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Prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancer in a Japanese hospital-based population

Japanese journal of clinical oncology, 2018-08, Vol.48 (8), p.728-735 [Peer Reviewed Journal]

ISSN: 1465-3621 ;EISSN: 1465-3621 ;DOI: 10.1093/jjco/hyy081 ;PMID: 29889250

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Title:
Prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancer in a Japanese hospital-based population
Author: Tajima, Yusuke ; Eguchi, Hidetaka ; Chika, Noriyasu ; Nagai, Tomonori ; Dechamethakun, Sariya ; Kumamoto, Kensuke ; Tachikawa, Tetsuhiko ; Akagi, Kiwamu ; Tamaru, Jun-Ichi ; Seki, Hiroyuki ; Okazaki, Yasushi ; Ishida, Hideyuki
Subjects: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asians ; Carcinoma, Ovarian Epithelial ; DNA Copy Number Variations - genetics ; DNA Methylation ; DNA Mismatch Repair - genetics ; Female ; Germ-Line Mutation - genetics ; Hospitals ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins - metabolism ; Neoplasms, Glandular and Epithelial - epidemiology ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - pathology ; Ovarian Neoplasms - epidemiology ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Prevalence ; Promoter Regions, Genetic ; Young Adult
Is Part Of: Japanese journal of clinical oncology, 2018-08, Vol.48 (8), p.728-735
Description: The prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancers in the Japanese population have scarcely been investigated. Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary epithelial ovarian cancers in patients who underwent oophorectomy at our institution between April 2005 and September 2014. Genetic and/or epigenetic alterations of the mismatch repair genes were investigated in patients with loss of any mismatch repair proteins in the tumor. There were 305 patients with a median age of 54 years (range, 18-83 years). Loss of expression in the ovarian tumor of one or more mismatch repair proteins was observed in 3 of the 305 patients (0.98%): 2 patients MLH1/PMS2 loss and 1 patient showed MSH2/MSH6 loss. Genetic testing of these three patients failed to reveal any pathogenic germline mutations of MLH1 or MSH2. One patient with MLH1/PMS2 loss showed hypermethylation of the promoter region of MLH1. Somatic mutations were found in each of the alleles of MLH1 (c.545dupG and deletion of exons 2-19) in the other patient with MLH1/PMS2 loss. In the patient with MSH2/MSH6 loss, two somatic mutations were detected in MSH2 (c.229_230delAG and c.1861C>T), although we could not determine whether these mutations were biallelic or not. The prevalence of defective mismatch repair epithelial ovarian cancer in the Japanese hospital-based population was extremely low. Molecular mechanism involved in such defective mismatch repair ovarian cancers seems to be epigenetic events through MLH1 promotor hypermethylation or somatically mutated mismatch repair genes without germline mismatch repair mutation.
Publisher: England
Language: English
Identifier: ISSN: 1465-3621
EISSN: 1465-3621
DOI: 10.1093/jjco/hyy081
PMID: 29889250
Source: GFMER Free Medical Journals
MEDLINE
Alma/SFX Local Collection

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Prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancer in a Japanese hospital-based population

ISSN: 1465-3621 ;EISSN: 1465-3621 ;DOI: 10.1093/jjco/hyy081 ;PMID: 29889250

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