title: Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome.
abstract: 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.
authors: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
authors: Jenny
authors: J
authors: Mas-Moya
authors: Division of Gastroenterology, Department of Internal Medicine, Hereditary Tumor Program, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
authors: Beth
authors: B
authors: Dudley
authors: Division of Gastroenterology, Department of Internal Medicine, Hereditary Tumor Program, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
authors: Randall E
authors: RE
authors: Brand
authors: Division of Gastroenterology, Department of Internal Medicine, Hereditary Tumor Program, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
authors: Darcy
authors: D
authors: Thull
authors: Department of Internal Medicine, Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
authors: Nathan
authors: N
authors: Bahary
authors: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
authors: Marina N
authors: MN
authors: Nikiforova
authors: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213. Electronic address: pair@upmc.edu.
authors: Reetesh K
authors: RK
authors: Pai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000473:pathology*; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1
keywords: Colorectal carcinoma; Endometrial carcinoma; Lynch syndrome; Lynch-like syndrome; MSI; Mismatch repair protein