Abstract 2727: Clinical significance of PTEN in UTUC

Abstract

Abstract Upper tract urothelial carcinoma (UTUC) is a rare malignancy accounts for about 5% of all urothelial tumours. The cancer cells start in the layer of tissue urothelium, and found in the renal pelvis, renal calyces or ureters. When compare the UTUC to the bladder urothelial carcinoma, the pathological and clinical findings are often look and act alike. Previous studies indicated that deletion of phosphatase and tensin homologue (PTEN) gene is common to be found in bladder cancer. As known tumor suppressor gene PTEN is located on chromosome ten and considered as an important negative regulator for the PIP3/Akt signaling pathway to promote cell proliferation and inhibit apoptosis. Thus, this study we aimed to determine clinical significance of PTEN in UTUC. We collected sixty-eight formalin-fixed paraffin-embedded (FFPE) UTUC samples, the tumor stage was according to American Joint Committee on Cancer (AJCC) with Ta (n=15), T1 (n=11), T2 (n=10), T3 (n=18), T4 (n=7) and seven patients with unknown; in which male no.32, female no.36; the median age is 68 y/o (range 40-85 y/o). Fluorescence in situ hybridization (FISH) was performed to exam the PTEN gene copy number or gene structure alterations of UTUC; besides, immunohistochemistry (IHC) analysis were used to observe the PTEN protein expression in the tumor. Our results showed PTEN mutations were observed in twenty-two tumors with heterozygous PTEN deletion; one tumor with homozygous PTEN deletion, and three tumors with PTEN monosomy. Further, heterozygous PTEN deletion was shown significantly associated with stage of pTa, pT1 and pT2 (P=0.048) and history of smoking (P=0.030). The IHC results showed lower expression level was common to be observed in the tumor area. Our findings suggest loss of PTEN is associated with the low-risk group of UTUC but not the high-risk group, the unknown mechanisms between these two subtypes might be existed. Besides, smoking could also as a factor highly emerge from genetic alterations in UTUC. In conclusion, PTEN genomic loss might act a predictive indicator of classification of UTUC, however, the clinical treatment could be different due to the underlying diversity of the molecular activities. Citation Format: Liang-Chen Li, Cheng-Keng Chuang, Hung-Ying Chiang, Ying-Tzu Chen, Po-Hung Lin, Kai-Jie Yu, See-Tong Pang, Wen Hui Weng*. Clinical significance of PTEN in UTUC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2727. doi:10.1158/1538-7445.AM2017-2727