Identification of possible Lynch syndrome in endometrial carcinomas at a public hospital in South Africa

Abstract

Endometrial carcinomas are common malignancies worldwide. Microsatellite instability is often identified in endometrioid endometrial carcinomas (EECs) and in most Lynch syndrome (LS) associated tumours. The authors aimed to identify the number of EECs at a South African public hospital, using the four-mismatch repair immunohistochemical stains, which may suggest possible LS, for the period 2009–2015. Following ethical clearance, 145 cases of archived EEC underwent immunohistochemical testing for MLH1, MSH2, MSH6 and PMS2. Cases demonstrating loss of MLH1 staining were subjected to EpiTYPER for quantitative methylation of the MLH1 promoter region using the Agena MassARRAY® platform. Forty-one (28.28%) cases showed complete loss of tumour nuclei staining for ≥ 1 immunohistochemical stains. Twenty cases (13.79%) showed loss of MLH1/PMS2, 16 cases (11.03%) demonstrated isolated MLH1 loss and one case (0.69%) showed loss of MLH1, PMS2 and MSH6. Two cases showed isolated MSH6 loss and 2 cases showed loss of MSH2 and MSH6. Thirty-seven (90.24%) of 41 mismatch repair-deficient cases showed MLH1 loss. Most (83.78%) of these showed promoter hypermethylation, suggesting a sporadic occurrence of carcinogenesis. The patients from whom the two cases with isolated MSH6 loss, two cases with MSH2/MSH6 loss, and the six cases whereby MLH1 was not explained by methylation should be identified and offered genetic counselling with a view to possible germline mutation assessment as these patients are suspected of having Lynch syndrome. Thus, this study demonstrates a possible 10/145 (6.90%) patients who may have LS and require further testing and suggests a need to screen possible LS patients in the South African population.