Angela Chou1,2,3,4, Christopher W Toon1,2,5, Adele Clarkson1,6, Amy Sheen1, Loretta Sioson1, Anthony J Gill1,2,6. 1. Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia. 2. University of Sydney, Sydney, NSW, Australia. 3. Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, NSW, Australia. 4. The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. 5. Histopath Pathology, Macquarie Park, NSW, Australia. 6. NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
Abstract
AIMS: Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within 1 year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help to 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 correlated significantly with poor overall survival in both univariate (median survival 7.6 versus 13.6 months; P = 0.001) and multivariate analysis [hazard ratio (HR): 1.632; 95% confidence interval (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 stratified patients further 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, patients with exceptionally prolonged survival can potentially be identified.
AIMS: Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within 1 year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help to 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 correlated significantly with poor overall survival in both univariate (median survival 7.6 versus 13.6 months; P = 0.001) and multivariate analysis [hazard ratio (HR): 1.632; 95% confidence interval (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 stratified patients further 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, patients with exceptionally prolonged survival can potentially be identified.
Authors: Peter W Szlosarek; Melissa M Phillips; Iuliia Pavlyk; Jeremy Steele; Jonathan Shamash; James Spicer; Sanjeev Kumar; Simon Pacey; Xiaoxing Feng; Amanda Johnston; John Bomalaski; Graeme Moir; Kelvin Lau; Stephen Ellis; Michael Sheaff Journal: JTO Clin Res Rep Date: 2020-09-03
Authors: Noémi De Wispelaere; Sebastian Dwertmann Rico; Marcus Bauer; Andreas M Luebke; Martina Kluth; Franziska Büscheck; Claudia Hube-Magg; Doris Höflmayer; Natalia Gorbokon; Sören Weidemann; Katharina Möller; Christoph Fraune; Christian Bernreuther; Ronald Simon; Christian Kähler; Anne Menz; Andrea Hinsch; Frank Jacobsen; Patrick Lebok; Till Clauditz; Guido Sauter; Ria Uhlig; Waldemar Wilczak; Stefan Steurer; Eike Burandt; Rainer Krech; David Dum; Till Krech; Andreas Marx; Sarah Minner Journal: PLoS One Date: 2022-07-21 Impact factor: 3.752