Publications of Faculty of Medicine:Role of Smad-4 and P-Cadherin Expression in Progression of Colorectal Carcinoma: A Clinicopathological and Immunohistochemical Study: Abstract

Role of Smad-4 and P-Cadherin Expression in Progression of Colorectal Carcinoma: A Clinicopathological and Immunohistochemical Study
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Colorectal carcinoma is the third leading cause of cancerrelated deaths in the United States. Approximately one-half of colorectal carcinoma patients already have metastases at the time of diagnosis. Smad4 is an intracellular transmitter of TGF-fl signals and its tumor suppressor function is presumed to reside in its capacity to mediate TGF-J3-induced growth inhibition. The roles of Smad-4 in colorectal carcinogenesis are complex and comprise tumor promoting functions particularly in late stage carcinogenesis. Importantly. functional inactivation of Smad4 in colon carcinomas frequently occurs at late stages when tumors acquire invasive and metastatic capabilities. Placental (P)-cadherin was first identified in mouse placenta. The intracellular domain of classic cadherins interacts with various catenin proteins such as h- and gcatenin. In addition to their adhesive functions, classic cadherins modulate transduction of signals and activate Rhofamily GTPases. Therefore, alterations among cadherin molecules can affect not only the adhesive properties of a cell but also its signal transduction which can affect many kinds of cell activities, organ development and tumorigenesis. Aim of the Work: The purpose of the current study was to investigate the role of smad-4 and p-cadherin in colorectal adcnocarcinomas as well as to verify whether they can be considered as markers of prognostic significance in patients with colorectal carcinoma. Patients and Methods: Tissue biopsies were taken from paraffin-embedded tissue blocks of 60 cases including 10 normal non-neoplastic mucosae, 50 colorectal carcinomas. Using immunohistochemical technique, antibodies against Pcadherin and smad-4. were applied to stain the tissue biopsies used in this study. Results: Statistically significant inverse correlations were found between P-cadherin and Smad-4 expressions and different clinicopathological variables mainly tumor grade, patient's TNM stage and distant metastasis. Conclusions: In conclusion, we investigated the significance of loss of SMAD4 in colorectal cancer; loss of nuclear and weak cytoplasmic SMAD4 expression is suggestive of being involved in prognosis of colorectal carcinomas and explored the possible underlying mechanisms associated with poor patient's outcome. Our findings suggest that SMAD4 is a critical prognostic factor. Similarly, on the basis of these results, t is possible to suggest P-cadherin as an early marker of poor prognosis. The lack of P-cadherin and Smad-4 expression could constitute a hallmark of aggressive biological behavior in colorectal carcinomas. Key Words: Smad-4 — P-cadherin — Colorectal carcinoma — Clinicopathological — lmmunohisiochemical