Examining patterns of genetic evaluation as well as the prevalence of tumor Mismatch Repair Deficiency or Microsatellite Instability and Lynch Syndrome in Women with Endometrial Cancer in New Orleans

ObjectivesFor synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests.Methods30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing.ResultsOf 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a PMS2 pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium.ConclusionsThere was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.

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Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome)

The Application of Clinical Genetics ◽

10.2147/tacg.s48625 ◽

2014 ◽

pp. 183 ◽

Cited By ~ 5

Author(s):

Aung Ko Win ◽

Daniel Buchanan ◽

Christophe Rosty ◽

Mark Clendenning ◽

Amanda Spurdle

Keyword(s):

Colorectal Cancer ◽

Endometrial Cancer ◽

Lynch Syndrome ◽

Mismatch Repair ◽

Mismatch Repair Deficiency ◽

Repair Deficiency ◽

Clinical Problems

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Colorectal Carcinomas With Isolated Loss of PMS2 Staining by Immunohistochemistry

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0156-oa ◽

2018 ◽

Vol 142 (4) ◽

pp. 523-528 ◽

Cited By ~ 8

Author(s):

Lindsay Alpert ◽

Reetesh K. Pai ◽

Amitabh Srivastava ◽

Wendy McKinnon ◽

Rebecca Wilcox ◽

...

Keyword(s):

Lynch Syndrome ◽

Microsatellite Instability ◽

Mismatch Repair ◽

Germline Mutation ◽

Clinicopathologic Features ◽

Colorectal Carcinomas ◽

Limited Information ◽

Mismatch Repair Deficiency ◽

Repair Deficiency ◽

Disease Specific

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.

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