Relationship between von Hipple-Lindau tumor suppressor gene mutations and the prognosis of Chinese sporadic clear cell renal cell carcinoma / 中华泌尿外科杂志

ABSTRACT

Objective To evaluate the relationship between von Hippel-Lindau (VHL) gene mutations and the prognosis of Chinese sporadic clear cell renal cell carcinoma (CCRCC). Methods VHL gene mutations were detected by polymerase chain reaction (PCR), direct DNA sequencing in 74 paired specimens of sporadic CCRCC and normal kidney. The mutation findings, pathologic fea-tures and prognostic characteristics were analyzed. Results Fifty-one patients (68.9%) were in clinical stage T1, 9 patients (12.2%) were in T2 and 14 patients (18.9%) were in T3. In the aspect of pathological grade, 15 patients (20.3%) were in G1, 50 patients (67.6%) were in G2 and 9 pa-tients (12.2%) were in G3. VHL gene mutations were detected in 40 of 74 cases (54.1%). There were no significant differences of VHL gene mutations in different pathological grade and clinical stage of CCRCC, P=0.915, P=0.237, respectively. All patients were followed up for 34 to 107 months (mean 71 months). Seven patients died of CCRCC. Another 11 patients developed CCRCC related me-tastasis. Five-year tumor-free survival was 78%. The incidence of death or metastasis of CCRCC in VHL gene mutation group (15.0%, 6/40) was significant lower than non-mutation group (35.3%,12/34), P=0.043. Logistic regression results showed that lower tumor pathological grade and stage, better patients' prognosis would be (P=0.016, P=0.024, respectively). However, VHL gene muta-tion was related with better prognosis (P=0.033). This association was stronger among patients with high grade tumors (G3, P=0.048). Conclusions There are frequent VHL gene mutations in spo-radic Chinese CCRCC. Tumors' pathological grade and clinical stage are the important parameters for prognosis. However, VHL mutations are strongly associated with better cancer specific survival for CCRCC patients. These associations are relatively stronger in patients with high grade tumors.