Papillary renal cell carcinoma (PRCC) histologic subtyping is no longer recommended in the 2022 WHO classification. Currently, WHO/ISUP nucleolar grade is the only accepted prognostic histologic parameter for PRCC. ABCC2, a renal drug transporter, has been shown to significantly predict outcomes in PRCC. In this study we evaluated the prognostic significance of ABCC2 IHC staining patterns in a large, multi-institutional PRCC cohort and assessed the association of these patterns with ABCC2 mRNA expression.
We assessed 254 PRCCs for ABCC2 IHC reactivity patterns that were stratified into negative, cytoplasmic, brush-border <50%, and brush-border ≥50%. RNA in situ hybridization (ISH) was used to determine the transcript level of each group. Survival analysis was performed with SPSS and GraphPad software. RNA-ISH showed that the ABCC2 group with any brush-border staining was associated with a significant increase in the transcript level, when compared to the negative/cytoplasmic group (P = 0.034). Both ABCC2 groups with brush-border <50% (P = 0.024) and brush-border ≥50% (P < 0.001) were also associated with worse disease-free survival (DFS) in univariate analysis. Multivariate analysis showed that only ABCC2 IHC brush-border (<50% and ≥50%) reactivity groups (P = 0.037 and P = 0.003, respectively), and high-stage disease (P < 0.001) had a DFS of prognostic significance. In addition, ABCC2 brush-border showed significantly worse DFS in pT1a (P = 0.014), pT1 (P = 0.013), ≤4 cm tumour (P = 0.041) and high stage (P = 0.014) groups, while a similar analysis with high WHO/ISUP grade in these groups was not significant.
ABCC2 IHC brush-border expression in PRCC correlates with significantly higher gene expression and also independently predicts survival outcomes.
Histopathology. 2023 Sep 07 [Epub ahead of print]
Vincent Francis Castillo, Mehdi Masoomian, Kiril Trpkov, Michelle Downes, Fadi Brimo, Theodorus van der Kwast, George M Yousef, Abraam Zakhary, Fabio Rotondo, Gina Saad, Vy-Nhan Nguyen, Wondwossen Kidanewold, Catherine Streutker, Corwyn Rowsell, Malek Hamdani, Rola M Saleeb
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Department of Pathology and Laboratory Medicine, Alberta Precision Laboratories and University of Calgary, Calgary, AB, Canada., Anatomic Pathology, Precision Diagnostics & Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada., Department of Pathology, McGill University Health Center, Montreal, QC, Canada., Department of Laboratory Medicine, Unity Health Toronto, Toronto, ON, Canada., Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.