ERJ open research · 2026
Ki67 proliferation index augments two-tier tumour grade in prediction of survival and progression-free survival in epithelioid pleural mesothelioma.
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Lynch Geraldine A, Zhang Yu Zhi, Bhatt Nidhi, Charters Pia, Aujayeb Avinash, Walker Saru, Symonds Jenny, Clive Amelia O, Bhatnagar Rahul, Morley Anna, White Paul, Nicholson Andrew G, Maskell Nick A, Bibby Anna
Аннотация
BACKGROUND: Pleural mesothelioma (PM) is a fatal asbestos-related cancer with a poor and often uncertain prognosis. This study validates the histological proliferation marker Ki67 and evaluates whether its integration into the two-tier tumour grading system can improve prognostication in epithelioid PM.
METHODS: Patients with epithelioid PM were recruited from two longitudinal cohort studies from 2010-2023. Diagnostic biopsies were analysed by three pulmonary pathologists. Cox regression determined the relationship between covariables and outcomes. Pearson correlation assessed the association between Ki67 and two-tier grade. A prognostic model combining Ki67 and tumour grade was internally validated using bootstrapping.
RESULTS: 98 patients were recruited. Ki67 was strongly predictive of overall survival (OS) and progression-free survival (PFS) and correlated with two-tier tumour grade. 30% was the optimal cut-off, with Ki67 more strongly predictive of OS (hazard ratio (HR) 2.37, 95% CI 1.51-3.71) and PFS (HR 2.09, 1.35-3.23) than two-tier grade (HR 1.83, 1.13-2.97 and HR 1.70, 1.08-2.66, respectively). Combining Ki67 and two-tier grade improved prediction of OS and PFS compared with two-tier grade alone. Ki67 stratified patients within each tumour grade, with median survival in the lowest risk group (low Ki67, low grade) of 660.5 days (IQR 329-1297) and 300 days (IQR 124-366) in the highest risk group (high Ki67, high grade).
CONCLUSION: Ki67 is a valid surrogate for tumour grade with an optimal cut-off at 30%. Integrating Ki67 into the two-tier grading system enhances prognostic accuracy, improves outcome prediction and would reduce uncertainty for patients and clinicians.
METHODS: Patients with epithelioid PM were recruited from two longitudinal cohort studies from 2010-2023. Diagnostic biopsies were analysed by three pulmonary pathologists. Cox regression determined the relationship between covariables and outcomes. Pearson correlation assessed the association between Ki67 and two-tier grade. A prognostic model combining Ki67 and tumour grade was internally validated using bootstrapping.
RESULTS: 98 patients were recruited. Ki67 was strongly predictive of overall survival (OS) and progression-free survival (PFS) and correlated with two-tier tumour grade. 30% was the optimal cut-off, with Ki67 more strongly predictive of OS (hazard ratio (HR) 2.37, 95% CI 1.51-3.71) and PFS (HR 2.09, 1.35-3.23) than two-tier grade (HR 1.83, 1.13-2.97 and HR 1.70, 1.08-2.66, respectively). Combining Ki67 and two-tier grade improved prediction of OS and PFS compared with two-tier grade alone. Ki67 stratified patients within each tumour grade, with median survival in the lowest risk group (low Ki67, low grade) of 660.5 days (IQR 329-1297) and 300 days (IQR 124-366) in the highest risk group (high Ki67, high grade).
CONCLUSION: Ki67 is a valid surrogate for tumour grade with an optimal cut-off at 30%. Integrating Ki67 into the two-tier grading system enhances prognostic accuracy, improves outcome prediction and would reduce uncertainty for patients and clinicians.