Role of the Renin-Angiotensin System Components in Renal Cell Carcinoma: A Literature Review.

PURPOSE OF REVIEW: The physiological aspects of renin-angiotensin system (RAS) components are described in this review. Additionally, we present the main results of studies that could indicate an association between alterations in these components and cancer, particularly renal cell carcinoma (RCC). RECENT FINDINGS: The RAS undergoes a series of homeostatic and modulatory processes that extend to hypertrophy, hyperplasia, fibrosis, and remodeling, as well as angiogenesis, pro-inflammatory responses, cell differentiation, stem cell programming, and hematopoiesis. The link between cancer-related inflammation and RAS signaling converge in the response to tumor hypoxia and oxidative stress mechanisms, particularly with the angiotensin type 1 receptor leading to activation of transcription factors such as nuclear factor κB (NF-κB), as well as members of the signal transducer and activation of transcription (STAT) family and HIF1⍺. Dysregulation of the physiological actions of RAS in the microenvironment of inflammation and angiogenesis promotes tumor cell growth.

Primary laparoscopic RPLND for pure seminona metastasis: feasibility of supine and lateral approaches.

INTRODUCTION: Retroperitoneal lymphadenectomy (RPLND) is well established as a primary treatment, especially for high-risk stage I and stage IIA/B nonseminomatous tumors, but its value in seminomatous tumors is underreported (1). Classically, seminomas with isolated retroperitoneal lymphadenopathy are treated with external beam radiation therapy or systemic chemotherapy. Although these modalities are effective, they are associated with significant long-term morbidity (2, 3). Some retrospective studies have demonstrated the potential of RPLND as a first-line treatment for stage IIa seminoma, and two very recent prospective trials, still with interim results: SEMS TRIAL and PRIMETEST(3-7). The RPLND robotic technique has been previously described in the post-chemotherapy scenario, however, surgical videos of primary laparoscopic approach are lacking, especially in seminomatous disease (8). MATERIALS AND METHODS: We present two cases of primary videolaparoscopic RPLND, using different approaches. Case 1: Thirty four years-old, with prior right orchiectomy for mixed tumor. After 8 months he presented an two cm enlarged interaortocaval lymph node. Percutaneous biopsy showed pure seminoma metastasis. Case 2: Thirty three years-old, with previous left orchiectomy for stage I pure seminoma, without risk factors. After nine months, the patient had a three cm enlarged para-aortic lymph node. RESULTS: The surgical time ranged from 150 to 210 minutes, with a maximum bleeding of 300 mL and hospital discharge in 48 hours. In one of the cases, we identified a significant desmoplastic reaction, with firm adhesions to the great vessels, requiring vascular sutures, however, no major complication occurred. Pathological anatomy confirmed pure seminoma lymph node metastases in both cases. CONCLUSION: Laparoscopic primary RPLND proved to be technically feasible, with less postoperative pain and early hospital discharge. We understand that more studies should be performed to confirm our oncological results.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer.

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

A comparative study of AJCC and the modified staging system in pT2/pT3 penile squamous cell carcinoma - a validation on an external data set.

AIMS: The recent changes in the American Joint Commission on Cancer, 8th edition (AJCC-8E) pT2 and pT3 tumour definitions for penile cancer need robust validation studies. A recent study redefined and modified the pT2 and pT3 stages incorporating the histopathological variables (tumour grade, lymphovascular invasion, perineural invasion) similar to that used in the current AJCC-8E pT1 stage tumour subclassification. In this study, we validate and compare this proposed staging with the AJCC staging systems on an external data set. METHODS AND RESULTS: The data set from a previously published study was obtained. pT2 and pT3 stages were reconstructed as per AJCC 7th edition (AJCC-7E), AJCC-8E and the proposed staging. The staging systems were correlated with nodal metastasis, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). All systems were compared using receiver operating characteristic (ROC) curves. A total of 281 cases formed the study cohort. AJCC-8E (P = 0.031) and the proposed staging (P = 0.003) correlated with nodal metastasis on adjusted analysis, the latter with a better strength of association (AJCC-8E, γ = -0.471; proposed, γ = -0.625). On adjusted analysis, all the staging systems had a significant correlation with DFS, while only AJCC-8E and the proposed staging correlated with CSS and OS. On ROC curve analysis, the proposed staging had the highest area under the curve and was the only staging system to statistically correlate with all the outcome variables. CONCLUSIONS: The proposed staging for pT2/pT3 tumour stages in penile cancer may improve the prognostic and predictive ability.

Informed consent and a risk-based approach to oncologic surgery in a cancer center during the COVID-19 pandemic.

BACKGROUND: Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). OBJECTIVES: To report an IC and an algorithm developed for oncologic surgery during the COVID-19 outbreak. METHODS: We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS-CoV-2 test and described all perioperative steps of this program. RESULTS: Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS-CoV-2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. CONCLUSIONS: During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.

Conservative vs radical bowel surgery for endometriosis: A systematic analysis of complications.

BACKGROUND: Endometriosis of the bowel can be associated with significant morbidity. Surgery to remove it carries risks. Options include conservative shaving or discoid resection and more radical segmental bowel resection. AIMS: To determine if more conservative shaving or discoid bowel resection is associated with fewer risks than more radical segmental resection. MATERIAL AND METHODS: This study is a systematic review. We considered eligible any cohort, observational or randomised controlled trial (RCT) study of at least ten women per arm comparing conservative vs radical bowel surgery for endometriosis. We divided complications into two groups, major and minor. One additional article was added due to its significance in answering our study question as well as the high quality of the study design as an RCT. RESULTS: There were 3041 studies screened. Eleven studies were included (n = 1648). For major complications, the risk ratio for shaving and disc excision vs segmental resection is 0.31 (95% CI 0.21-0.46), while the risk difference is -0.25 (95% CI -0.41 to 0.10). For minor complications, the risk ratio is 0.63 (95% CI 0.36-1.09), while the risk difference is -0.03 (95% CI -0.12 to 0.05). CONCLUSIONS: Conservative shaving or discoid excision surgery is associated with reduced complications. Previous studies demonstrated a trend toward this finding, but suffered from relatively low participant numbers, increasing the risk of type one statistical error. Our results allow surgeons to make informed choices about potential complications when deciding how to approach bowel endometriosis. The results also allow patients to have more information about the risks. However, outcomes in the studies analysed are heterogenous and are from low-quality evidence.

Small renal masses in Latin-American population: characteristics and prognostic factors for survival, recurrence and metastasis - a multi-institutional study from LARCG database.

BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.

Changes in lung ultrasound of symptomatic healthcare professionals with COVID-19 pneumonia and their association with clinical findings.

PURPOSE: To evaluate ultrasound signs of coronavirus disease-19 (COVID-19) pneumonia in symptomatic healthcare professionals and to correlate those changes with clinical findings. METHODS: All patients underwent real-time polymerase chain reaction (RT-PCR), lung ultrasound (LUS) and clinical evaluation on the same day. In each of the 12 areas evaluated in the LUS, the LUS signs were scored to generate the aeration score. RESULTS: A total of 409 participants had positive PCR, with a median age of 41 (35-51) years. All participants had clinical symptoms, with cough in 84.1%, fever in 69.7%, and dyspnea in 36.2% of cases. In the LUS, 72.6% of participants had B-lines >2, 36.2% had coalescent B-lines, and 8.06% had subpleural consolidations. The median aeration score was 3 (2-7). The aeration score differed significantly regarding the presence of cough (P = .002), fever (P = .001), and dyspnea (P < .0001). The finding of subpleural consolidations in the LUS showed significant differences between participants with or without dyspnea (P < .0001). CONCLUSIONS: In healthcare professionals with COVID-19, LUS plays a key role in the characterization of lung involvement. Although B-lines are the most common ultrasound sign, subpleural consolidations are those that most impact the respiratory condition.

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 (less than 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 less than 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 less than 0.01), EBL ≥ 500 cc (OR 3.34, p less than 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.

Long-term results of the implantation of the AMS 800 artificial sphincter for post-prostatectomy incontinence: a single-center experience.

OBJECTIVES: Report the long-term outcomes of the AMS 800 artificial sphincer (AS) for the treatment post-prostatectomy incontinence (PPI) in a single center in Brazil. MATERIALS AND METHODS: Clinical data from patients who underwent the procedure were retrieved from the medical records of individuals with more than 1 year of follow-up from May 2001 to January 2016. Continence status (number of pads that was used), complications (erosion or extrusion, urethral atrophy, and infection), malfunctions, and need for secondary implantation were evaluated. The relationship between complications and prior or subsequent radiation therapy (RT) was also examined. RESULTS: From May 2001 to January 2016, 121 consecutive patients underwent AS implantation for PPI at an oncological referral center in Brazil. At the last visit, the AS remained implanted in 106 patients (87.6%), who reported adequate continence status (maximum of 1 pad/day). Eight-two subjects (67.8%) claimed not to be using pads on a regular basis at the final visit (completely dry). Revision occurred in 24 patients (19.8%).Radiation therapy (RT) for prostate cancer following radical prostatectomy was used in 47 patients before or after AS placement. Twelve patients with a history of RT had urethral erosion compared with 3 men without RT (p=0.004). CONCLUSION: Considering our outcomes, we conclude that AS implantation yields satisfactory results for the treatment of PPI and should remain the standard procedure for these patients. Radiation therapy is a risk factor for complication.

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications.

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive disease that is associated with high rates of recurrence and death. Radical nephroureterectomy (RNU) with excision of the bladder cuff is considered the standard of care for high-risk UTUC, whereas kidney-sparing techniques can be indicated for select patients with low-risk disease. There is a significant lack of clinical and pathological prognostic factors for stratifying patients with regard to making treatment decisions. Incorporation of tissue-based molecular markers into prognostic tools could help accurately stratify patients for clinical decision-making in this heterogeneous disease. Although the number of studies on tissue-based markers in UTUC has risen dramatically in the past several years-many of which are based on single centers and small cohorts, with a low level of evidence-many discrepancies remain between their results. Nevertheless, certain biomarkers are promising tools, necessitating prospective multi-institution studies to validate their function.

Urological cancer related to familial syndromes.

Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC), succinate dehydrogenase kidney cancer (SDH-RCC), and more recently BAP1 germline mutation related RCC. Among tumors from the bladder or renal pelvis, some studies had reinforced the role of germline mutations in mismatch repair (MMR) genes, especially in young patients. In prostate adenocarcinoma, besides mutations in BRCA1 and BRCA2 genes that are known to increase the incidence of high-risk cancer in young patients, new studies have shown mutation in other gene such as HOXB13 and also polymorphisms in MYC, MSMB, KLK2 and KLK3 that can be related to hereditary prostate cancer. Finally, tumors from testis that showed an increased in 8 - 10-fold in siblings and 4 - 6-fold in sons of germ cell tumors (TGCT) patients, have been related to alteration in X chromosome. Also genome wide association studies GWAS pointed new genes that can also be related to increase of this susceptibility.

Predictive role of Trimprob associated with multiparametric MRI in the diagnosis of prostate cancer.

OBJECTIVES: To evaluate the predictive value of TRIMprob test to detect prostate cancer (PCa) in patients referred to prostate biopsy (PB). MATERIAL AND METHODS: Patients with PSA <10ng/mL and rectal exam without findings suggestive of prostate cancer were selected for TRIMprob evaluation. Exam was performed by a single operator through transperineal approach. Patients admitted for the study were submitted to TRIMprob and multiparametric magnetic resonance (mpMRI) and posteriorly to PB. RESULTS: In total, 77 patients were included. TRIMprob showed evidences of PCa in 25 (32.5%) and was negative in 52 patients (67.5%). The rate of detection of prostate cancer at biopsy was higher in patients with positive TRIMprob (16/25; 64.0%) than in patients with negative TRIMprob (11/52; 21.1%; p<0.001). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of TRIMprob were respectively 61.5%, 82.0%, 64.0%, 80.3% and 74.0%. ROC curve showed the following areas under the curve values for TRIMprob, mpMRI and combination of TRIMprob + mpMRI: 0.706; 0.662 and 0.741 respectively. At combined analysis, when both TRIMprob and mpMRI were negative for prostate cancer, accuracy was 96.3% or only 1 in 27 PB was positive (3.7%). CONCLUSIONS: Trimprob had similar predictive value for PCa in patients submitted to PB as mpMRI. Combined TRIMprob and mpMRI showed higher accuracy than when performed singly.

Tumor histologic grade is the most important prognostic factor in patients with penile cancer and clinically negative lymph nodes not submitted to regional lymphadenectomy.

INTRODUCTION: The presence and extension of inguinal lymph node metastasis are the main prognostic factors in patients with penile cancer. Physical exam and image exams are not adequate to evaluate inguinal lymph nodes and many patients are submitted to non-therapeutic lymphadenectomies. However, it is known that not all patients with clinically or histologically negative inguinal lymph nodes evolve favorably. CASUISTIC AND METHODS: the authors evaluated the clinical and pathologic characteristics of 163 patients with penile carcinoma and clinically negative inguinal lymph nodes followed for three or more years and their impact on global survival (GS) and cancer-specific survival (CSS) in the 10-year follow-up. Primary pathologic tumor stage (p=0.025) and the presence of high grade of tumor differentiation (p=0.018) were predictive of CSS. The presence of high grade tumor was an independent specific prognostic factor of death risk (RR 14.08; p=0.019). CONCLUSION: high histologic grade was an independent predictive factor of specific death risk in patients with penile carcinoma and clinically negative lymph nodes followed for three or more years.

Pattern of invasion is the most important prognostic factor in patients with penile cancer submitted to lymph node dissection and pathological absence of lymph node metastasis.

OBJECTIVES: To identify prognostic factors in a cohort of patients with penile carcinoma with pathological absence of lymph node metastasis (pN0), as penile carcinoma is a rare neoplasm in European countries, in which the presence of lymph node metastasis is the most important prognostic factor but few studies have examined patients with penile carcinoma with histologically negative nodes (pN0). PATIENTS AND METHODS: Of patients with penile carcinoma, 101 met the inclusion criteria; 47 (46.5%) underwent bilateral inguinal lymph node dissection (LND) and 54 (53.5%) underwent bilateral inguinopelvic LND. Variables that had a prognostic impact on survival rates in univariate analysis were selected for multivariate survival analysis. RESULTS: The cohorts cancer-specific survival (CSS) and overall survival (OS) rates were 88.1% and 52.5%, respectively. Histological grade and pattern of invasion were the only features to significantly impact survival rates in the univariate analysis. The CSS and OS rates in patients with 'pushing' vs 'infiltrating' patterns of invasion were 98.0% vs 78.4% (P = 0.003) and 70.0% vs 35.3% (P = 0.005), respectively. Pattern of invasion was the only independent predictor of survival. Patients with infiltrating invasion had a higher probability of death from cancer (hazard ratio [HR] 11.5, P = 0.019) and overall death (HR 2.3, P = 0.007) compared with those with a pushing invasion pattern. CONCLUSIONS: The presence of an infiltrating pattern of invasion is the most important predictor of survival in patients with penile carcinoma. We encourage other centres to confirm our findings that the pattern of invasion is an important prognostic factor in patients with penile carcinoma and pN0 disease.

SOD2 immunoexpression predicts lymph node metastasis in penile cancer.

BACKGROUND: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown. METHODS: SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis. RESULTS: SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis. CONCLUSIONS: Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.

Prognostic factors in patients with penile carcinoma and inguinal lymph node metastasis.

OBJECTIVES: To identify prognostic factors in patients with penile carcinoma and confirmed lymph node metastasis. METHODS: Patients were selected from a historical series of patients with penile carcinoma. An experienced pathologist reviewed all cases. Information regarding the total number of lymph nodes excised, the number of positive lymph nodes and the presence of extranodal extension were used. Lymph node ratio was categorized as <0.15 and >0.15. RESULTS: The 5-year recurrence-free survival and disease-specific survival rates were 55.3% and 64.1%, respectively. Lymphovascular invasion, lymph node ratio and pN status influenced survival rates in univariate analysis. Lymphovascular invasion and lymph node ratio remained as independent predictors of disease-specific survival and recurrence-free survival in the multivariate analysis. A risk stratification of death and tumor recurrence was observed when patients were grouped into three categories: absence of risk factors; the presence of one risk factor; and the presence of two or more risk factors. CONCLUSIONS: The presence of one or more of the following parameters is correlated with a significantly higher risk of death and tumor recurrence in patients with penile carcinoma and inguinal lymph node metastasis: extranodal extension, lymph node ratio >0.15 and lymphovascular invasion.

Polybromo-1 (PBRM1), a SWI/SNF complex subunit is a prognostic marker in clear cell renal cell carcinoma.

OBJECTIVE: To analyse the immunohistochemical and mRNA expression of SWI/SNF (SWItch/Sucrose NonFermentable) complex subunit polybromo-1 (PBRM1) in clear cell renal cell carcinoma (ccRCC) and its impact on clinical outcomes. PATIENTS AND METHODS: In all, 213 consecutive patients treated surgically for renal cell carcinoma (RCC) between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determined the most representative tumour areas for construction of a tissue microarray. In addition, mRNA expression of PBRM1 was analysed by reverse transcriptase-polymerase chain reaction. RESULTS: Of the 112-immunostained ccRCC specimens, 34 (30.4%) were PBRM1-negative, and 78 (69.6%) were PBRM1-positive. The protein expression of PBRM1 was associated with tumour stage (P < 0.001), clinical stage (P < 0.001), pN stage (P = 0.035) and tumour size (P = 0.002). PBRM1 mRNA expression was associated with clinical stage (P = 0.023), perinephric fat invasion (P = 0.008) and lymphovascular invasion (P = 0.042). PBRM1 significantly influenced tumour recurrence and tumour-related death. Disease-specific survival rates for patients whose specimens showed positive- and negative-PBRM1 expression were 89.7% and 70.6%, respectively (P = 0.017). Recurrence-free survival rates in patients with positive- and negative-expression of PBRM1 were 87.3% and 66.7%, respectively (P = 0.048). CONCLUSIONS: PBRM1-negative expression is a markedly poor prognosis event in ccRCC. We encourage PBRM1 study by other groups in order to validate our findings and confirm its possible role as a useful marker in the management of patients with ccRCC.