The Significance of Claudin-1 and S100a4 Expression in Primary Colorectal Carcinoma

Abstract

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.

Low Claudin-1 Expression Has Association with Deep Invading and Higher-Grade Colorectal Adenocarcinoma

“…By immunohistochemistry staining of claudin-1 protein, the loss of differentiation ability is characterized by the low claudin-1 expression on high grade or poorly differentiated tumor cells ( Figure E-F). This study result shows there is a significant difference in h-score claudin-1 expression between low-and high-grade adenocarcinoma [8,10,17]. In addition, decreased claudin-1 expression is also related to lymph node metastasis and aggressive behavior [3,9].…”

“…Claudin-1 expression in colorectal cancer has been studied. Kaf et al [8] showed that claudin-1 expression was found to be significantly related to histological grade, morphology subtype, tumor invasion depth, and distant metastasis. This finding is in line with those of Ersoz et al [3] and Suren et al [9] On the contrary, Yoshida et al [10] and Hirakawa et al [11] found that there was no significant relationship of claudin-1 expression in higher grade tumor and tumor invasion depth.…”