Jinchao Chen

Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel–Lindau Disease Families

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome. A phenomenon known as genetic anticipation has been documented in some hereditary cancer syndromes, where it was proved to relate to telomere shortening. Because studies of this phenomenon in VHL disease have been relatively scarce, we investigated anticipation in 18 Chinese VHL disease families. We recruited 34 parent-child patient pairs (57 patients) from 18 families with VHL disease. Onset age was defined as the age when any symptom or sign of VHL disease first appeared. Anticipation of onset age was analyzed by paired t test and the other two special tests (HV and RY2). Relative telomere length of peripheral leukocytes was measured in 29 patients and 325 healthy controls. Onset age was younger in child than in parent in 31 of the 34 parent-child pairs. Patients in the first generation had older onset age with longer age-adjusted relative telomere length, and those in the next generation had younger onset age with shorter age-adjusted relative telomere length (P < 0.001) in the 10 parent-child pairs from eight families with VHL disease. In addition, relative telomere length was shorter in the 29 patients with VHL disease than in the normal controls (P = 0.003). The anticipation may relate to the shortening of telomere length in patients with VHL in successive generations. These findings indicate that anticipation is present in families with VHL disease and may be helpful for genetic counseling for families with VHL disease families and for further understanding the pathogenesis of VHL disease.

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.

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.

AB180. The relationship between fructose-1, 6-bisphosphatase and hypoxia related genes expression in clear cell renal cell carcinoma

Objective Fructose-1,6-bisphosphatase (FBP1) is often known as a rate-limiting enzyme in gluconeogenesis. Recently, its catalytic activity-independent function, repress hypoxia induced factor (HIF) in the nucleus, was identified. The aim of this study was to investigate the relationship between FBP1 and hypoxia related genes expression in clear cell renal cell carcinoma (ccRCC). Methods The expression levels of FBP1, HIF-1α, HIF-2α, erythropoietin (Epo) and carbonic anhydrase IX (CA9) were assessed by immunochemical staining in archival ccRCC paraffin blocks from 123 patients using the tissue microarray technique. The expression level of FBP1 was then correlated with clinicopathological factors and the expression levels of HIF-1α, HIF-2α, Epo and CA9. Results Clinicopathological factors including age, gender, TNM stage and Fuhrman grade were indifferent between the patients with low FBP1 expression and those with strong FBP1 expression in ccRCC. FBP1 expression level was positively correlated with the expression levels of HIF-1α (P=0.005) and Epo (P=0.010), but without correlation with the expression level of HIF-2α (P=0.123) and CA9 (P=0.513) in ccRCC tissues. Conclusions Our findings may be useful for recognizing the association between FBP1 and hypoxia related genes expression and understanding the mechanisms of ccRCC tumorigenesis.