Sporadic colorectal adenocarcinomas with high‐frequency microsatellite instability

Abstract

Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.

Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases

“…Moreover, preliminary data with a limited number of tumour samples indicated a good correlation of CLR with a high density of tumor-infiltrating cytotoxic (CD8 þ ) lymphocytes, supporting the hypothesis that CLR positivity is indeed associated with a cytotoxic antitumoural immune response. As in previous reports, we could show that the presence of a CLR was closely associated with a microsatellite unstable phenotype of colorectal cancer (Gafa et al, 2000). The strong antitumoural lymphoid reaction, which frequently occurs in MSI-H colorectal cancers, is commonly attributed to tumour-specific neopeptides generated during MSI-H carcinogenesis.…”

Hypermethylation of the hMLH1 promoter with absent hMLH1 expression in medullary-type poorly differentiated colorectal adenocarcinoma in the elderly

“…This result is in accord with that of other investigators. 4,10,14 Although the high incidence of absent hMLH1 expression was reported in poorly differentiated colorectal adenocarcinomas, 14 our results indicated that in poorly differentiated adenocarcinoma, the medullary-type carcinoma is primarily affected as compared with pleomorphictype carcinoma. In view of the histopathological type of tumor, we are the first to describe hypermethylation of the hMLH1 promoter in medullarytype carcinomas.…”

“…Thus, these findings indicate that medullary-and pleomorphic-type carcinomas differ not only in their clinicopathologic features but also in their molecular findings and therefore we hypothesize that both types of poorly differentiated adenocarcinomas have different pathways in carcinogenesis. 4,14 Medullary-type carcinomas in the elderly share clinicopathologic and biological features with those occurring in patients with hereditary nonpolyposis colorectal cancer: predominant occurrence in the proximal colon, large-sized tumors, expansive growth, prominent Crohn's-like lymphoid reaction, low incidence of lymph node or hematogenous metastasis, and favorable outcome. 22 Common features are tumor location, histology, and biological behavior while age, gender distribution, and the presence of extra-colorectal primary malignancies are different between the two.…”

“…4,10 Cancers with high levels of microsatellite instability are the hallmark of hereditary nonpolyposis colorectal cancer, and microsatellite instability occurs in 10-15% of sporadic colorectal carcinomas. Colorectal adenocarcinomas with microsatellite instability often show an absence of hMLH1 protein, [12][13][14] indicating that the tumor with microsatellite instability may be induced by an abnormality of the mismatch repair gene. A germline mutation has been detected in the mismatch repair gene in patients with hereditary nonpolyposis colorectal cancer, and hypermethylation has been found in the hMLH1 gene promoter in sporadic colorectal cancer.…”

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

“…So we were not able to determine whether these tumours showed partly chromosomic instability. MSI positive tumours have particular clinical and histopathological features (Lothe et al, 1993;Thibodeau et al, 1993Thibodeau et al, , 1998Kim et al, 1994;Risio et al, 1996;Rüschoff et al, 1997;Jass et al, 1998;Gafa et al, 2000). In our series, the different features associated with MSI status conformed with the characteristics described in the literature: the presence of a mucinous component, rather poor differentiation, a Crohn's like lymphoid stromal reaction and a trend towards a tumour of a larger size.…”