Molecular characteristics of poorly differentiated adenocarcinoma and signet-ring-cell carcinoma of colorectum

Abstract

In a series of 45 poorly differentiated adenocarcinomas (por) and 7 signet‐ring‐cell carcinomas (sig) of the colorectum, K‐ras gene mutation, p53 immunostaining and microsatellite instability (MSI) were analyzed for a comparison with 46 cases of colorectal carcinomas of the well or moderately differentiated type (well/mod). In addition, the mutations of simple repeated sequences in the transforming‐growth‐factor‐β type‐II receptor (T β R‐II) gene and the BAX gene were analyzed as possible targets for DNA replication errors. Mutation of the K‐ras gene in the por, sig and well/mod specimens was detected in, respectively, 22%, 11% and 48%, positive immunostaining for p53 in 41.8%, 28.6% and 60.3%, and MSI in 36%, 30% and 4%. Frameshift mutation of the T β R‐II gene was detected in 27.5% of the por and none of the sig specimens, while corresponding figures for mutation of the BAX gene were 15.7% and 0%. Significant differences between the por and well/mod tumors were found in the occurrence of K‐ras mutation at codons 12 and 13, and MSI. Clinicopathologically, the tumor status of por with MSI was found to significantly correlate with the tumor's location in the proximal colon. In cases without MSI and sig, no frameshift mutation of either the T β R‐II or the BAX gene was found. These results suggest that poorly differentiated and signet‐ring‐cell carcinomas have a genetic background different from that of well or moderately differentiated carcinomas of the colorectum, and that DNA‐replication error is at least partly involved in the carcinogenesis of these specific types of colorectal carcinomas. Int. J. Cancer (Pred. Oncol.) 84:33–38, 1999. © 1999 Wiley‐Liss, Inc.

Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

“…The reported 5-year survival in the literature is 9-37%, [1][2][3][4][5][6][7][8][9][10] which is comparable to the 33% survival in this study. The literature contains limited data on the molecular features of signet ring cell carcinoma.…”

“…[1][2][3][4][5][6][7][8][9][10] By definition, 450% of tumor cells have signet ring cell morphology. 11 Signet ring histology is considered an independent adverse prognostic factor by the American Joint Committee on Cancer and the College of American Pathologists.…”

Defective mismatch repair in the pathogenesis of low-grade appendiceal mucinous neoplasms and adenocarcinomas

“…Tumors with defective MMR tend to occur in younger patients, more often occur in the proximal colon, are more often mucinous, and frequently show a Crohn's-like lymphoid infiltrate or tumor-infiltrating lymphocytes. [8][9][10][11][12][13][14][15][16][17][18][19][20] In our study, none of the mucinous carcinomas or LAMNs with extra-appendiceal spread (considered well-differentiated mucinous carcinoma by some) demonstrated defective MMR. Our results are similar to those of Kabbani et al 40 who were unable to demonstrate MSI in 30 appendiceal adenocarcinomas.…”

“…7 Several investigators have reported that colorectal carcinomas with defective MMR often show distinctive clinicopathologic features including location in the proximal colon, younger patient age, mucinous differentiation, and a host-immune response characterized by a Crohn's-like lymphoid reaction or tumor infiltrating lymphocytes. [8][9][10][11][12][13][14][15][16][17][18][19][20] Serrated colonic polyps (hyperplastic polyps, mixed hyperplastic and adenomatous polyps, and serrated adenomas), particularly right-sided ones, are also associated with defective MMR 2,21 and are regarded as the precursor lesions for colorectal carcinomas with MSI, thus forming the basis of a 'serrated pathway' of colorectal tumorigenesis. 21 Appendiceal carcinomas, in contrast to 'generic colorectal carcinoma', often show mucinous differentiation and are per-force right-sided.…”

Signet ring cell carcinoma of the colorectum: correlations between microsatellite instability, clinicopathologic features and survival

“…21 Many studies have demonstrated the aggressive behavior of signet ring cell carcinoma. [17][18][19][20][22][23][24][25] The American Joint Committee on Cancer (AJCC) and the College of American Pathologists accept signet ring histology to be an independent adverse prognostic factor. 26,27 This gives rise to a paradoxical situation: microsatellite instability-high colon cancers have favorable prognosis, but can often show signet ring morphology, a well-documented adverse prognostic factor.…”