Abstract 4660: HPRT as a biomarker for tumor classification and its variability of expression in breast cancer

Abstract

Abstract The purpose of this study is to investigate the differential expression of HRPT between various breast cancer tissues in comparison to healthy breast tissue in order to evaluate its potential use as a diagnostic tool. Breast cancer is the most common malignancy diagnosed in women and remains incurable in the metastatic setting requiring accurate and reliable tools for early diagnosis. We analyzed HPRT, a purine salvage pathway enzyme responsible for synthesizing 90% of the available GMP and IMP in cellular maintenance. Due to its critical role in maintaining necessary nucleotides for cell proliferation, we hypothesized an increase in the expression of HPRT in cancer. Tissues from 48 patients with breast carcinoma were stained using standard immunohistochemistry (IHC) techniques. We examined infiltrating ductal carcinoma, margin of carcinoma, hyperplasia, atypical hyperplasia, adenosis, collagen fibers tissues, and normal breast tissue in order to determine expression between various breast cancers. Briefly, tissues were treated with a polyclonal anti-HPRT antibody along with a GADPH positive control and a universal negative control. Tissues were incubated with an HRP-polymer conjugated antibody, and DAP substrate which reacts to antibody-antigen binding sites and results in a color change. Adenosis and hyperplasia are benign breast conditions and are early signs of breast carcinoma development. Hyperplasia tissues, which are in a state of rapid proliferation, showed significant upregulation of HPRT and adenosis tissues showed approximately 42% upregulation. This HPRT upregulation in pre-stage 1 tissues indicates that it may be used as a biomarker to detect early stages of breast cancer. Expression of HPRT was also found to be upregulated in 65% of infiltrating duct carcinoma showing high expression in active malignant areas. In marginal tissue located on the perimeter of primary tumors only 31% of tissues show upregulation of the protein. Because the levels of HPRT in marginal tissue is significantly lower than those found in primary tumors, HPRT may serve as a useful diagnostic tool when evaluating successful tumor removal. These data suggests HPRT as a useful diagnostic tool when identifying tissue with a high proliferation rate indicative of potential cancer development. Additionally, HPRT may also be used as a tool for pathologists to evaluate the success of tumor removal. Citation Format: Michelle H. Townsend, Abigail M. Felsted, Jacob Clarke, Richard A. Robison, Kim L. O'Neill. HPRT as a biomarker for tumor classification and its variability of expression in breast cancer [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 4660. doi:10.1158/1538-7445.AM2017-4660