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

Tajima, Yusuke; Eguchi, Hidetaka; Chika, Noriyasu; Nagai, Tatsuo; Dechamethakun, Sariya; Kumamoto, Kensuke; Tachikawa, Tetsuhiko; Akagi, Kiwamu; Tamaru, Jun‐ichi; Okazaki, Yasushi; Ishida, Hideyuki

doi:10.1093/jjco/hyy081

Cited by 11 publications

(32 citation statements)

References 40 publications

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“…Of these 9 (4%) were reported as isolated MLH1, 82 (38%) had MLH1/PMS2 loss, 2 (1%) had isolated MSH2, 54 (25%) had isolated MSH6 loss and 68 (32%) had MSH2/MSH6 loss. Reflex MLH1 promotor hypermethylation data was reported in nine studies 23‐26,32,33,71,75,76 . Of the 53 OCs with MLH1 or MLH1/PMS2 loss 40 (75%) were found to be hypermethylated.…”

Section: Resultsmentioning

confidence: 95%

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The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis

Atwal

Snowsill

Dandy

et al. 2022

Intl Journal of Cancer

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Ovarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five-year survival for OC is around 45% increasing the need for innovative treatments. Checkpoint inhibitors have shown significant clinical efficacy in mismatch repair deficient (MMRd) cancers and could be a powerful treatment in OC. However, their application in OC is limited due to the lack of data on the prevalence of MMRd.The aim of our study was to conduct a systematic review of the literature and metaanalysis to provide an accurate estimate of the prevalence of MMRd in OC. We followed PRISMA guidelines throughout. Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science followed by citation searching. Studies not written in English were excluded. All studies were reviewed by at least two independent reviewers. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I 2 score was used to assess heterogeneity across studies. In total 54 studies were included with 17 532 analyzed for MMRd. The overall proportions of MMRd by immunohistochemistry and microsatellite instability analysis were 6.7% and 10.4%, respectively. MMRd was reported in all histotypes of epithelial OC but was most common in endometrioid OC. We estimate that on average 46.7% (95% CI: 28.8-65.4) of ovarian carcinomas showing MMRd by IHC had a germline path_MMR variant identified. OC in those with Lynch syndrome seems to present at an earlier age and stage. Studies however were generally of low quality and there was a high degree of heterogeneity. A significant minority (up to 16%) of OC displays MMRd and, therefore, could be amenable to checkpoint inhibition therapy. However, the current literature base is of limited quality and therefore high-quality prospective studies exploring MMRd in OC with the use of multimodal testing are required. In addition, trials researching efficacy of checkpoint inhibition in MMRd OC are needed.

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Section: Resultsmentioning

confidence: 95%

“…Of the 53 OCs with MLH1 or MLH1/PMS2 loss 40 (75%) were found to be hypermethylated. Eighteen studies provided information on the FIGO stage in their MMRd IHC cohort 23,24,31‐34,36,37,39,45,47,49,53,55,60,61,71,76 . In total, 71 (38%) were stage I‐II and 118 (62%) were stage III‐IV.…”

Section: Resultsmentioning

confidence: 99%

The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis

Atwal

Snowsill

Dandy

et al. 2022

Intl Journal of Cancer

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“…It is considered that methylation is the cause of loss of MLH1 expression, which is observed in colorectal and uterine cancers, whereas loss of MSH2 expression may be due to somatic mutations in both alleles in addition to methylation. Tajima et al ( 44 ) reported that somatic mutations were also detected in both of these alleles in uterine carcinoma. In the present study, the five patients with loss of MMR protein expression did not survive and it was therefore impossible to perform an additional detailed genetic analysis.…”

Section: Discussionmentioning

confidence: 99%

Low prevalence of biliary tract cancer with defective mismatch repair genes in a Japanese hospital‑based population

et al. 2021

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“…Relatively new and with the understanding of its pathogenesis still evolving, the term LLS in association with CRC was first coined in 2013 [29] and, where it has not been described in patients with SBC, the term has come to be used for patients with LS-associated tumors such as CRC [14], epithelial ovarian cancer [30], sebaceous tumors [31], and upper urothelial cancer [32]. LLS may account for as many as 70% of all cases with suspected LS [29].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Molecular Characterization of Defective DNA Mismatch Repair in Small-bowel Carcinoma in a Japanese Hospital-based Population

Ito

Ishida

Suzuki

et al. 2020

J Anus Rectum Colon

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Objectives: To investigate the prevalence and molecular characteristics of defective DNA mismatch repair (dMMR) in small-bowel carcinoma (SBC) in a Japanese-hospital population. Methods: Immunohistochemistry was performed to evaluate the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) in formalin-fixed paraffin-embedded sections prepared from surgically resected primary SBCs from 30 patients during March 2002 to March 2017. Genetic testing for Lynch syndrome was performed in patients who demonstrated MMR protein loss. Results: Two of 30 patients (6.7%) demonstrated concomitant loss of MSH2/MSH6 protein expression. Further genetic testing identified a pathogenic MSH2 variant in one of these patients. Conclusions: The prevalence of dMMR SBCs in a Japanese hospital-based population seems lower than that reported in previous studies. To determine whether dMMR SBCs might be strongly linked to Lynch syndrome, there is a need for further investigation with a larger sample size.

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

Cited by 11 publications

References 40 publications

The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis

The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis

Low prevalence of biliary tract cancer with defective mismatch repair genes in a Japanese hospital‑based population

Prevalence and Molecular Characterization of Defective DNA Mismatch Repair in Small-bowel Carcinoma in a Japanese Hospital-based Population

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