Papillary renal cell carcinoma (PRCC) classification has traditionally been divided into two histologic types, type 1 and type 2. A new biological stratification system has recently been proposed based on comprehensive morphologic and genomic analysis. The predominant molecular marker in this 4-tiered stratification is the renal drug transporter ABCC2. In this study, we assessed and validated the value of the biological grouping in a PRCC cohort of 176 patients, and provided a comprehensive assessment of clinicopathological variables. Tissue microarrays (TMAs) were constructed from nephrectomy specimens. The TMAs were stained with ABCC2 and GATA3 antibodies and the PRCC cohort was stratified into four groups PRCC1-4: PRCC1 25%; PRCC2 37%; PRCC3 36%; and PRCC4 2%. PRCC1 demonstrated lower disease stage (p=0.041) than PRCC2 and PRCC3. The biological stratification was significant on univariate analysis when analyzing both overall survival (p=0.039) and disease-free survival (p=0.011). The biological groups maintained the significance of predicting overall survival after adjusting for WHO/ISUP grade, age, pathological stage, and necrosis (p=0.049, HR: 5.008, 95%CI 1.007 to 24.909). In contrast,WHO/ISUP grade did not maintain its significance on multivariate survival-analysis. ABCC2 expression profile also separated cases < 4cm, based on disease free survival (p=0.038). None of the patients in the PRCC1 group died of disease during the follow-up period. The proposed biologic stratification adds molecular markers to the traditional morphologic assessment to better stratify patients' prognosis. ABCC2 expression can also potentially serve as a predictive biomarker due to its known implication in cancer biology and drug resistance.
Human pathology. 2021 Dec 24 [Epub ahead of print]
Rola M Saleeb, Fadi Brimo, Yuan Gao, Carl Boulos, Sung Sun Kim, Samir Al Bashir, Arjumand Husain, Fabio Rotondo, Vidya Beharry, Georg Bjarnason, Adriana Krizova, Kiril Trpkov, George M Yousef
Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, Unity Health Toronto/St. Michael's Hospital, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON; Ontario Institute for Cancer Research, ON. Electronic address: ., McGill University Health Center, The Department of Pathology, Montreal, Quebec., Department of Pathology, Eastern Health, Health Sciences Centre, St. John's, NL., Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, Unity Health Toronto/St. Michael's Hospital, Toronto, ON., Department of Pathology & Microbiology, Jordan University of Science and Technology, Irbid, Jordan., Chinook Regional Hospital, Lethbridge, Alberta., University of Toronto, Toronto, Ontario; The Division of Medical Oncology and Hematology., Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, Unity Health Toronto/St. Michael's Hospital, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON., Department of Pathology and Laboratory Medicine, Alberta Precision Laboratories and University of Calgary, Calgary, AB., Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, Unity Health Toronto/St. Michael's Hospital, Toronto, ON; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON; Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON.