Characterizing Gynecological Cancers with the Uncommon dMMR/MSS Phenotype in Lynch Syndrome Patients.

Mismatch-repair deficiency (MLH1, MSH2, MSH6, PMS2, EPCAM); unusual dMMR/MSS phenotype, mainly in MSH6 and PMS2 carriers.

Systematic review of Lynch syndrome-associated gynaecological cancers with a dMMR/MSS phenotype (mismatch-repair deficiency without microsatellite instability). Across 11 reports (2351 patients, 774 confirmed Lynch), 36 of 130 documented gynaecological cancers (27.7 %) were dMMR/MSS — 23 endometrial, 12 ovarian. This phenotype arose early (mean age 50.5 years for endometrial) and mainly in MSH6, then PMS2 carriers. No data on differential response to immune checkpoint inhibitors were available.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A useful spotlight on an underdocumented phenotype: the dMMR/MSS dissociation in Lynch carriers, which should not be misread as excluding the syndrome. The practical question — does response to immunotherapy differ from the dMMR/MSI-high phenotype? — remains open for lack of data. A reminder that MSI status alone does not rule out a germline origin.

Analysis by Dr Thibaut Benquey