Mismatch repair deficiency in cholangiocarcinoma.

2018 
269Background: Cholangiocarcinoma (CC) is a fatal malignancy with an unmet treatment need. With the approval of immunotherapy for solid tumors with mismatch repair (MMR) deficiency, there is a renewed interest in MMR testing. Little is known about the incidence of MMR deficiency in CC or its correlation to survival, immune cell infiltration, PD-L1 and other proteins expressed in CC such as mesothelin. Methods: CC tumors were identified from patients treated at the University of Virginia from 2000-2014. Tissue microarrays (TMAs) were constructed of 3-4 cores from each tumor and were stained by immunohistochemistry for MMR genes (MLH1, PMS2, MSH2, MSH6), mesothelin, PD-L1 and immune cells. TMAs were scanned using the Leica SCN400 and analyzed using the Digital Image Hub software. Stain intensity thresholds for defining positive cells were determined by two users and recorded as an average of all cores from each tumor. Mesothelin and PD-L1 expression were measured as a percentage of positive tumor cells. Cor...
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