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

Abstract

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.

• Authors: Bharat Rekhi, Santosh Menon, Kedar K Deodhar, Jaya Ghosh, Supriya Chopra, Amita Maheshwari
• Journal: Annals of diagnostic pathology (Ann Diagn Pathol) Vol. 47 Pg. 151558 (Aug 2020) ISSN: 1532-8198 [Electronic] United States
• PMID: 32619922 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• G-T mismatch-binding protein
• PMS2 protein, human
• Mismatch Repair Endonuclease PMS2
• MutL Protein Homolog 1

Topics

• Adult
• Aged
• Brain Neoplasms (complications)
• Cell Differentiation
• Chemoradiotherapy, Adjuvant (methods)
• Colorectal Neoplasms (complications)
• Colorectal Neoplasms, Hereditary Nonpolyposis (genetics, pathology)
• Combined Modality Therapy
• DNA Mismatch Repair (genetics)
• DNA-Binding Proteins (genetics)
• Endometrial Neoplasms (diagnosis, genetics, metabolism, therapy)
• Feasibility Studies
• Female
• Humans
• Hysterectomy (methods)
• Immunohistochemistry (methods)
• India (epidemiology)
• Lymphatic Metastasis (pathology)
• Microsatellite Instability
• Middle Aged
• Mismatch Repair Endonuclease PMS2 (genetics)
• MutL Protein Homolog 1 (genetics)
• Myometrium (pathology)
• Neoplasm Grading (methods)
• Neoplastic Syndromes, Hereditary (complications)
• Salpingo-oophorectomy (methods)
• Uterine Neoplasms (pathology)