Isolated MLH1 Loss by Immunohistochemistry Because of Benign Germline

Dustin E Bosch; Matthew M Yeh; Stephen J Salipante; Angela Jacobson; Stacey A Cohen; Eric Q Konnick; Vera A Paulson

doi:10.1200/PO.22.00227

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Isolated MLH1 Loss by Immunohistochemistry Because of Benign Germline

Journal article

Open access

Peer reviewed

Isolated MLH1 Loss by Immunohistochemistry Because of Benign Germline

Dustin E Bosch, Matthew M Yeh, Stephen J Salipante, Angela Jacobson, Stacey A Cohen, Eric Q Konnick and Vera A Paulson

JCO precision oncology, Vol.6, e2200227

08/31/2022

DOI: 10.1200/PO.22.00227

PMCID: PMC9489174

PMID: 36044719

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Abstract

Mismatch repair (MMR) immunohistochemistry (IHC) is frequently used to inform prognosis, select (immuno-)therapy, and identify patients for heritable cancer syndrome testing. However, false-negative and false-positive MMR IHC interpretations have been described.Following identification of discordant MMR IHC and DNA-based microsatellite instability testing in a patient with colorectal carcinoma, we retrospectively reviewed institutional archives to identify patient samples with similar discrepancies.We report a patient with metastatic colorectal carcinoma who initially received immunotherapy on the basis of apparent isolated loss of MLH1 by IHC; notably,This study confirms that rare germline polymorphisms can result in incorrect IHC results, potentially affecting selection of optimal therapy and the decision to pursue germline testing. This case further highlights the need for expert molecular pathologic review and communication between clinical and molecular oncology teams.

Immunohistochemistry

MutL Protein Homolog 1

Microsatellite Instability

Humans

Female

Colorectal Neoplasms

Retrospective Studies

Endometrial Neoplasms

Germ Cells

Details

Title: Subtitle: Isolated MLH1 Loss by Immunohistochemistry Because of Benign Germline
Creators: Dustin E Bosch - University of Iowa
Matthew M Yeh - University of Washington School of Medicine
Stephen J Salipante - University of Washington School of Medicine
Angela Jacobson - University of Washington School of Medicine
Stacey A Cohen - University of Washington School of Medicine
Eric Q Konnick - University of Washington School of Medicine
Vera A Paulson - University of Washington School of Medicine
Resource Type: Journal article
Publication Details: JCO precision oncology, Vol.6, e2200227
DOI: 10.1200/PO.22.00227
PMID: 36044719
PMCID: PMC9489174
NLM abbreviation: JCO Precis Oncol
ISSN: 2473-4284
eISSN: 2473-4284
Publisher: ASCO
Language: English
Date published: 08/31/2022
Academic Unit: Pathology; Physics and Astronomy; Interdisciplinary Programs; Geographical and Sustainability Sciences
Record Identifier: 9984533284502771

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