Nuclear PML expression as a prognostic biomarker in localised clear cell renal cell carcinoma
Sakari Kosola, Teemu D. Laajala, Iida Payne, Antti Kukkula, Lassi Luomala, Tuomas Mirtti, Kalle Mattila, Paula Vainio, Maria Sundvall, Panu M. JaakkolaAbstract
Objectives
To evaluate nuclear promyelocytic leukaemia protein (PML) expression as a prognostic biomarker in localised clear cell renal cell carcinoma (ccRCC), aiming to improve postoperative risk stratification.
Materials and methods
Two independent retrospective cohorts of patients undergoing surgery for localised ccRCC were analysed: an exploratory cohort ( n = 191; Turku University Hospital) and a validation cohort ( n = 173; Helsinki University Hospital). Patients underwent surgery between 2005 and 2014 and 2006–2013, respectively. Tissue microarrays from primary tumours were immunohistochemically stained and assessed for nuclear PML expression using both visual scoring and QuPath‐assisted image analysis. Clinical data at the time of surgery and follow‐up data were collected, with a median follow‐up of 8 years in the exploratory cohort and 9 years in the validation cohort. Associations between nuclear PML expression and recurrence‐free survival (RFS), cancer‐specific survival (CSS), overall survival (OS) and diagnostic histopathological characteristics were evaluated.
Results
High nuclear PML expression was associated with improved RFS ( p = 0.022) and CSS ( p = 0.027) in the exploratory cohort, with similar findings in the validation cohort in univariable analyses (both p < 0.0001). In the validation cohort, high nuclear PML expression remained independently associated with improved RFS (HR 0.38, 95% CI 0.21–0.70; p = 0.002), CSS (HR 0.30, 95% CI 0.13–0.68; p = 0.004) and OS (HR 0.34, 95% CI 0.18–0.68; p = 0.002) after adjustment for established histopathological risk factors in multivariable analyses.
Conclusions
Nuclear PML expression is associated with favourable outcomes in localised ccRCC and may provide additional prognostic information. Independent validation and mechanistic studies are warranted.