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.
|Case||Age||Personal Cancer History||Family Cancer History||Tumor Histotype and FIGO Grade||Stage|
|Unselected 1||87||No||No||Endometrioid 2||1b|
|Unselected 2||45||No||No||Endometrioid 2||1b|
|Unselected 3||75||No||Colon ca in mother at 92; Other Non-Lynch ca||Endometrioid 2||1a|
|Unselected 4||66||No||Non-Lynch ca||Endometrioid 3||1b|
|Unselected 5||51||No||Non-Lynch ca||Endometrioid 2||1a|
|Lynch Suspicious 1||58||Non-Lynch ca||Colon ca in mother at 58||Endometrioid 2||1b|
|Lynch Suspicious 2||70||No||Colon ca in father at 66||Endometrioid 2||3c|