Immunohistochemical markers to diagnose primary squamous cell carcinoma of the lung: a meta-analysis of diagnostic test accuracy

BACKGROUND: Inconsistent diagnostic test accuracies of immunohistological staining for squamous cell carcinoma (SQC) of the lung have been frequently reported. There have been few meta-analyses of the diagnostic accuracies of the immunohistochemical markers. METHODS: A systematic review and meta-analysis were performed following standard guidelines for systematic reviews of diagnostic test accuracy. Immunohistochemical markers (p40, p63, CK5/6, and DSC3) were evaluated as index tests for SQC. The diagnostic odds ratio (DOR) was obtained by the DerSimonian–Laird variate model. Summary estimates of sensitivity and specificity were calculated using a bivariate model. The protocol registration ID is UMIN000041664. RESULTS: The meta-analysis included 85 of the 1353 first-screened articles. The total number of patients was 17,893, which consisted 6151 SQC cases and 11,742 non-squamous non-small-cell lung cancer cases. The DOR was better for p40 (377, 95% confidence interval (CI) = 213–644, I(2) = 0%) than for CK5/6 (120, 95% CI = 78–184, I(2) = 2.5%), p63 (70, 95% CI = 55–88, I(2) = 9.1%), and DSC3 (94, 95% CI = 35–250, I(2) = 3.7%). Summary estimates of sensitivity and specificity were followings: p40 sensitivity 0.92 (95% CI = 0.89–0.95), specificity 0.94 (95% CI = 0.93–0.96); p63 sensitivity 0.92 (95% CI = 0.90–0.94), specificity 0.83 (95% CI = 0.80–0.86); CK5/6 sensitivity 0.90 (95% CI = 0.87–0.93), specificity 0.91 (95% CI = 0.89–0.93); DSC3 sensitivity 0.81 (95% CI = 0.73–0.88), and specificity 0.95 (95% CI = 0.85–0.98). CONCLUSION: P40 had the best DOR to diagnose SQC in non-small-cell lung carcinoma. Despite its lower sensitivity, DSC3 had the best specificity among the four markers and might be useful to rule-in the diagnosis of SQC.