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Background: Metastasis is a major cause of death in colorectal carcinoma (CRC). Epithelial to mesenchymal transition (EMT) plays a role in promoting carcinoma invasion and metastasis. Many molecules are crucial in EMT, including claudin-1 and S100A4. Aim of work: The aim of this study is to assess the pattern of expression and the prognostic significance of claudin-1 and S100A4 in primary colorectal carcinoma. Methods: Claudin-1 and S100A4 expressions were retrospectively analysed by immunohistochemistry in 55 paraffin-embedded specimens of patients with primary colorectal carcinoma. The expressions were correlated with clinicopathological variables, Dukes staging and lymph node metastasis. Results: Normal colonic and rectal mucosa exhibited diffuse, strong circumferential linear membranous pattern of claudin-1 staining (score 0). Twenty six cases (65%) of primary colorectal carcinomas showed decreased claudin1 expression compared to normal mucosa and 14 cases (35%) showed similar claudin1 expression (score 0). None of the studied cases showed increased claudin1 expression. A highly statistically significant relationship was found between claudin1 expression and Lymphovascular invasion (p=0.003), degree of lymphocytic infiltration, peritumoral budding, lymph node ratio, lymph node metastasis and Dukes staging (p<0.001). Fourteen cases (35%) showed negative S100A4 expression (score 0-2), 10 cases (25%) showed mild positive S100A4 expression (score 3), 9 cases (22.5%) showed moderate positive S100A4 expression (score 4-5) and 7 cases (17.5%) showed marked positive S100A4 expression (score 6). A highly statistically significant relationship was found between S100A4 expression and grade of differentiation, lymphovascular invasion (p=0.002), lymphocytic infiltration, peritumoral budding, lymph node metastasis, lymph node ratio and Dukes staging (p<0.001). By Pearson's correlation coefficient (r) method, there is a strong inverse correlation between claudin1 and S100A4 expression. Conclusions: Loss of tight junctions represented by decreased claudin1 expression and acquisition of mesenchymal properties represented by S100A4 overexpression are important in primary colorectal carcinoma progression and metastasis.

THE SIGNIFICANCE OF CLAUDIN-1 AND S100A4 EXPRESSION IN PRIMARY COLORECTAL CARCINOMA