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

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.