Microsatellite instability as a reliable marker of coexisting endometrial cancer in atypical endometrial hyperplasia

Abstract

Background. Endometrial cancer (EC) dominates in the structure of gynecological cancer morbidity. There has been an increase in this nosology in women of reproductive age. The morphological precancerous form of endometrioid adenocarcinoma is endometrial intraepithelial neoplasia (EIN), or atypical endometrial hyperplasia (AEH), that is difficult to diagnose: there is a high percentage of underdiagnosis resulting in a wrong treatment strategy. To improve the accuracy of diagnosis, additional immunohistochemical markers are being studied that are not part of the physician»s routine practice. Extremely promising for the prognosis of endometrial malignancy is the assessment of the functioning of the genes of the DNA mismatched nucleotide repair system (DNA mismatch repair system, MMR).Aim. To assess the diagnostic value of (microsatellite instability, MSI) in patients with AEH to rule out coexisting endometrial cancer.Materials and methods. The study includes 72 histological samples: 36 cases of EIN and 36 cases of EC, 14 of which were combined with EIN. To assess the microsatellite status, immunohistochemical staining of specimens was done with the identification of 4 markers, i. e. MLH1, PMS2, MSH2, MSH6. Results. It was found that out of 36 cases of EIN, only one sample showed loss of the PMS2 and MLH1 genes, which amounted to 3 %; the remaining EIN samples showed microsatellite stability. In 5 (36 %) out of 14 cases of combined EC and EIN pathology, MSI/dMMR was identified. Eight (36 %) out of 22 EC samples were found to have MMR deficiency. Loss of PMS2 increases the likelihood of being classified as EC 9-fold (odds ratio 9.1). With that, the presence of foci of adenocarcinoma in the case of AEH if MSI is confirmed can be asserted with a probability of 93 %. The detection of MSI in a histological sample is more often associated with the presence of EC, while the loss of the PMS2 and/or MLH1 genes increases the likelihood of a cancer diagnosis. If during additional immunohistochemical analysis a loss of these genes is observed, then EC can be diagnosed, even with an ambiguous histological pattern.Conclusion. Detection of MSI/dMMR in AEH indicates the presence of foci of coexisting endometrioid adenocarcinoma with an extremely high degree of probability. Detection of MSI/dMMR in the treatment of EC is advisable at the stage of diagnosis.