The impact of immunohistochemical expression of nitric oxide synthases on clinical and pathological features of renal cell carcinoma.

PURPOSE: To evaluate the immunohistochemical expression of nitric oxide synthase (NOS) types 1, 2, and 3 in intratumoral and non-neoplastic samples of renal cell carcinoma (RCC) and correlate it with the clinical and pathological features of this malignancy. METHODS: We analyzed 110 patients with RCC underwent radical nephrectomy (RN) or partial nephrectomy (PN) by streptavidin-biotin peroxidase method, tissue microarray, and digital microscopy. As endpoints, NOS expression was correlated with pathological features, overall survival (OS), and cancer-specific survival (CSS). RESULTS: Non-neoplastic samples had higher NOS3 and lower NOS 2 levels than RCC tissues. Greater expression of all NOS isoforms was associated with larger tumors. High NOS1 expression correlated with microscopic venous invasion (MVI) (p = 0.046) and lymph node metastases (p = 0.007). High NOS2 expression was linked to MVI, more RN performed, and male gender (p = 0.035, p = 0.003, and p = 0.027, respectively). High NOS3 expression correlated with lymph node metastases (p = 0.039), microlymphatic invasion (p = 0.029), invasion of the renal pelvis and ureter (p = 0.004), RN (p = 0.003), and shorter OS (58.1 vs. 79.4 % respectively, p = 0.033) by univariate analysis. DFS was not influenced by any NOS isoform. By multivariate analysis, the risk factors for death were TNM stages III and IV (hazard ratio [HR] = 4.5), high Fuhrman's grade (HR = 2.9), Karnofsky performance status ≤80 (HR = 2.5), progression (HR = 5.5), and recurrence (HR = 6.3). Stage III disease was an independent risk factor for recurrence (HR = 9.5). CONCLUSIONS: High NOS expression in RCC is associated with a poor prognosis and larger tumors. NOS3 influences OS by univariate analysis.

Prognostic impact of concomitant loss of PBRM1 and BAP1 protein expression in early stages of clear cell renal cell carcinoma.

PURPOSE: To evaluate the prognostic impact of immunohistochemical expression of BAP1 and PBRM1 in patients with early stage (pT1-pT2N0M0) clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: A total of 441 consecutive patients treated surgically for stages I and II (TNM-AJCC 2010) ccRCC between 1990 and 2016 were selected. All cases were reviewed for uniform reclassification and the most representative tumor areas were selected for the construction of a tissue microarray. Sixty-two patients had frozen tumoral tissue available in the tumor bank of our institution for quantitative real-time reverse transcriptase polymerase chain reaction analysis. RESULTS: Of the 441-immunostained ccRCC specimens, 91 (20.6%) and 107 (24.3%) showed negative-expression of PBRM1 and BAP1, respectively. Fifty-eight (13.2%) showed negative-expression of both markers (PBRM1-/BAP-). There was an association between both markers expression pattern and classical parameters, such as pT stage (P<0.001), tumor size (P<0.001), and tumor grade (P<0.001). Both independent PBRM1 and BAP1 negative-expression were associated with lower rates of disease-specific survival and recurrence-free survival. When patients were grouped into presence of positive expression of one or both markers vs. PBRM1-/BAP1- patients, disease-specific survival and rates were 95.3% vs. 77.6%, respectively (P<0.001). PBRM1-/BAP1-group presented a higher risk of cancer specific death (hazard ratio = 2.722, P = 0.007) and disease recurrence (hazard ratio = 2.467, P = 0.004) in multivariate analysis. CONCLUSION: Patients with early stage tumors that present concomitant loss of both PBRM1 and BAP1 demonstrated worse survival rates and represent a relevant risk group for tumor recurrence and death.

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group

Background: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. Objective: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥75 years of age. Methods: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (<75 vs.≥ 75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. Results: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p < 0.01) and higher ASA score (ASA >2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p < 0.01), EBL ≥ 500 cc (OR 3.34, p < 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. Conclusions: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities. (REV INVEST CLIN. 2020;72(5):308-15)