI) and Immunoreactivity of bcl-xl and FHIT proteins were examined in 90 Egyptian patients with different types of colorectal lesions using immunohistochemistry, with correlation to clinicopathological factors.
Results: Apoptotic index of all studied cases showed significant correlation in relation to grade of dysplasia, grade, stage, nodal status and distant spread of colorectal carcinoma. No significant correlation to histopathological type, age, gender or overall survival of patients.
As regard to Bcl-xI; the results showed expression in all control cases in the bottom of crypts, while it was reduced in dysplastic lesions but without significant correlation. In malignant lesions it was over expressed in 68.3% with signif-icant correlation to type, grade, stage, distant spread and overall survival, no significant correlation to lymph node status, age or gender of patients.
On the other hand FHIT protein was reduced in dysplasia (47.4%) with more reduction in high grade. In malignant lesions FHIT was reduced in 56.7%, with significant correlation to type and grade of colorectal carcinoma, no significance correlation to other clinicopathological variables. The examined cases revealed increasing mean AI and Bcl-xl expression from dysplastic to neoplastic cases in spite of decreasing FHIT expression but without significant correlation (p value = 0.210).
Conclusion: These data indicate that over expression of Bcl-xI and reduction of FHIT protein as well as AI may be of central significance in differential diagnosis between high
grade dysplasia and malignant lesions of colon and that increased Bcl-xl expression may be a risk factor for disease recurrence and cancer related patient death.