Mismatch Repair Protein Deficiency/Microsatellite Instability Is Rare in Cholangiocarcinomas and Associated With...

Area of Science:

• Oncology
• Gastroenterology
• Genetics

Background:

• Mismatch repair (MMR) deficiency is a key biomarker for immunotherapy response in various cancers.
• Lynch syndrome, caused by germline MMR gene mutations, is not typically associated with cholangiocarcinomas.
• Pembrolizumab is approved for solid tumors with MMR deficiency or high microsatellite instability.

Purpose of the Study:

• To investigate the prevalence and clinicopathological features of MMR deficiency in cholangiocarcinomas.
• To determine if MMR deficiency in cholangiocarcinoma warrants consideration for immunotherapy.

Main Methods:

• Analysis of 96 intra- and extrahepatic cholangiocarcinoma cases.
• Morphological assessment using Hematoxylin and Eosin (H&E) staining.
• MMR status determination via immunohistochemical staining and microsatellite instability testing for MMR-deficient samples.

Main Results:

• MMR deficiency was identified in 6% of cholangiocarcinoma samples.
• A nontypical infiltrating pattern of invasion was the strongest predictor of MMR deficiency (P < .0001).
• None of the patients with MMR deficiency had a personal history of Lynch syndrome-associated cancers.

Conclusions:

• Specific cholangiocarcinoma morphologies (solid, mucinous, signet-ring) should prompt MMR testing for immunotherapy eligibility.
• MMR deficiency in cholangiocarcinoma does not necessarily indicate Lynch syndrome.