Is mucinous carcinoma of the colorectum a distinct genetic entity?

Abstract

Summary Mucinous carcinomas are defined on the basis of the amount of the mucus component in the tumour mass. Apart from this quantitative criterion, a number of clinicopathological parameters (such as localisation, prevalence in different countries and age groups, association with HNPCC and inflammatory processes) and genetic alterations (e.g. frequency of mutation in Ki-ras and p53 genes, level of MUC2 expression) differentiate these tumours from the non-mucinous ones. Since a different set of genetic lesions implies different inducing agents, these observations suggest that there may be a 'mucinous pathway of carcinogenesis'. Further identification of genetic changes characteristic of the mucinous phenotype will help to understand the aetiology of these tumours and possibly establish markers for detection of the high-risk group.Keywords: mucinous carcinoma; p53; MUC2; aetiology The designation mucinous carcinomas is applied to colorectal tumours in which mucus secretion largely contributes to the tumour growth. Different authors classified colonic tumours as mucinous when the mucin lakes represented 50% (Pihl et al., 1980) to 80% (Umpleby et al., 1985) of the tissue; the definition set by World Health Organization and applied in the more recent reports and in the present minireview requires the mucinous component to represent more than 50% of the tumour (Jass and Sobin, 1990).Whether the mucinous phenotype is associated with relatively poor prognosis is a matter of controversy; more recent multivariate analyses of the course of the disease in a large number of patients indicate that the mucinous carcinomas of the colorectum do not differ in their clinical behaviour from non-mucinous (Sasaki et al., 1987;Halvorsen and Seim, 1988; Hermanek et al., 1989) or signet ring cell carcinomas (Sasaki et al., 1987). The pattern of the genetic lesions in mucinous carcinomas is, however, different from that in non-mucinous ones. Some of these differences are obviously related to the mucinous phenotype (like the level of MUC2 expression) and may be epiphenomenal, while others (such as activation of proto-oncogenes and inactivation of suppressor genes) belong to the group of lesions assumed to be fundamental in carcinogenesis. The present analysis of the recently defined genetic differences as well as indicators of inherent genetic differences between the mucinous and nonmucinous phenotype suggests that distinct molecular lesions occur during the development of these two types of colorectal carcinoma. Clinicopathological parametersSimilar prevalence in the left and the right colon Several studies indicate that 19-40% of non-mucinous sporadic carcinomas are located in the right colon while the majority is found in the left colon (Symonds and Vickery, 1976;Umpleby et al., 1985;Milne, 1994). By contrast, the prevalence of mucinous carcinomas is approximately equal in both segments (Symonds and Vickery, 1976; Sundblad and Paz, 1982;Umpleby et al., 1985). For example, in a recent study of 80 mucinous carcinomas 46% were loca...

MUC2 gene promoter methylation in mucinous and non-mucinous colorectal cancer tissues

“…MSI (5,6), CIMP (5,7) and BRAF (5,8,9) mutation is more frequently in mucinous CRC than in non-mucinous CRC. On the contrary, mutation of APC, KRAS and p53 occurred less in mucinous CRC than in non-mucinous CRC (3,5,10). Therefore, these data indicated that mucinous CRC may have different pathways of pathogenesis from non-mucinous CRC.…”

Mucinous Adenocarcinomas with Intra-Abdominal Dissemination: A Review of Current Therapy

“…Mucinous adenocarcinomas are characterized by a low occurrence of p53 alterations, a high frequency of MSI (MSI-H), a high frequency of KRAS mutations, and a higher apoptotic index than in corresponding nonmucinous tumors [34]. Based on these genetic differences and the more aggressive behavior, some authors have suggested that an alternate mucinous phenotype-related pathway of carcinogenesis might exist and that MCA should be categorized and treated as a biological entity distinct from other colorectal adenocarcinomas [34,35].…”

“…Based on these genetic differences and the more aggressive behavior, some authors have suggested that an alternate mucinous phenotype-related pathway of carcinogenesis might exist and that MCA should be categorized and treated as a biological entity distinct from other colorectal adenocarcinomas [34,35]. Moreover, a recent study by Leopoldo et al [29] identified molecular alterations (e.g., MSI, hMLH1, p27) in subsets of MCAs associated with different clinicopathological and molecular characteristics and different outcomes, suggesting the existence of different subtypes of MCA.…”

Mucinous carcinoma of the rectum: a distinct clinicopathological entity

“…For example, there is a lower frequency of p53 mutations and conversely a higher frequency of K-Ras mutations [55]. p53 mutations are interesting as they are associated with rectal cancers but not common in mucinous subtype [56,57].…”