Clinicopathological features of gynaecological cancers in women with lynch syndrome.

Background: Women with an inherited germline mutation in a mismatch repair (MMR) gene have a recognized elevated risk of both endometrial (EC) and ovarian cancers (OC), together with the potential for an increased risk for cervical cancer (CC). There is modest information regarding the clinicopathological features of these cancers in this group. Method(s): We reviewed the pathology and clinical details for gynaecological cancers in women with a known pathogenic MMR mutation who were registered as part of the Colon Cancer Family Registry (CCFR). The features of these cancers were compared to literature reports of the same cancers in the general populations. Result(s): From 801 female carriers of a MMR mutation (312 MLH1, 391 MSH2, 66 MSH6 and 32 PMS2) recruited into the CCFR, 169 cases of EC were reported (48 MLH1, 98 MSH2, 21 MSH6 and 2 PMS2), 35 cases of OC (10 MLH1, 22 MSH2 and 3 MSH6) and 17 cases of CC (5 MLH1, 10 MSH2, 1 MSH6 and 1 PMS2) with pathology reports or medical records available for 96 ECs, 12 OCs and 8CCs. The mean age for diagnosis was younger than the general population for EC: 47.3 years (standard deviation, SD 8.2) p < 0.001, OC 47.0 years (SD7.5) p < 0.001 and CC 39.6 years (SD 9.8) p = 0.007. The predominant histology reported were: EC: endometrioid 63 (65%), OC: endometrioid 12 (60%) and for CC adenocarcinoma 7 (87.5%). Lower uterine segment involvement was seen in 24 cases (27%). Stage at diagnosis EC: I 69 (78.4%), II 15 (17%), III 5 (5.7%), and for OC I 12 (66.7%), II 4 (22.2%), III 3 (16.7%). Synchronous cancers were reported in 17 cases (1 CRC/EC/OC, 1 EC/OC/CC, 4 CRC/EC, 10 EC/OC, 1 CRC/CC). Expression for mismatch repair mutations for the concordant gene for all gynaecological cancer groups will also be presented. Conclusion(s): There are both significant differences and similarities between the cancers seen in association with Lynch Syndrome: in particular, OC appears to be predominantly early stage and endometrioid tumours, CC adenoca