Abstract 4: Nuclear MTA1 overexpression is associated with aggressive prostate cancer and metastasis in African American men.

Abstract

Abstract Metastasis-associate protein 1 (MTA1) plays essential role in prostate cancer (PCa) progression and metastasis. We hypothesized that nuclear MTA1 overexpression in primary tumor tissues may provide meaningful information on prediction of poor prognosis, i.e. MTA1 may serve as a prognostic biomarker for aggressive PCa and a predictor of recurrent disease and metastasis. We used tissue microarrays and clinicopathological information of 301 patients (146 Caucasian Americans and 155 African Americans) who underwent prostatectomy in University of Mississippi Medical Center, Jackson, MS and in University of Iowa, Iowa City, IA. We evaluated MTA1 expression by immunohistochemistry with the emphasis on subcellular localization and total staining score, which accounted intensity and frequency. MTA1 was detected in both cytoplasm and nucleus, however exhibited different expression patterns in terms of subcellular localization depending on pathological category of PCa and metastasis. A significant statistical correlation (p=0.063) was observed between MTA1 nuclear staining and localized PCa compared to PIN, reaching more significance with the worst grade (Gleason >7) and metastatic lesions (p<0.006). When analyzed in terms of racial differences, the difference in MTA1 nuclear overexpression between patients with localized PCa was highly significant (p<0.001), with Caucasian Americans showing higher levels of MTA1. However, when stratified by Gleason score, there were substantial differences in MTA1 levels in low grade tumors (Gleason ≤ 7) compared to high grade tumors (Gleason>7) in African Americans and not in Caucasians, indicating that MTA1 may serve as an “ethnic” biomarker for aggressive disease in African Americans. Moreover, there was a tendency for higher MTA1 nuclear staining in recurrent compared to non-recurrent group (n=50), particularly in African Americans (2.3 times difference). In summary, our observation might have clinical relevance in discriminating subset of low grade Gleason≤7 African American patients with low MTA1 expression who will remain recurrent-free from the same subset that have high MTA1 levels indicating possibility to develop more aggressive disease and metastasis. Putting together results of the current study and our previous finding that MTA1 is downregulated by dietary stilbenes we emphasize new perspectives for PCa management in African American men. Citation Format: Steven J. Dias, Xinchaun Zhou, Marina Ivanovic, Michael P. Gailey, Swati Dhar, Zhi He, Alan Penman, Anait S. Levenson. Nuclear MTA1 overexpression is associated with aggressive prostate cancer and metastasis in African American men. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4. doi:10.1158/1538-7445.AM2013-4