Nienie Qi

Higher programmed cell death 1 ligand 1 (PD-L1) mRNA level in clear cell renal cell carcinomas is associated with a favorable outcome due to the active immune responses in tumor tissues

Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45.0 and 37.1 months respectively (p=0.002). Multivariate Cox regression tests found that PD-L1 mRNA level in tumor was an independent predictor for overall survival status in kidney clear cell cancer patients (HR=0.7, 95% CI 0.5-0.9, p=0.007). However, no significant difference in overall survival status was found between high and low PD-L1 groups in kidney papillary cell carcinoma and kidney chromophobe cohorts. Gene-set enrichment analysis on the data from databases of TCGA and GSE53757 dataset in Gene Expression Omnibus databases showed that several pathways relating to immunological functions were activated in kidney clear cell cancers with high PD-L1 mRNA expression, and glycolysis and epithelial-mesenchymal transition pathways relating to tumor progression and metastasis were increased in kidney clear cell cancers with low PD-L1 mRNA level. In conclusion, higher PD-L1 mRNA level in kidney clear cell cancer tissues was associated with a favorable outcome due to the higher immunological responses in tumor tissues.

Shorter telomere length increases age‐related tumor risks in von Hippel‐Lindau disease patients

Von Hippel‐Lindau (VHL) disease is a rare autosomal dominant cancer syndrome caused by alterations of VHL gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within VHL families. However, no reliable markers have been found to predict the age‐related tumor risks in VHL patients. A large Chinese cohort composed of 300 VHL patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic DNA samples. Age‐related risks for the five major VHL‐associated tumors were evaluated using Kaplan–Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. VHL patients showed significantly shorter telomere length than healthy family controls(P = 0.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age‐adjusted telomere length ≤ 0.44) suffered higher age‐related risks for VHL‐associated central nervous system hemangioblastomas (HR: 1.879, P = 0.004), renal cell carcinoma (HR: 2.126, P = 0.002) and pancreatic cyst and neuroendocrine tumors (HR: 2.093, P = 0.001). These results indicate that blood shorter telomere length is a new biomarker for age‐related tumor risks in VHL patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of VHL‐associated tumors.

Clinicopathologic Features and Prognosis of Sporadic Bilateral Renal Cell Carcinoma: A Series of 148 Cases

Micro‐Abstract Sporadic bilateral renal cell carcinoma (RCC) is relatively rare in RCC. Sporadic bilateral RCC is a distinct subtype and has different biological behaviors compared with hereditary bilateral RCC. The latter occurrence does not bear a significantly worse pathologic biology in metachronous bilateral RCC. The prognosis of patients with sporadic bilateral RCC is comparable with that of patients with unilateral RCC. Introduction: The purpose of this study was to investigate the clinicopathologic features, treatment, and prognosis of sporadic bilateral renal cell carcinoma (RCC). Patients and Methods: A total of 148 patients with sporadic bilateral RCC treated in our center from June 1986 to December 2015 were included in this retrospective study. Their clinicopathologic features and treatments were evaluated. The survival and prognostic factors were assessed based on data from follow‐up. Results: The median age was 54 years (range, 31‐78 years). There were 88 patients with synchronous bilateral RCC and 60 with metachronous bilateral RCC. The median interval between bilateral tumors of metachronous bilateral RCC was 75.5 months. There was no significant difference in tumor size, nuclear grade, or T stage between metachronous tumors (P = .385, P = .544, and P = .263, respectively). Of 148 patients, 124 patients underwent bilateral surgery, 16 underwent unilateral surgery, and 8 patients did not undergo surgery. Of the 317 tumors with pathologic results, 297 (93.7%) were clear‐cell subtype. A total of 136 (91.9%) patients were followed‐up, and the median follow‐up period was 77 months (range, 2‐398 months). During follow‐up, 38 (27.9%) patients died. The 5‐year overall survival rate was 85.9%. The median survival time of patients with no surgery was 5 months. Older age (P = .001), bilateral nonoperative treatment (P < .001), higher T stage (P < .001), and multifocality (P = .02) were related to worse prognosis in multivariate analysis. Conclusion: In metachronous bilateral RCC, the latter occurrence does not bear a significantly worse pathologic biology. The prognosis of sporadic bilateral RCC with no surgery is poor. The overall oncologic results of patients with sporadic bilateral RCC are comparable with that of patients with unilateral RCC.

Risk factors for survival in patients with von Hippel-Lindau disease

Background Historically, von Hippel-Lindau (VHL) disease is characterised by a poor survival. Although genotype–phenotype correlation has been described in many studies, the risk factors for VHL survival remain unclear. This study aims to evaluate the median survival of Chinese patients with VHL disease and explore whether VHL survival is influenced by genetic and clinical factors. Methods In this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan-Meier plot and Cox regression model were used to evaluate the median survival and assess how survival was influenced by birth year, birth order, sex, family history, mutation type, onset age and first presenting symptom. Results The estimated median life expectancy for Chinese patients with VHL disease was 62 years. Patients with early-onset age, positive family history and truncating mutation types had poorer overall and VHL-related survival. Patients with haemangioblastoma as their first presenting symptom were related to a higher risk of death from central nervous system haemangioblastoma than those with abdominal lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004). Conclusions This largest VHL survival analysis indicates that onset age, family history, mutation type and first presenting symptom have an effect on the survival of patients with VHL disease, which is helpful to genetic counselling and clinical decision-making.

Genotype and phenotype correlation in von Hippel–Lindau disease based on alteration of the HIF-α binding site in VHL protein

PurposeVon Hippel–Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype–phenotype correlation based on alterations in VHL protein (pVHL).MethodsVHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared.ResultsMissense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations.ConclusionThe modified genotype–phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies.

PD04-07 HIGHER PD-L1 MRNA LEVEL IN CLEAR CELL RENAL CELL CARCINOMAS IS ASSOCIATED WITH A FAVORABLE OUTCOME

INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in RCCs in predicting outcome of the patients is yet unclear. METHODS: We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer (KIRC), 259 kidney papillary cell carcinoma (KIRP) and 66 kidney chromophobe (KICH) patients from The Cancer Genome Atlas (TCGA) database. RESULTS: In KIRC patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45.0 and 37.1 months respectively (p1⁄40.002). Multivariate Cox regression tests found that PD-L1 mRNA level in tumor was an independent predictor for overall survival status in KIRC patients (HR1⁄40.7, 95% CI 0.5-0.9, p1⁄40.007). However, no significant difference in overall survival status was found between high and low PD-L1 groups in KIRP and KICH cohorts.Gene-set enrichment analysis on the data from databases of TCGA and GSE53757 dataset in GEO showed that several pathways relating to immunological functions were activated in KIRCs with high PD-L1 mRNA expression, and glycolysis and epithelial-mesenchymal transition pathways relating to tumor progression and metastasis were up-regulated in KIRCs with low PD-L1 mRNA level. CONCLUSIONS: In conclusion, higher PD-L1 mRNA level in KIRC tissues was associated with a favorable outcome due to the higher immunological responses in tumor tissues.

Renal Arterial Pseudoaneurysm and Renal Arteriovenous Fistula Following Partial Nephrectomy

Introduction: Renal arterial pseudoaneurysm (RAP) and renal arteriovenous fistula (RAVF) are rare but can cause fatal bleeding. Materials and Methods: A retrospective review was conducted for patients undergoing partial nephrectomy (PN) in our department. The clinical features and treatment methods were analysed, and the relationships between RAP/RAVF and the surgical methods and R.E.N.A.L. score were investigated. Results: Eleven patients were diagnosed with RAP/RAVF (9 with RAP and 2 with RAVF). The incidence of RAP/RAVF after laparoscopic PN showed no significant difference compared to that after open PN (p = 0.47). A low R.E.N.A.L. score was present in 6 patients, while an intermediate/high score was present in the other 5 patients. The major clinical manifestations included haematuria and haemorrhagic shock, and the median time of occurrence was 8 days after the operation. Six patients underwent an ultrasound examination. Of the 4 patients who underwent enhanced CT, 2 patients were diagnosed with RAP. All 11 patients were diagnosed by renal angiography and were cured after super-selective arterial embolization. The serum creatinine levels before and after embolization showed no significant differences (p = 0.14). Conclusions: RAP/RAVF may not have any relationship with the surgical procedure or R.E.N.A.L. score. Renal angiography and super-selective arterial embolization are the preferred methods for diagnosing and treating RAP/RAVF.

AB188. Single center experience of diagnosis, treatment and prognosis of specialized stromal tumors of the prostate

Objective Specialized stromal tumors of the prostate include stromal sarcoma and stromal tumors of uncertain malignant potential (STUMP). They are relatively rare and the clinical and prognostic features are unclear. Our study investigated diagnosis, treatment and prognosis of the disease. Methods We reviewed the clinical data of 13 patients diagnosed with specialized stromal tumors of the prostate from 2008 to 2015 in our department. A total of 12 patients were followed up, and we recorded the events of tumor recurrence, tumor progression, and cancer specific death. Results Patient age was 25 to 75 years (mean 50 years). The main clinical presentation included urinary obstructive symptoms (7/13), irritative symptoms (6/13), hematuria (5/13), rectal dysfunction (3/13) and prostate-specific antigen (PSA) elevation (2/13). Twelve patients underwent ultrasound examination which showed prostate neoplasm (n=3) and tumor beyond prostate (n=1). Eleven patients received pelvic MRI. Eight cases indicated prostate mass with enhancement, 1 case showed a mass outside prostate and 4 cases showed unclear boundaries with rectum. Of 8 patients taking prostate biopsy, 5 cases were diagnosed with STUMP, 1 case indicated stromal sarcoma and 1 case showed malignant tumor rising from prostatic stromal. Different treatments were used according to different conditions: 3 cases with pelvic exenteration, 3 cases with radical prostatectomy, 2 cases with radical prostatectomy after TURP, 2 cases with TURP, and 2 cases with prostate biopsy alone. Pathological diagnosis after surgery showed 4 cases of stromal sarcoma, 1 case of STUMP associated with sarcoma and 8 cases of STUMP. The median follow-up time was 32 months [2-55]. Among 
4 patients with stromal sarcoma, 1 patient died 3 months after surgery because of the disease, and the others survived for 
38-55 months without recurrence and metastasis. The patient with STUMP and sarcoma was alive with recurrence and metastasis 3 months after operation. Among 8 patients with STUMP, 1 patient suffered recurrence 5 months following operation and received pelvic exenteration with the pathology showing stromal sarcoma and died 7 months later. The others survived for 2-35 months, with 1 case recurring 16 months after radical prostatectomy, 1 case recurring 12 months and 23 months 
after each TURP respectively. There was no evidence of progression of disease for 2 cases of STUMP after biopsy. Conclusions Specialized stromal tumors of the prostate are clinically rare and have unspecific clinical manifestations. The diagnostic accuracy of biopsy is limited. The prognosis of stromal sarcoma is poor. The prognosis of STUMP is relatively well, but it still has the potential to recur or even become stromal sarcoma, which needs close follow-up.