Dysregulated p15 in urothelial carcinoma of the upper urinary tract
Resource
Cancer Res., 72,
Journal
Cancer Res.
Journal Issue
72
Pages
-
Date Issued
2012
Date
2012
Author(s)
Ho, Pei-Yin
Tsai, Yu-Chieh
Huang, Chao-Yuan
Chung, Shiu-Dong
Yang, Hsin-Yi
Peng, Hsiang-Chi
Lin, Ching-Hung
Lai, Ming-Kuen
Abstract
Abstract OBJECTIVE: To investigate tumorigenic characteristics of upper urinary tract urothelial carcinoma (UTUC) by evaluating genomic alterations and protein expression of p15, located in 9p21, in primary tumors and in the morphologically normal pelvis of UTUC patients. METHODS: 10 pairs of tumor and pelvis tissues were submitted for comparative genomic hybridization (CGH) to examine chromosome abberations. Western blotting assays were performed to compare the fold change of p15 expression between another 16 pairs of tumor and normal tissues. Immunohistochemistry was conducted to determine the presence of p15-positive tumor cells and staining intensity in 53 tumor tissues, including 26 superficial and 27 invasive tumors. The Student's t-test and Chi-square test were applied to explore the correlation between the p15 expression and clinicopathologic parameters of UTUC patients. RESULTS AND CONCLUSIONS: CGH revealed incomplete 9p21 in 70% of UTUC tumors, including 3 low-grade and 7 high-grade cases. Results of Western blotting assays showed high frequencies (75%) of p15 downregulation (fold change > 1.5) in UTUC tissues compared to their normal pelvis control. Immunohistochemistry results indicated that superficial tumors had lower p15 expression than invasive tumors (p=0.002). In patients with tumor metastases, local recurrence or distal recurrence, the p15 expression level was significantly increased in UTUC tissues (p=0.038, 0.01 and 0.017, respectively). Taken together, our data suggest that the decreased expression of p15 may be an important step in early neoplastic transformation of the urothelium of upper urinary tract and, during tumor progression, p15 may be up-regulated by other molecules, such as SP-1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4564. doi:1538-7445.AM2012-4564
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