Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

ObjectiveHeredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized.MethodsWe characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families.ResultsIn total, 63 epithelial ovarian cancers developed at mean 48 (range 30–79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed.ConclusionThe combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.

Research highlights
► Lynch syndrome-associated ovarian cancer develops at early age (mean 48 years) with half of the tumors diagnosed at early stage and an overrepresentation of endometrioid (35%) and clear cell (17%) histologies.
► MMR gene mutations affect MSH2 in 49%, MSH6 in 33% and MLH1 in 17% with immunohistochemical loss of MMR protein staining in 92%.