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Abstract：
Chromophobe RCC (ChRCC) carries the best prognosis among all RCC subtypes, yet it lacks a proper grading system. Various systems have been suggested in the past, causing much controversy, and Avulova et al. recently proposed a promising four-tier grading system that takes into consideration tumor necrosis. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway plays a key role in ChRCC pathogenesis, highlighting its molecular complexity. The present retrospective study aimed to evaluate the prognostic factors associated with a more aggressive ChRCC phenotype. Materials and Methods: Seventy-two patients diagnosed with ChRCC between 2004 and 2017 were included in our study. Pathology reports and tissue blocks were reviewed, and immunohistochemistry (IHC) was performed in order to assess the expressions of CYLD (tumor-suppressor gene) and mTOR, among other markers. Univariate analysis was performed, and OS was assessed using the Kaplan-Meier method. Results: In our study, 74% of patients were male, with a mean age of 60 years, and the mean tumor size was 63 mm (±44). The majority (54%) were followed for more than 10 years at intervals ranging between 44 and 222 months. The risk of death was significantly higher for patients that were classified as Grade 4 in the Avulova system (HR: 5.83; 95% CI, 1.37-24.7; p: = 0.017). As far as the IHC is concerned, mTOR expression was associated with an HR of 8.57 (95% CI, 1.91-38.5; p = 0.005), and CYLD expression was associated with an HR of 17.3 (95% CI, 1.57-192; p = 0.02). Conclusions: In our study, the Avulova grading system seems to be positively correlated with OS in patients diagnosed with ChRCC. Furthermore, an elevated mTOR expression also shows a negative correlation with OS, whereas an elevated CYLD expression does not seem to exert a protective role. However, because only a small proportion (4.2%) of our patients died due to ChRCC, despite the long follow-up period, the results must be interpreted with caution. Further research is needed to validate our findings.
摘要：
嫌色细胞RCC（ChRCC）在所有RCC亚型中预后最好，然而，它缺乏适当的评分系统。过去已经提出了各种系统，引起很多争议，和Avulova等人。最近提出了一个有前途的四级分级系统，考虑到肿瘤坏死。哺乳动物雷帕霉素靶蛋白(mTOR)通路的失调在ChRCC发病机制中起关键作用,突出了它的分子复杂性。本回顾性研究旨在评估与更具侵袭性的ChRCC表型相关的预后因素。材料与方法：2004年至2017年间诊断为ChRCC的72例患者纳入本研究。病理报告和组织块进行审查，进行免疫组织化学（IHC）以评估CYLD（抑癌基因）和mTOR的表达，在其他标记中。进行了单变量分析，和OS使用Kaplan-Meier方法进行评估。结果：在我们的研究中，74%的患者为男性,平均年龄为60岁，平均肿瘤大小为63mm(±44)。大多数（54％）以44至222个月的间隔进行了超过10年的随访。在Avulova系统中被分类为4级的患者的死亡风险明显更高(HR:5.83;95%CI,1.37-24.7;p:=0.017)。就IHC而言，mTOR表达与8.57的HR相关（95％CI，1.91-38.5；p=0.005），CYLD表达与17.3的HR相关（95％CI，1.57-192；p=0.02）。结论：在我们的研究中，在诊断为ChRCC的患者中，Avulova分级系统似乎与OS呈正相关。此外，mTOR表达升高也与OS呈负相关，而CYLD表达升高似乎并不发挥保护作用。然而,因为只有一小部分（4.2%）的患者死于ChRCC，尽管随访时间长,必须谨慎解释结果。需要进一步的研究来验证我们的发现。
