Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences

• Published in: The American journal of pathology Vol. 145; no. 1; pp. 148 - 156
• Main Authors: Kim, H, Jen, J, Vogelstein, B, Hamilton, SR
• Format: Journal Article
• Language: English
• Published: United States ASIP 01-07-1994
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Carcinoma - genetics; Carcinoma - pathology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Replication - genetics; DNA, Neoplasm - genetics; DNA, Satellite - genetics; Female; Humans; Male; Middle Aged; Prospective Studies
• ISSN: 0002-9440; 1525-2191

DNA replication errors (RERs) in repeated nucleotide sequences due to defective mismatch repair genes have been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer syndrome (HNPCC). We detected RER in 18 cases (13%) in a prospective series of 137 sporadic stage II and III (Dukes' B and C) colorectal carcinomas. The clinical and pathological features of the RER-positive cases differed from those without RER. The patients with RER-positive cancers tended to be somewhat younger (60 +/- 5 years, range 22-83, versus 66 +/- 1, range 27-90, P = 0.2 with unequal variances) and had a marked preponderance of tumors proximal to the splenic flexure (17/18, 94%, versus 41/119, 34%, P < 0.0001). Only two RER-positive patients (11%) had a family history of colorectal cancer. In comparison to the 41 RER-negative proximal colonic cancers, RER-positive cancers had more frequent exophytic growth (P = 0.04), large size (P = 0.03), poor differentiation (P = 0.0004), extracellular mucin production (P = 0.003) and Crohn's-like lymphoid reaction (P = 0.003), and a trend toward less frequent p53 gene product overexpression by immunohistochemistry (3/17, 18%, versus 18/41, 44%, P = 0.06). We conclude that a subset of sporadic colorectal carcinomas has unique biological features that may indicate inherited germline mutation, de novo germline mutation, or somatic mutations of the mismatch repair genes involved in HNPCC.