Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome

• Published in: Human pathology Vol. 46; no. 11; pp. 1616 - 1625
• Main Authors: Mas-Moya, Jenny, MD, Dudley, Beth, MS, Brand, Randall E., MD, Thull, Darcy, MS, Bahary, Nathan, MD, PhD, Nikiforova, Marina N., MD, Pai, Reetesh K., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015; Elsevier Limited
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult; Aged; Cloning; Colleges & universities; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology; Deoxyribonucleic acid; DNA; DNA Mismatch Repair; Endometrial carcinoma; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Female; Genetic counseling; Germ-Line Mutation; Humans; Lymphocytes; Lynch syndrome; Lynch-like syndrome; Male; Microsatellite Instability; Middle Aged; Mismatch repair protein; Mortality; MSI; Mutation; MutL Protein Homolog 1; Nuclear Proteins - genetics; Pathology; Polymerase chain reaction; Promoter Regions, Genetic; Protein expression; Proteins; Proto-Oncogene Proteins B-raf - genetics; Tumors; Young Adult; MSI; Endometrial carcinoma; Lynch-like syndrome; Colorectal carcinoma; Mismatch repair protein; Lynch syndrome
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2015.06.022

Summary Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinomas identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathological features of colorectal and endometrial carcinomas in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified 356 (10.6%) of 3352 patients with colorectal carcinoma and 72 (33%) of 215 patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%; P < .002). All patients with colorectal carcinomas demonstrating isolated loss of MSH6 expression had Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome–associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%; P = .04). There were no significant differences in clinicopathological variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome–associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor.