The epithelioid, BAP1-negative and p16-positive phenotype predicts prolonged survival in pleural mesothelioma

Abstract

Aims

Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within one year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help guide treatment. We therefore sought to investigate the role of p16 immunohistochemistry (IHC) both alone and in combination with other markers as a potential predictor of prolonged survival in mesothelioma.

Methods and Results

P16 IHC was performed on unselected pleural mesotheliomas biopsied from 1991 to 2014. 153 of 208 (74%) cases were p16-negative which significantly correlated with poor overall survival in both univariate (median survival 7.6 v 13.6 months; p = 0.001) and multivariate analysis (HR 1.632; 95% CI 1.103-2.415; p = 0.014). Other independent factors associated with prolonged survival included loss of expression of BAP1, and epithelioid morphology.

We therefore further stratified patients based on these three independent prognostic variables and demonstrated an unusually prolonged survival in mesotheliomas which were epithelioid, BAP1 IHC negative and p16 IHC positive (12% of cases, median survival 31.7 months, p<0.0001).

Conclusions

In conclusion, p16 IHC is an independent prognostic biomarker in pleural mesothelioma. When used in combination with BAP1 IHC and morphological subtyping, which are also readily available in routine clinical care, patients with exceptionally prolonged survival can potentially be identified.

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