Mucin 1, Thomsen-Friedenreich Expression and Galectin-1 Binding in Endometrioid Adenocarcinoma: An Immunohistochemical Analysis

Abstract

Background and Aim: Altered mucin 1 (MUC1) secretion patterns have been implicated in several cancerous conditions including gastric, colorectal and breast carcinomas. Additionally, an association between the expression of MUC1, Thomsen-Friedenreich (TF) antigen, and binding of gal-1 (gal-1) has been proposed. Therefore, the aims of this study were to determine the frequency and tissue distribution of MUC1, TF and gal-1 binding in endometrioid adenocarcinomas. Materials and Methods: Endometrial carcinomas diagnosed with only one histological tumor form (endometrioid adenocarcinomas) were obtained from 70 patients and classified according to the WHO grading system (G1=50; G2=12; G3=8). An immuno-histochemical analysis was performed with specific antibodies against MUC1 and TF and in addition with biotinylated gal-1, followed by a semiquantitative evaluation and statistical analysis (χ² test and Spearman's correlation coefficient). Results: MUC1, TF and gal-1 were observed in human endometrioid adenocarcinomas. The MUC1 and gal-1 immunoreaction increased from G1 to G3, while TF demonstrated a lower intensity in G3 compared to G1, although with no statistical significance. However TF showed a significant correlation with MUC1 (p=0.019) in G1 and G2 endometrioid adeno-carcinomas, with no observed correlation in G3 tumors. MUC1 and TF demonstrated a significant (p=0.006 and p=0.046, respectively) down-regulation in surgically staged FIGO III/IV compared to FIGO I/II. Gal-1 binding was up-regulated in FIGO III/IV although with no statistical significance. Interestingly, there was an association between gal-1 binding and lymphangiosis (p=0.008). Conclusion: An immuno-histochemical expression of MUC1 and TF and gal-1 binding was demonstrated in human endometrioid adenocarcinomas. Although no significant expression patterns could be demonstrated within different nuclear grading, TF and MUC1 showed a significant correlation in G1/G2 tumors. Therefore, MUC1 and TF might be associated with endometrial malignant transformation. Additionally, MUC1 and TF were down-regulated in stage III/IV tumors, while a higher binding of gal-1 was observed in stage III/IV tumors, suggesting a substantial role of this antigen in endometrial carcinogenesis. Gal-1 binding was associated with lymphangiosis, which is thought to be a poor prognostic marker in endometrial adenocarcinomas. Therefore, MUC1, TF and galectin might have important roles in endometrial pathogenesis and malignant transformation. However, their utilization as specific tumor markers remains unclear and further studies are warranted.