Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival

Abstract

Colorectal carcinoma with microsatellite instability (MSI-H) has a characteristic clinicopathologic profile, typically forming right-sided, lymphocyte-rich tumors that are often mucinous. Mucinous histology in general has been linked to adverse prognosis in some studies, but not in others. MSI-H carcinoma, in contrast, has a better prognosis than microsatellite stable carcinoma in most studies. We assessed the relationship between MSI status, clinicopathologic features and outcome for 248 consecutive patients with resected mucinous carcinoma. All cases were reviewed to confirm mucinous histology. Immunohistochemical stains for DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 were performed on a representative block from each case. Tumors lacking expression of a mismatch repair enzyme were designated MSI-H; all others were classified as microsatellite stable. Age, sex, tumor size, site, grade, stage, growth pattern, Crohn's-like reaction, vascular invasion and number of tumor-infiltrating lymphocytes were evaluated without knowledge of MSI status or patient outcome. 72 (29.3%) mucinous carcinomas were MSI-H. Compared to microsatellite stable mucinous cancers, they were more likely to be right-sided (83.3 vs 48.6%, Po0.001), have a Crohn's -like reaction (65.7 vs 29.8%, Po0.001) and have many tumor infiltrating lymphocytes (72.2 vs 20.8%, Po0.001). MSI-H mucinous cancers presented more often as localized disease (66.7 vs 38.1%, Po0.001) and less often with lymph node (26.4 vs 44.9%) or distant (4.2 vs 16.5%) metastases. In univariate analysis, MSI had a favorable effect on ageadjusted survival (hazard ratio 0.597, P ¼ 0.02). In multivariate analysis, age, grade, Crohn's-like reaction and stage were independent predictors of survival, but MSI status was not. In conclusion, MSI-H mucinous carcinomas are right-sided, low-stage tumors with Crohn's-like reaction and tumor-infiltrating lymphocytes. The outcome for MSI-H mucinous carcinoma is better than that of microsatellite-stable mucinous carcinoma, but MSI status is not an independent predictor of survival.

Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma

“…In agreement with previous reports, 20,21 univariate analysis demonstrated that lower TNM stage and absence of vascular invasion had a favorable effect on survival of mucinous adenocarcinoma patients. Decreased invasion depth and no lymph node metastasis also had a favorable effect on survival of mucinous adenocarcinoma patients.…”

“…Higher TNM stage was an independent predictor of poor outcome in patients with mucinous adenocarcinoma, which is in accordance with other studies. 20,21 In univariate analysis, lower TNM stage had a favorable effect on survival of signet-ring cell carcinoma patients; this finding is consistent with other reports. 3,6 The vast majority of signet-ring cell carcinoma presents as a diffusely infiltrating carcinoma, which therefore is described by some authors as linitis plastica or lymphangiosis-type colorectal carcinoma.…”

“…These findings are in contrast to most studies that have shown a proximal colon location and a survival benefit for patients with high-frequency microsatellite instability mucinous adenocarcinoma over those with microsatellite stability mucinous adenocarcinoma. 20,21 However, a recent multivariate analysis indicated that microsatellite instability status of mucinous adenocarcinoma was not an independent predictor of survival, whereas older age, higher grade, higher stage, and absence of Crohn's-like infiltrate were independent predictors of poor outcome. 21 In signet-ring cell carcinoma, high-frequency microsatellite instability tumors were significantly more frequent in the proximal colon than in the distal colon; this finding is in agreement with a previous report.…”

“…20,21 However, a recent multivariate analysis indicated that microsatellite instability status of mucinous adenocarcinoma was not an independent predictor of survival, whereas older age, higher grade, higher stage, and absence of Crohn's-like infiltrate were independent predictors of poor outcome. 21 In signet-ring cell carcinoma, high-frequency microsatellite instability tumors were significantly more frequent in the proximal colon than in the distal colon; this finding is in agreement with a previous report. 6 There was no significant difference in overall survival between patients with high-frequency microsatellite instability and microsatellite stability signet-ring cell carcinomas, which is consistent with the result of a previous report.…”

A relação entre metástases em linfonodos regionais e fatores prognósticos no adenocarcinoma esporádico de intestino grosso

“…Em geral, os tumores com áreas mucoprodutoras usualmente são encontrados em estádios mais avançados de doença, com maior invasão dos tecidos periviscerais e metástases em linfonodos regionais mais freqüentemente. O prognóstico dos pacientes com adenocarcinoma colorretal está relacionado ao número de linfonodos regionais comprometidos por metástases e a profundidade de invasão da parede (6,9,14,16,17,18,19,20) . Os autores não encontraram associação significativa entre a presença de metástases em linfonodos regionais com idade (p=0,802), sexo (p=0,786), borda de invasão tumoral microscópica (p=0,180), presença de áreas mucoprodutoras (p=0,860), grau de diferenciação tumoral (p=0,068) e tamanho tumoral (p=0,987).…”