Minardi Daniele, Lucarini Guendalina, Milanese Giulio, Montironi Rodolfo, Di Primio Roberto
Dipartimento di Scienze Cliniche e Specialistiche - Sezione di Urologia, Università Politecnica delle Marche - Azienda Ospedaliero-Universitaria Ospedali Riuniti, via Conca, 71, Ancona, Italy.
Dipartimento di Scienze Cliniche e Molecolari - Sezione di Istologia, Università Politecnica delle Marche, Ancona, Italy.
Virchows Arch. 2017 Jul;471(1):99-105. doi: 10.1007/s00428-017-2143-x. Epub 2017 May 9.
BAP1 is a gene situated on chromosome 3p in a region that can be modified in renal cell carcinomas (RCCs). Mutations that cause loss of expression of BAP1 frequently occur in primary clear cell renal carcinoma (ccRCC). In a previous work, we observed that loss of nuclear BAP1 expression was crucial in ccRCC progression; in the current study, we investigated BAP1 expression in a large series of small conventional ccRCCs treated with partial nephrectomy, to assess a possible role as biomarker and the prognostic value in terms of patients' survival at long-term follow-up. One hundred sixty-two patients with single pT1 ccRCC were selected from those who underwent surgery at our Institute of Urology between 1987 and 2000. The features considered in this study were gender, age, tumor size, grade, incidence of metastasis, and patient-specific survival; they were correlated with immunohistochemical BAP1 nuclear expression in tumoral tissue. Median follow-up was 197.24 months (range 19 to 274); median survival was 125.34 months (range 5 to 274 months). None of our pT1 ccRCCs showed total loss of nuclear BAP1 staining; we found a significant negative correlation between nuclear BAP1 expression and tumor size and between nuclear BAP1 expression and grade. In small ccRCCs, nuclear BAP1 staining was not correlated with disease-specific 5-year survival.Our data confirm the established role of BAP1 as a tumor suppressor protein. This is the first report where BAP1 has been studied in pT1 ccRCC tumors, but nuclear BAP1 expression cannot help identify patients having high-risk disease in these patients.
BAP1是位于3号染色体p臂上的一个基因,该区域在肾细胞癌(RCC)中可发生改变。导致BAP1表达缺失的突变在原发性透明细胞肾细胞癌(ccRCC)中频繁出现。在之前的研究中,我们观察到细胞核BAP1表达缺失在ccRCC进展中起关键作用;在本研究中,我们调查了一系列接受部分肾切除术治疗的小的传统ccRCC中BAP1的表达情况,以评估其作为生物标志物的可能作用以及在长期随访中对患者生存的预后价值。从1987年至2000年在我们泌尿外科接受手术的患者中选取了162例单发pT1期ccRCC患者。本研究考虑的特征包括性别、年龄、肿瘤大小、分级、转移发生率和患者特异性生存情况;这些特征与肿瘤组织中BAP1细胞核免疫组化表达相关。中位随访时间为197.24个月(范围19至274个月);中位生存期为125.34个月(范围5至274个月)。我们所有的pT1期ccRCC均未显示细胞核BAP1染色完全缺失;我们发现细胞核BAP1表达与肿瘤大小以及细胞核BAP1表达与分级之间存在显著负相关。在小的ccRCC中,细胞核BAP1染色与疾病特异性5年生存率无关。我们的数据证实了BAP1作为肿瘤抑制蛋白的既定作用。这是首次在pT1期ccRCC肿瘤中研究BAP1,但细胞核BAP1表达无法帮助识别这些患者中的高危疾病患者。