Improving Renal Tumor Biopsy Prognostication With BAP1 Analyses

Abstract

Context.— Active surveillance of small renal masses highlights the need for accurate prognostication of biopsies. Objective.— To comprehensively evaluate the accuracy of biopsies in assessing known prognostic parameters including histologic subtype by comparison with subsequent nephrectomy samples. Design.— We retrospectively identified patients at University of Texas Southwestern Medical Center, Dallas, Texas, who had a biopsy for a renal mass between 2004–2018. Biopsy samples were evaluated for known prognostic factors such as tumor grade, necrosis, sarcomatoid/rhabdoid change, and BRCA1-associated protein-1 (BAP1) status, which we previously showed is an independent prognostic factor for clear cell renal cell carcinoma. Accuracy was determined by comparison with subsequent analyses of nephrectomy specimens. Statistical analyses were performed to assess biopsy accuracy and correlation with tumor size and pathologic stage. Results.— From 805 biopsies with a diagnosis of renal neoplasm, 178 had subsequent resection of the biopsied tumor. Concordance rate for histologic subtype was 96.9% (κ [w], 0.90; 95% CI, 0.82–0.99) and excellent for small renal masses (98.8%; κ [w], 0.97; 95% CI, 0.90–1). Amongst the prognostic variables evaluated, BAP1 immunohistochemistry in clear cell renal cell carcinoma had the highest agreement (94.8%; κ [w], 0.83; 95% CI, 0.66–0.99). The presence of 1 or more aggressive features (grade 3–4, tumor necrosis, BAP1 loss, sarcomatoid/rhabdoid change) in a biopsy significantly correlated with pT stage (P = .004). Conclusions.— Biopsy analyses showed high accuracy for subtyping renal tumors, but it underestimated several poor prognostic features. Addition of BAP1 for clear cell renal cell carcinoma may increase prognostic accuracy. If validated, routine incorporation of BAP1 immunohistochemistry in clear cell renal cell carcinoma biopsies may refine prognosis and aid in the selection of patients for active surveillance.

Predicting Oncologic Outcomes in Small Renal Tumors

“…In our study evaluating patients with paired biopsies and subsequent resection of a renal mass, we found that while our ability to diagnose and render a specific histologic subtype on biopsy was excellent, biopsies underestimated histologic grade, necrosis, and sarcomatoid/rhabdoid features [32]. Among all prognostic variables evaluated, BAP1 status in ccRCC had the highest agreement [32]. Thus, needle biopsy can accurately represent the entire tumor for some (truncal) prognostic biomarkers such as BAP1, which could be used to better risk stratify patients with SRMs.…”

“…The finding that BAP1 is independently prognostic in SRM ccRCC may have practical application in particular since BAP1 status on biopsy is particularly accurate [32]. In our study evaluating patients with paired biopsies and subsequent resection of a renal mass, we found that while our ability to diagnose and render a specific histologic subtype on biopsy was excellent, biopsies underestimated histologic grade, necrosis, and sarcomatoid/rhabdoid features [32]. Among all prognostic variables evaluated, BAP1 status in ccRCC had the highest agreement [32].…”

Understanding Factors that Influence Prognosis and Response to Therapy in Clear Cell Renal Cell Carcinoma

“…BAP1 immunohistochemical results tend to be highly concordant with mutation status, which offers excellent practical applications. 81,91 Among known common prognostic variables, BAP1 mutation has consistently correlated with unfavorable prognostic factors 49,51 and, importantly, with sarcomatoid histology. 18,53 Further, BAP1 status has a high agreement between biopsies and resections [93.5%; kappa (w) 0.78; 95% CI 0.59-0.96].…”

“…18,53 Further, BAP1 status has a high agreement between biopsies and resections [93.5%; kappa (w) 0.78; 95% CI 0.59-0.96]. 91 Thus, determining BAP1 status in needle biopsy may improve the risk stratification of patients (Fig. 1B), especially for small renal masses where active surveillance may be a consideration.…”

Tumorigenesis Mechanisms Found in Hereditary Renal Cell Carcinoma: A Review

“…Due to its recent discovery, the full range of the syndrome and the penetrance of each lesion is unknown and additional associated tumors may include breast, neuroendocrine, thyroid, bladder and lung [ 158 , 159 ]. In addition, some advocate screening and reporting BAP1 status for renal biopsies showing ccRCC in that BAP1 mutation status can predict prognosis similar to grade and sarcomatoid/rhabdoid change [ 160 ].…”