Two Subtypes of Mucinous Adenocarcinoma of The Colorectum: Clinicopathological and Genetic Features

Abstract

This work is aimed at comparing mucinous colorectal adenocarcinomas (MUC) and non-mucinous colorectal adenocarcinomas (non-MUC), and at verifying the existence of two different subgroups of MUC, in terms of clinicopathological features, chromosomal alterations, and outcome, in a geographical area where mucinous colorectal cancer resulted as being very frequent. One hundred and fifty-six unselected patients who underwent curative colorectal resection for sporadic colorectal cancer over a 4-year period were evaluated for histological classification as to MUC and non-MUC subtype, for microsatellite instability (MSI) using six microsatellite markers, and for the presence of p27, Fhit, and cyclooxygenase-2 (Cox-2). Molecular data, immunohistochemical results, recurrence frequency, and patient survival were analyzed statistically in relation to histological subtypes. MUC accounted for 38.5% of all colorectal carcinomas. Compared to non-MUCs, MUCs were more frequently located in the proximal colon (p < 0.001), and more frequently showed MSI phenotype (p < 0.001), altered protein expression of hMlh1 (p = 0.030), Fhit (p <0.001), and p27 (p < 0.001). Compared to MUC with microsatellite-stable (MSS) phenotype, MUC with MSI more frequently resulted as being located in the proximal colon (p = 0.013), and more frequently showed altered expression of hMlh1 (p < 0.001), hMsh2 (p = 0.008), Fhit (p < 0.001), and p27 (p = 0.015). Significantly better survival of patients with proximal MUC (p = 0,012), with MSI MUC (p = 0.017), and with MUC with altered p27 expression (p = 0.02). The results of the present study confirm that MUC represents distinct clinicopathological and genetic features as compared to non-mucinous tumors and support the hypothesis that MUC includes two subtypes with different genetic pathways and behavior.