[1118] Conventional Screening Criteria May Miss a High Proportion of Lynch Syndrome Patients with Endometrial Carcinoma Due to PMS2 Loss

Bojana Djordjevic, Russell R Broaddus. University of Ottawa, Ottawa, ON, Canada; M.D. Anderson Cancer Center, Houston, TX

Background: Loss of mismatch repair (MMR) protein expression (MLH1, PMS2, MSH2 and MSH6) occurs in Lynch syndrome, while MLH1 loss can also be found in sporadic endometrial tumors due to promoter methylation. Experience with endometrial cancers with PMS2 loss is limited. In this study, we describe the clinical and pathological features of 7 such tumors, the largest case series to date.
Design: Using MMR immunohistochemistry, we investigated the following two different cohorts of endometrial cancer patients: 154 sequential patients, unselected for age or personal and family history of Lynch associated cancers, and 45 patients with a clinical suspicion of Lynch syndrome (age less than 50 and/or a relative with Lynch associated cancer).
Results: 7 patients with PMS2 loss and intact expression of other MMR proteins were identified. Their clinicopathologic characteristics are summarized below.

CaseAgePersonal Cancer HistoryFamily Cancer HistoryTumor Histotype and FIGO GradeStage
Unselected 187NoNoEndometrioid 21b
Unselected 245NoNoEndometrioid 21b
Unselected 375NoColon ca in mother at 92; Other Non-Lynch caEndometrioid 21a
Unselected 466NoNon-Lynch caEndometrioid 31b
Unselected 551NoNon-Lynch caEndometrioid 21a
Lynch Suspicious 158Non-Lynch caColon ca in mother at 58Endometrioid 21b
Lynch Suspicious 270NoColon ca in father at 66Endometrioid 23c

The average patient age was 64.6 years, with only one patient younger than 50. Only 3 patients had first degree relatives with colon cancer, with an average age of 72 years. In comparison with published data, MLH1, MSH2 and MSH6 mutation carriers had an average age of 45.8, 45.5 and 51.2 respectively at the time of endometrial cancer diagnosis, and first degree relatives with colon cancer at an average age of 48.0, 46.2 and 60.9 respectively. All tumors with PMS2 loss were of endometrioid histology. In contrast, non-endometrioid endometrial cancers with MLH1, MSH2 and MSH6 mutations have been reported.
Conclusions: Endometrial tumors with PMS2 loss have a predilection toward the endometrioid histotype. The patients tend to be older and either lack relatives with Lynch associated cancers or have relatives with colon cancer diagnosed later in life that may be confused with sporadic tumors. Therefore, Lynch syndrome patients with PMS2 abnormalities and endometrial cancer may be missed by screening criteria that use young patient age and family history as determinants for further testing.
Category: Gynecologic & Obstetrics

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 138, Wednesday Morning


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