Natural history of Von Hippel-Lindau disease-associated and sporadic clear cell renal cell carcinoma: a comparative study.

Jie Wang,Cuijian Zhang,Ziao Li,Liqun Zhou,Xuesong Li,Lin Yao,Kan Gong,Jianhui Qiu,Lei Zhang,Yucai Wu

doi:10.1007/s00432-021-03806-0

Abstract

To compare the tumor growth kinetics between sporadic clear cell renal cell carcinoma (ccRCC) and Von Hippel-Lindau disease-associated renal cell carcinoma (VHL-associated RCC). To analyze predictive markers for the growth rate of these two types of RCC. The clinical data of patients with renal tumors who received active surveillance were collected retrospectively. Immunohistochemical staining was utilized to analyze the expression levels of VHL, PBRM1, H3K36me3, and BAP1 in the postoperative specimens. The age of the VHL group was significantly younger than that of the sporadic group (P < 0.0001). The mean linear growth rate (LGR) was significantly faster in the sporadic group (P = 0.0004). The tumors of those in the sporadic group tended to have a higher histologic grade (P = 0.0011). In the sporadic group, tumor histologic grade was an independent predictor for rapid mean LGR (P = 0.0022). In the VHL group, initial maximal tumor diameter (MTD) was the only independent predictor for rapid mean LGR (P < 0.0001). Tumors with low VHL expression and negative PBRM1 expression showed a faster growth rate in the sporadic group (P = 0.001 and P = 0.008, respectively). The expression levels of the four biomarkers showed no impact on the tumor growth rate in the VHL group. Sporadic ccRCC grew faster than VHL-associated RCC. High histologic grade, low VHL expression and negative PBRM1 expression were predictors of faster growth in sporadic ccRCC. A large initial MTD was a predictor of faster growth for VHL-associated RCC.

Highlights

Renal cell carcinomas (RCCs) represent approximately 3% of all cancers, of which clear cell renal cell carcinoma is the most common histotype, representing 70–80% of cases(Deng and Melamed, 2012; Ljungberg et al, 2019)
Several researchers have assessed the natural history of sporadic clear cell renal cell carcinoma (ccRCC) and VHL-associated RCC, but no consensus has been reached on the tumor growth rate and its predictive markers(Crispen et al, 2009; Zhang et al, 2009; Staehler et al, 2010; Mason et al, 2011; Zhang et al, 2012; Zhang et al, 2015; Peng et al, 2019; Schuhmacher et al, 2019)
We found that the active surveillance (AS) time in the sporadic group was still longer than that in the VHL group when we included only patients with VHL-associated RCCs who underwent surgery; there was no significant difference in the final average tumor size between the sporadic group and the VHL group

Summary

Introduction

Renal cell carcinomas (RCCs) represent approximately 3% of all cancers, of which clear cell renal cell carcinoma (ccRCC) is the most common histotype, representing 70–80% of cases(Deng and Melamed, 2012; Ljungberg et al, 2019). Based on the above factors, urologists have paid increasing attention to researching the therapeutic effect of active surveillance (AS) of small RMs. To date, several researchers have assessed the natural history of sporadic ccRCC and VHL-associated RCC, but no consensus has been reached on the tumor growth rate and its predictive markers(Crispen et al, 2009; Zhang et al, 2009; Staehler et al, 2010; Mason et al, 2011; Zhang et al, 2012; Zhang et al, 2015; Peng et al, 2019; Schuhmacher et al, 2019). Sporadic ccRCC and VHL-associated RCC were analyzed together to compare the differences in growth rate between the two tumors. The differences in the expression levels of VHL, PBRM1, H3K36me and BAP1 between the two groups were measured by immunohistochemical staining, and their relationship with the tumor growth rate was analyzed

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Results

Conclusion