Lindsay Alpert, Reetesh K Pai, Amitabh Srivastava, Wendy McKinnon, Rebecca Wilcox, Rhonda K Yantiss, Ramir Arcega, Hanlin L Wang, Marie E Robert, Xiuli Liu, Rish K Pai, Lei Zhao, Maria Westerhoff, Heather Hampel, Sonia Kupfer, Namrata Setia, Shu-Yuan Xiao, John Hart, Wendy L Frankel1. 1. From the Departments of Pathology (Drs Alpert, Setia, Xiao, and Hart) and Medicine (Dr Kupfer), University of Chicago, Chicago, Illinois; the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Reetesh Pai); the Department of Pathology, Brigham and Womens Hospital, Boston, Massachusetts (Dr Srivastava); the Departments of Medicine (Ms McKinnon) and Pathology and Laboratory Medicine (Dr Wilcox), University of Vermont Medical Center, Burlington; the Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York (Dr Yantiss); the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (Drs Arcega and Wang); the Department of Pathology, Yale-New Haven Hospital, New Haven, Connecticut (Dr Robert); the Department of Pathology, Cleveland Clinic, Cleveland, Ohio (Drs Liu and Rish Pai); the Department of Pathology, University of Alabama, Birmingham (Dr Zhao); the Department of Pathology, University of Washington, Seattle (Dr Westerhoff); and the Departments of Internal Medicine (Ms Hampel) and Pathology (Dr Frankel), The Ohio State University Wexner Medical Center, Columbus. Dr Rish Pai is now with the Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona. Dr Liu is now with the Department of Pathology, University of Florida, Gainesville. Dr Zhao is now with the Department of Pathology, Brigham and Womens Hospital, Boston, Massachusetts. Dr Westerhoff is now with the Department of Pathology, University of Michigan, Ann Arbor.
Abstract
CONTEXT: - Isolated loss of PMS2 staining is an uncommon immunophenotype in colorectal carcinomas, accounting for approximately 4% of tumors with microsatellite instability. Limited information regarding these tumors is available in the literature. OBJECTIVE: - To compare the clinicopathologic features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry to those with other forms of mismatch repair deficiency. DESIGN: - Ninety-three colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193 with other forms of mismatch repair deficiency were identified. Forty (43%) of the isolated PMS2 loss cases and 35 control cases (18%) had a known germline mutation or a clinical diagnosis of Lynch syndrome. RESULTS: - Overall, isolated PMS2-loss tumors occurred in significantly younger patients ( P < .001) and in fewer female patients ( P = .006). These tumors were significantly less likely to be right-sided ( P = .001), high-grade ( P = .01), or display histologic features of microsatellite instability ( P < .001). The isolated PMS2-loss group also exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95% CI, 1.41-6.85; P = .007). When the analysis was restricted to germline mutation/Lynch syndrome cases and controls, no significant differences were detected for age, sex, tumor location, tumor grade, histologic features, or distant metastases, although a trend toward increased odds of disease-specific death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04; P = .10). CONCLUSIONS: - Unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may demonstrate more aggressive behavior than other tumors with microsatellite instability, but larger studies are needed to investigate that possibility further.
CONTEXT: - Isolated loss of PMS2 staining is an uncommon immunophenotype in colorectal carcinomas, accounting for approximately 4% of tumors with microsatellite instability. Limited information regarding these tumors is available in the literature. OBJECTIVE: - To compare the clinicopathologic features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry to those with other forms of mismatch repair deficiency. DESIGN: - Ninety-three colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193 with other forms of mismatch repair deficiency were identified. Forty (43%) of the isolated PMS2 loss cases and 35 control cases (18%) had a known germline mutation or a clinical diagnosis of Lynch syndrome. RESULTS: - Overall, isolated PMS2-loss tumors occurred in significantly younger patients ( P < .001) and in fewer female patients ( P = .006). These tumors were significantly less likely to be right-sided ( P = .001), high-grade ( P = .01), or display histologic features of microsatellite instability ( P < .001). The isolated PMS2-loss group also exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95% CI, 1.41-6.85; P = .007). When the analysis was restricted to germline mutation/Lynch syndrome cases and controls, no significant differences were detected for age, sex, tumor location, tumor grade, histologic features, or distant metastases, although a trend toward increased odds of disease-specific death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04; P = .10). CONCLUSIONS: - Unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may demonstrate more aggressive behavior than other tumors with microsatellite instability, but larger studies are needed to investigate that possibility further.
Authors: Søren R Rafaelsen; Claus Dam; Chris Vagn-Hansen; Jakob Møller; Hans B Rahr; Mikkel Sjöström; Jan Lindebjerg; Torben Frøstrup Hansen; Malene Roland Vils Pedersen Journal: Curr Oncol Date: 2022-02-13 Impact factor: 3.109