Minardi Daniele, Lucarini Guendalina, Milanese Giulio, Di Primio Roberto, Montironi Rodolfo, Muzzonigro Giovanni
Dipartimento di Scienze Cliniche e Specialistiche-Sezione di Urologia, Università Politecnica delle Marche-Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
Dipartimento di Scienze Cliniche e Molecolari-Sezione di Istologia, Università Politecnica delle Marche, Ancona, Italy.
Urol Oncol. 2016 Aug;34(8):338.e11-8. doi: 10.1016/j.urolonc.2016.03.006. Epub 2016 Apr 13.
BRCA1-associated protein 1 (BAP1) is a gene situated on chromosome 3p in a region that is deleted in more than 90% of renal cell carcinomas (RCCs). In the present study, we studied BAP1 immunohistochemical expression in a large series of conventional clear cell RCCs (ccRCCs) treated with radical nephrectomy; we assessed the prognostic value of their expression in terms of patients׳ survival at long-term follow-up.
A total of 154 consecutive patients with ccRCC were selected from a prospective database and considered for the study purpose; all patients were treated with radical nephrectomy and lymphadenectomy at our Institute of Urology between 1983 and 1985. The features considered in this study were tumor size, grade and stage, vascular and capsular invasion, incidence of metastasis, and patient-specific survival; all these parameters were correlated with immunohistochemical cytoplasmic and nuclear expression of BAP1 in tumoral tissue.
Median follow-up was 196.18 months and median survival was 125.34 months. Nuclear BAP1 expression showed a high frequency of loss in tumoral cells; nuclear BAP1-negative tumors had higher tumor size, higher Fuhrman grade, and higher stage, a greater amount of vascular and capsular invasion and a higher incidence of metastases. In multivariate analysis, pathological stage and nuclear BAP1 expression resulted independent prognostic factors.
We have demonstrated that nuclear BAP1 expression is a marker of prognosis in ccRCC, having an influence on cancer-specific survival. The clinical importance for BAP1 will be realized with the identification and application of targeted therapies and with individualized approaches in the adjuvant setting or in the metastatic setting or in both the settings.
乳腺癌1号关联蛋白1（BAP1）是位于3号染色体p区的一个基因，在超过90%的肾细胞癌（RCC）中该区域会发生缺失。在本研究中，我们研究了BAP1在接受根治性肾切除术的大量传统透明细胞肾细胞癌（ccRCC）中的免疫组化表达；我们评估了其表达在长期随访患者生存方面的预后价值。
从一个前瞻性数据库中选取了154例连续的ccRCC患者用于本研究；所有患者于1983年至1985年在我们的泌尿外科研究所接受了根治性肾切除术和淋巴结清扫术。本研究考虑的特征包括肿瘤大小、分级和分期、血管和包膜侵犯、转移发生率以及患者特异性生存；所有这些参数均与肿瘤组织中BAP1的免疫组化细胞质和细胞核表达相关。
中位随访时间为196.18个月，中位生存期为125.34个月。细胞核BAP1表达在肿瘤细胞中显示出高频率的缺失；细胞核BAP1阴性的肿瘤具有更大的肿瘤大小、更高的富尔曼分级和更高的分期、更多的血管和包膜侵犯以及更高的转移发生率。在多变量分析中，病理分期和细胞核BAP1表达是独立的预后因素。
我们已经证明细胞核BAP1表达是ccRCC预后的一个标志物，对癌症特异性生存有影响。随着靶向治疗的识别和应用以及在辅助治疗或转移治疗或两者中的个体化方法的应用，BAP1的临床重要性将得以体现。
