Characteristics of Lynch Syndrome Associated Ovarian Cancer

Lynch syndrome (LS), an autosomal dominant tumor syndrome, is associated with increased risk of cancer. Most inherited endometrial cancers are caused by this syndrome. Only a minority of inherited ovarian cancers is causally related to LS; most inherited ovarian cancers are caused by a germline mutation in a BRCA1 or BRCA2 gene. The cumulative lifetime risk of ovarian cancer among women with LS varies between 6% and 12%; the reported mean age at diagnosis is approximately 45 years. The benefit of surveillance for ovarian cancer in LS has not been established. Only a few small surveillance studies have been conducted in women with LS; clinical and histopathologic characteristics of ovarian cancer in these women are unclear. Ovarian cancer develops at an early age in women with LS, usually at an early stage, and with a wide age range at onset.

The aim of this cohort study was to investigate the clinical and histopathologic characteristics of LS-associated ovarian cancer and the role of surveillance in the early detection of these cancers. Two prospective cohorts were used to identify ovarian cancer in women with LS. The first was derived from the Dutch Lynch Syndrome Registry (DLSR) between 1987 and 2016, and the second was from the Family Cancer Clinic at the University Medical Center Groningen (UMCG) between 1993 and 2016.

Data were collected on age at diagnosis, mutation type, International Federation of Gynecology and Obstetrics stage, histological type, treatment, follow-up, and gynecological surveillance.

Overall survival was defined as the interval from the date of diagnosis of ovarian cancer to the date of death from the disease.

A total of 53 LS-associated ovarian cancers were identified: 46 (6%) of 798 women in the DLSR and 7 (9%) of 80 in the UMCG cohort. The median age at diagnosis for LS-associated ovarian cancer was 46 years with a wide age range (20–75 years). The most frequent histopathologic types reported were endometrioid (n = 21 [40%]) and serous carcinoma (n = 19 [36%]). Most tumors (87% [46/53]) were diagnosed at an early stage (International Federation of Gynecology and Obstetrics stage I/II). Seventy-seven percent of the patients (46/53) were diagnosed with ovarian cancer before LS was diagnosed. Ovarian cancer developed in the other 23% (12/53) after starting annual gynecological surveillance for LS; 3 of these cancers were screen detected in asymptomatic women. Overall survival was 83% after a mean follow-up of 136 months.

Lynch syndrome–associated ovarian cancer may develop at a young age, with a wide age range at onset. It is most often diagnosed at an early stage, not attributable to annual gynecological surveillance, and often has an endometrioid or serous histology with a relatively good overall survival.