Checkpoint kinase 1 protein as a diagnostic marker for pleural mesothelioma

Pleural mesothelioma (PM) is an aggressive malignancy that poses diagnostic challenges, particularly in cytological specimens. Checkpoint kinase 1 (CHK1); a pivotal mediator of genomic stability, has been identified as a promising therapeutic target. In this study, we investigate CHK1 protein expression in PM and evaluate its potential utility as a diagnostic biomarker.

This retrospective study included patients diagnosed with PM and control cases containing non-neoplastic mesothelial cells (NNMC). Tissue microarrays were immunostained for CHK1 protein. Diagnostic accuracy of CHK1 expression was assessed across tumor subtypes (epithelioid and nonepithelioid) and specimen types (cytology and histology), using dichotomized positivity. CHK1 expression levels were compared between tumor subtypes and specimen types using the histoscore method.

A total of 152 pm cases were included (cytology, n = 74; histology, n = 78), along with 33 cytological control cases. CHK1 expression significantly distinguishes PM from NNMC (P < 0.001), with ranging sensitivities (67%-100%) and specificities (75%-91%), depending on subcellular localization and tumor subtypes. Nuclear expression contributes to high sensitivity whereas cytoplasmic expression confers the highest specificity. The histoscores were higher for total and nucleus in histology compared to cytology, while no significant differences in expression were observed between epithelioid and nonepithelioid PM.

Immunohistochemical assessment of CHK1 expression may be useful for distinguishing PM from NNMC. Robust diagnostic sensitivity was observed across both epithelioid and nonepithelioid PM, independent of specimen type. These support CHK1 as a potential pan-mesothelioma diagnostic biomarker. Further validation is warranted in larger, independent cohorts.