ABCC2 expression in papillary renal cell carcinoma provides better prognostic stratification than WHO/ISUP nucleolar grade

• Published in: Human pathology Vol. 120; pp. 57 - 70
• Main Authors: Saleeb, Rola M., Brimo, Fadi, Gao, Yuan, Boulos, Carl, Kim, Sung Sun, Al Bashir, Samir, Husain, Arjumand, Rotondo, Fabio, Beharry, Vidya, Bjarnason, Georg A., Krizova, Adriana, Trpkov, Kiril, Yousef, George M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2022; Elsevier Limited
• Subjects: ABCC2; Automation; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - surgery; Cytoplasm; Disease-Free Survival; Drug transporters in cancer; Female; Genomes; Hospitals; Humans; Kidney cancer; Kidney Neoplasms - pathology; Laboratories; Male; Medical prognosis; Monoclonal antibodies; Morphology; Multidrug Resistance-Associated Protein 2 - metabolism; Papillary renal cell carcinoma; Pathology; Prognosis; Renal cell carcinoma; Resistance to therapy MRP2; Tumors; World Health Organization; ABCC2; Papillary renal cell carcinoma; Renal cell carcinoma; Drug transporters in cancer; Resistance to therapy MRP2
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2021.12.006

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-PRCC4: 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, hazard ratio: 5.008, 95% confidence interval: 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 ≤ 4 cm, 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 owing to its known implication in cancer biology and drug resistance. •ABCC2 is an active transporter normally expressed on brush border of renal tubules.•Previous studies: ABCC2 high expression in PRCC correlated with aggressive disease.•This study subdivides PRCC into 3 main groups based on ABCC2 expression.•PRCC groups significantly correlated with outcome and outperformed nucleolar grade.•ABCC2 confers anti-cancer therapy resistance and is a potential predictive marker.