Molecular pathological subclassification of mucinous adenocarcinoma of the colorectum

Abstract

The purpose of the present report was to examine the possibility of molecular pathological subtyping of mucinous adenocarcinomas (MAC) of the colorectum. Thirty-five formalin-fixed and paraffin-embedded MAC specimens of the colorectum were analyzed. Genetic alterations of p53 gene and microsatellite instability (MSI) as well as immunohistochemical analysis of mucin subtypes (human gastric mucin (HGM), anti-mucin monoclonal antibody recognizing gastric gland mucous cells-1, MUC2, CD10) and expression levels of human mutL homolog 1 (hMLH1), p53 and Ki-67 were performed. According to MSI and p53 status, these tumors were subclassified into three groups: mutator-type tumors with a high frequency of MSI (20%), suppressor/p53-type tumors with p53 mutation, p53 overexpression or loss of heterozygosity of D17S250 (an adjacent locus to p53; 40%) and the unclassified tumors (40%). The suppressor/p53-type tumors had a significant association with distal colon location (P = 0.019), venous invasion (P = 0.002), extent of lymph node metastasis (P = 0.007) and higher tumor stage (P = 0.018). In contrast, mutator-type tumors had frequent expression of HGM (P = 0.005) and prominent lymphocytic infiltration at the advancing front of the tumor (P = 0.005). These results indicate that MAC of the colorectum could be subclassified according to molecular pathological background, reflecting distinct clinicopathological and phenotypic characteristics.