Mismatch Repair Deficiency to Pre-screen for Lynch Syndrome in Ovarian Cancer

Dawn O'Shea

September 21, 2020

A new study suggests tumour mismatch repair deficiency identified by immunohistochemistry could be used to pre-screening women with ovarian cancer suspected of having Lynch syndrome.

The study, published in the  Journal of Medical Genetics,  evaluated tumour mismatch repair deficiency and prevalence of Lynch syndrome in high-risk women referred to the Manchester Centre for Genomic Medicine with ovarian cancer over the past 20 years.

Women with ovarian cancer diagnosed before the age of 35 years and/or with a suggestive personal or family history of Lynch syndrome cancers underwent tumour testing with immunohistochemistry for mismatch repair deficiency and, where indicated, MLH1 promoter methylation testing, followed by constitutional testing for Lynch syndrome.

In total, 261 ovarian cancers were tested and 27 (10.3%; 95% CI, 6.9%-14.7%) showed mismatch repair deficiency by immunohistochemistry.

Three of seven with MLH1 loss showed MLH1 promoter hypermethylation, and 18 of the remaining 24 underwent constitutional testing for Lynch syndrome.

A further 15 women with mismatch repair proficient tumours underwent constitutional testing because of a strong family history of Lynch syndrome cancers.

Pathogenic variants were identified in nine of 33 (27%) women aged 33-59 (median, 48) years who underwent constitutional testing, including one whose tumour was mismatch repair proficient.

Most Lynch syndrome tumours were of endometrioid histological subtype.

The authors say tumour mismatch repair deficiency identified by immunohistochemistry is a useful pre-screen for constitutional testing in women with ovarian cancer with personal or family histories suggestive of Lynch syndrome.

Crosbie EJ, Ryan NAJ, McVey RJ, Lalloo F, Bowers N, Green K, Woodward ER, Clancy T, Bolton J, Wallace AJ, McMahon RF, Evans DG. Assessment of mismatch repair deficiency in ovarian cancer. J Med Genet. 2020 Sep 11 [Epub ahead of print]. doi: 10.1136/jmedgenet-2020-107270. PMID: 32917768 View full text

This article originally appeared on Univadis, part of the Medscape Professional Network.


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