Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India

• Published in: Annals of diagnostic pathology Vol. 47; p. 151558
• Main Authors: Rekhi, Bharat, Menon, Santosh, Deodhar, Kedar K., Ghosh, Jaya, Chopra, Supriya, Maheshwari, Amita
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2020
• Subjects: Endometrioid carcinoma; Microsatellite instability; Mismatch repair proteins; MMR deficient endometrial carcinoma; Uterine malignancy; Mismatch repair proteins; Microsatellite instability; Uterine malignancy; Endometrioid carcinoma; MMR deficient endometrial carcinoma
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2020.151558

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27–68 years(median = 53) and tumor size(n = 34) varied from 1.2–10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country. •This constitutes the first comprehensive study on MMR-deficient(D) endometrioid adenocarcinomas(EMAC) from our subcontinent.•Clinicopathologic features associated with MMRd are lower uterine segment involvement, high-grade, deeply infiltrative, heterogeneous EMACs; PR+ve, with wild-type p53.•Paired loss of MLH1/PMS2 was most frequent. MSH2 was the most frequently lost protein in patients with multiple cancers and with family history of cancer.•Tumors with lymphoepithelioma-like appearance and TILs are worthwhile testing for PDL1immunostaining.