Track: Clinical Studies

Abstract:

Muir-Torre syndrome (MTS) is a hereditary cancer predisposition syndrome associated with sebaceous gland tumors. Immunohistochemistry (IHC) testing for mismatch repair (MMR) protein loss in these tumors has been proposed as a screening tool for MTS, but its diagnostic accuracy has not been rigorously evaluated. We conducted a meta-analysis of 25 studies comprising 766 cases in which IHC was used to assess MMR protein expression in sebaceous tumors. Pooled accuracy estimates were calculated using bivariate analysis. The overall sensitivity was 0.85 (95% CI: 0.77–0.90), and specificity was 0.46 (95% CI: 0.27–0.66), with substantial heterogeneity across studies (I² = 78%). When the analysis was limited to studies that used germline mutation testing as the reference standard, sensitivity increased to 0.92, while specificity dropped markedly to 0.16. Hypothetical strategies to improve specificity such as restricting testing to patients under 60 years of age or to tumors arising outside the head and neck area led to gains in specificity but significant losses in sensitivity. A two-antibody IHC panel targeting MSH6 and PMS2 performed comparably to the full four-antibody panel (MLH1, MSH2, MSH6, and PMS2). These findings indicate that while IHC can differentiate sporadic from MTS-associated sebaceous tumors, its low specificity limits its utility as a screening tool. Restricting testing by age or tumor location may reduce false positives, but the associated loss in sensitivity undermines its effectiveness for screening purposes.

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Allison Swanson