Abstract
The purpose of this study was to assess the prognostic value of programmed death ligand-1 (PD-L1) positivity in a non-clear cell renal cell carcinoma (non-ccRCC) cohort. PD-L1 expression was evaluated by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) specimens from 45 non-ccRCC patients with available tissue. PD-L1 positivity was defined as ≥1% of staining. Histopathological characteristics and oncological outcomes were correlated to PD-L1 expression. Cancer-specific survival (CSS) and recurrence-free survival (RFS) stratified by PD-L1 status were estimated using the Kaplan–Meier method. Median age was 58 years and median follow-up was 40 months. Non-ccRCC subtypes included sarcomatoid (n = 9), rhabdoid (n = 6), medullary (n = 2), Xp11.2 translocation (n = 2), collecting duct (n = 1), papillary type I (n = 11), and papillary type II (n = 14). PD-L1 positivity was noted in nine (20%) patients. PD-L1 positivity was significantly associated with higher Fuhrman nuclear grade (P = 0.048) and perineural invasion (P = 0.043). Five-year CSS was 73.2 and 83% for PD-L1 positive and negative tumors, respectively (P = 0.47). Five-year RFS was 55.6 and 61.5% for PD-L1 positive and negative tumors, respectively (P = 0.58). PD-L1 was expressed in a fifth of non-ccRCC cases and was associated with adverse histopathologic features. Expression of biomarkers such PD-L1 may help better risk-stratify non-ccRCC patients to guide treatment decisions and follow-up strategies.
Highlights
Renal cell carcinoma (RCC) is a lethal urologic malignancy accounting for 62,700 new cases and 14,240 deaths per year in the Unites States [1]
Newer treatments have mainly relied on the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin pathways, no durable responses have been observed to date [6, 7]
A hematoxylin and eosin (H&E) slide of each archival specimen was evaluated, and a block representing the overall tumor was chosen for Tissue microarray (TMA) preparation
Summary
Renal cell carcinoma (RCC) is a lethal urologic malignancy accounting for 62,700 new cases and 14,240 deaths per year in the Unites States [1]. PD-L1 expression in non-clear cell RCC mainstay of curative treatment recurrences can occur in 20–40% of cases [4]. RCC is considered to be immuno-responsive with cases of complete regression reported with high-dose immunotherapy [5]. Newer treatments have mainly relied on the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathways, no durable responses have been observed to date [6, 7]. In 2015, Nivolumab, an anti-programmed cell death-1 (PD-1) inhibitor, was approved for patients with advanced clear cell RCC (ccRCC) with failed prior anti-angiogenic therapy due to significantly higher objective response rates and an acceptable toxicity profile [9, 10]
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