Abstract 16
Category: Clinical Science
At the end of the session, participants will be able to:
- Evaluate the efficacy of a 4 protein MMR IHC screening method for high-grade gliomas, with particular
attention paid to selective screening and screening PMS2 and MSH6 only. - Highlight the unique clinicopathological circumstances that might underlie MMR deficient tumours
COI Disclosure:
None to disclose.
Presenter
Jacob Houpt
Jacob A. Houpt 1, Lee Cyn Ang 1
1 Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, Canada.
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Medical Expert (the integrating role)
Routine Immunohistochemical Assessment of Mismatch Repair Proteins in High-Grade Gliomas: Retrospective Analysis and Clinical Implications
Abstract
Testing for deficiencies in mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6) via immunohistochemistry (IHC) has become a widely-adopted means of screening for tumour predisposition syndromes and for informing potential immunotherapeutic treatment options. While some centres rely on IHC for all 4 MMR proteins, others have relied on a more cost-effective means of screening only the secondary partner proteins PMS2 and MSH6 (as losses of MLH1/MSH2 are expected to result in degradation of PMS2/MSH6S). Just under 2 years ago, Cancer Care Ontario (CCO) began to fund routine MMR IHC testing on all high-grade gliomas (HGGs). London Health Sciences Centre has thus far tested 132 of these tumours for all 4 MMR proteins via IHC. Of these, 4 (approximately 3%) were found to have a loss of MMR immunopositivity (2 for MSH6, 2 for PMS2). These cases had particularly elevated nuclear pleomorphism when compared to most other HGGs and involved sporadic loss of MSH6 (with negative germline testing for Lynch syndrome), loss of MSH6 secondary to temozolomide chemotherapy (with intact MMR in the original tumour), and biallelic loss of PMS2 in the context of 2 cases of congenital mismatch repair deficiency syndrome (CMMRD). This IHC approach has been efficacious in contributing towards the diagnosis of tumour predisposition syndromes, identifying monoallelic versus biallelic loss of MMR proteins, and providing potential targets for immunomodulatory therapies. Furthermore, these results support the use of a two-antibody MMR IHC screening approach relying solely on MSH6 and PMS2.