BAP1與PBRM1基因突變在亮細胞腎細胞癌病人的影響

戴盟哲¹、魏子鈞^1,2,3、張延驊^1,2,3、林登龍^1,2,3

台北榮民總醫院 泌尿部¹；國立陽明大學醫學院 泌尿學科²；書田泌尿科學研究中心³

The effect of BAP1 and PBRM1 mutation on outcomes in patients with clear cell renal cell carcinoma (ccRCC)

Meng-Che Tai¹, Tzu-Chun Wei^1,2,3, Yen-Hwa Chang^1,2,3, Alex T.L. Lin^1,2,3

Department of Urology, Taipei Veterans General Hospital, Taiwan¹; Department of Urology, National Yang-Ming University, Taipei, Taiwan²; School of Medicine and Shu-Tien Urological Institute³

Purpose:

Renal cell carcinoma (RCC) accounts for 80 to 85% of primary kidney cancer. Clear cell renal cell carcinoma (ccRCC) is the most common subtype and often with aggressive pattern. It is characterized by inactivation of the von Hippel Lindau (VHL) tumor suppressor gene, which is located on chromosome 3p25. Recently, large-scale sequencing studies have identified other frequently mutated genes, including PBRM1, BAP1 and SETD2, located on chromosome 3p21, nearby VHL. Mutation on these genes have been reported to be correlated with the behaviors of ccRCC. This study was aimed to examine the oncological outcomes in patients with different gene mutations.

Materials and Methods:

We collected patients with clear cell RCC who received nephrectomy (partial or radical) from February, 2002 to October, 2010. BAP1 and PBRM1 mutation were investigated by immunohistochemistry (IHC) stain. Demographic data, histopathological reports, mutation distribution, progression-free survival and overall survival were analyzed.

Results:

Totally 204 patients were included. There were 30 patients with IHC stain loss of BAP1, 51 patients of PBRM1 and 79 patients of both BAP1 and PBRM1. The distribution had no relationship with demographic data or histopathological reports. For T stage distribution, patients with different phenotypes had a trend of T1 (early stage) percentage, with the lowest in patients with mutations both in BAP1 and PBRM1 (39.2%, p=0.0012), followed by mutation in BAP1 only, PBRM1 only, and no mutations. However there was no significant difference in progression-free survival and overall survival among each phenotype of mutations in BAP1 and PBRM1 genes.

Conclusions:

In our study, there was no differences in overall or progression survival between BAP1 and/or PBRM1 mutation status in ccRCC. The mutation phenotype was the independent factor only for T1 stage distribution among all, with the lowest percentage in patients with mutations both in BAP1 and PBRM1.