Pathological features and clinical behavior of Lynch syndrome-associated ovarian cancer

Objective Lynch syndrome (LS) is an inherited tumor predisposition condition caused by mutations in the mismatch repair (MMR) genes. Mutation carriers are at increased risk of various malignancies, including ovarian cancer (OC). Relatively little is known about the pathological features and clinical behavior of LS associated OC. Methods We analyzed the data of 1047 proven MMR mutated individuals from a prospectively maintained database at a large referral center for genomic medicine in the North West of England. Data were crosschecked with pathology reports, the National Cancer Registry and death certificates, where appropriate. Data from gynecological surveillance and risk reducing surgery were analyzed. Results We identified 53 cases of LSAOC in proven MMR mutated individuals. The cumulative risk of LSAOC was 20% at age 80 in those who retained their ovaries. LSAOC presented at an earlier age (average 51, range 24–70 years) than sporadic OC. The predominant histological subtype was endometrioid adenocarcinoma (53%). Most cases presented early (85% at stage I/II vs. 15% at stage III/IV, p
Highlights • Lynch syndrome-associated ovarian cancer (LSAOC) is rare and difficult to study. • This is the largest reported series of OC from proven Lynch syndrome carriers. • Endometrioid OC was most common, followed by high grade serous, clear cell and mixed histology. • Most LSAOC was detected at stage 1 and overall 5-year survival was excellent at 80%. • Surveillance found 2 LSAOC; 3 more were diagnosed following surgery for screen-detected endometrial cancer.