Immunohistochemical Screening of Upper Tract Urothelial Carcinomas for Lynch Syndrome Diagnostics: A Systematic Review.

Abstract

OBJECTIVE:

To review the effect of universal screening of newly diagnosed upper tract urothelial carcinomas (UTUC) for mismatch repair (MMR) protein loss to aid in Lynch syndrome diagnostics.

MATERIALS AND METHODS:

Studies were identified through PubMed on December 1, 2021. Eligibility criteria were universal immunohistochemical analyses for at least 2 MMR proteins in unselected, consecutively collected UTUC cohorts. Exclusion criteria included reviews, case-reports, non-English language, and non-humans. Risk of bias was assessed using a modified Newcastle-Ottawa scale. Meta-analyses were performed to compare the association between clinical criteria and Lynch syndrome diagnoses.

RESULTS:

From 12 included studies, 1628 surgically removed UTUC from 1626 patients were screened for MMR protein loss. In 11 studies, 140 of the 1559 patients had tumors with loss (9.0%) with 80.7% showing loss of MSH2, MSH6, or both. In 7 studies, genetic testing confirmed Lynch syndrome diagnosis for 20 of 970 patients (2.1%). In 8 studies, 31 patients were given a clinical Lynch syndrome diagnosis (2.6%). In total, 51 assumed or verified Lynch syndrome patients were identified among 1087 patients (4.7%). Meta-analyses of 3 studies showed significant association between previous cancer diagnosis and Lynch syndrome-associated UTUC (P = .038).

CONCLUSION:

Despite the few studies conducted and lack of genetic testing, current data suggests that universal screening for MMR protein loss in UTUC may result in Lynch syndrome diagnoses in 4.7%. However, for the screening to be effective for Lynch syndrome diagnostics, follow-up investigations, such as genetic testing for MMR variants, are needed.

• Authors: Maria Rasmussen, Mia Gebauer Madsen, Christina Therkildsen
• Journal: Urology (Urology) Vol. 165 Pg. 44-53 (07 2022) ISSN: 1527-9995 [Electronic] United States
• PMID: 35217028 (Publication Type: Journal Article, Review, Systematic Review, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• MutL Protein Homolog 1

Topics

• Carcinoma, Transitional Cell (diagnosis, genetics)
• Colorectal Neoplasms, Hereditary Nonpolyposis (diagnosis, genetics, pathology)
• DNA Mismatch Repair
• Humans
• Immunohistochemistry
• MutL Protein Homolog 1 (analysis, genetics)
• Urinary Bladder Neoplasms