[1983] Should All Endometrial Tumors Be Tested for MSI by IHC? A Pilot Analysis

Amal Kanbour-Shakir, David J Dabbs, Rohit Bhargava, Esther Elishaev. Magee-Womens Hospital of UPMC, Pittsburgh, PA

Background: The lifetime risk for Human Non-Polyposis Colorectal Carcinoma (HNPCC) syndrome or Lynch Syndrome patients to develop endometrial cancer is 50-60% as compared to 2-3% in the general population. Microsatellite instability (MSI) is present in nearly all HNPCC patients and can be identified using polymerase chain reaction (PCR) assay. Immunohistochemical (IHC) staining for mismatch repair (MMR) protein expression (MLH1, MSH2, PMS2 and MSH6) provides similar information. Tumors with MSI or MMR protein deficiency have better prognosis and may respond differently to chemotherapy.
Design: We compared the rate of identifying possible Lynch Syndrome patients for 2 different time periods. Group 1 (February to July 2012): reflex MMR protein testing via IHC on patients 60 years and younger with non-serous morphology. Group 2 (August and September 2012): IHC reflex testing on all patients with endometrial carcinomas regardless of age and morphology, in order to identify all Lynch syndrome patients. PCR reflex testing for MSI were performed on all cases with indeterminate staining pattern by IHC. Cases were classified as showing MMR loss if they showed loss of protein on IHC or showed high MSI on PCR. The results from these 2 time periods were compared in this quality assurance study.
Results: A total of 42 cases were tested, 9 (21%) showed MMR protein loss. Twenty-six cases were tested prior to August 2012 with average of 4.3 cases per month and 16 cases were tested in August and September 2012 with an average of 8 cases per month. MMR protein loss was identified in 6 of 26 (23%) cases in group 1 and in 3 of 16 (19%) cases in group 2. The average age of patients with MMR loss was 53 years compared to 55 years for patient with preserved MMR proteins (p=0.5493). One patient in-group 2 was 64 years old. Eight of 9 (89%) tumors with MMR protein loss showed endometrioid morphology and one showed clear cell morphology. Of the 33 tumors with preserved MMR protein, 29 (88%) showed endometrioid morphology, and 1 each was serous, carcinosarcoma, and mixed endometrioid and clear cell carcinoma. Eight of 9 (88%) tumors with MMR loss were FIGO stage 1, and one was FIGO stage 2. The tumors with preserved MMR protein were also predominantly stage 1 (26/33, 79%). No statistical difference was identified with respect to stage (p=0.6622).
Conclusions: Universal MMR protein testing doubles the workload of pathology laboratory, but does identify patients with possible Lynch syndrome that are not normally suspected based on patient's age.
Category: Quality Assurance

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 243, Tuesday Morning


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