Abstract 1241: A large prostate cancer tissue microarray showed significant downregulation of hZIP1 in African American as compared to Caucasian men

Abstract

Abstract Prostate cancer (PC) originates mainly in the peripheral zone, where the majority of zinc (Zn) accumulating cells are located. The underlying basis of our study focuses on the essential trace element Zn which is needed in relatively high amounts for reproductive processes. PC is significantly more common in African American men (AAM) as compared to European American Men (EAM). Currently, the reason for this racial disparity is not understood, but like similar diseases, may develop due to the interaction of diverse risk factors including age, race, genetics, socioeconomic and lifestyle choices, broadly defined to include geographical and nutritional factors. Previous studies we have investigated the accumulation of Zn within the prostate gland of AAM and EAM, which showed that AA lose zinc levels in the glandular epithelia at an earlier age and have a relatively lower accumulation of Zn within the gland. Here, we present analyses of the ethnicity tissue microarray (TMA) of 267 core biopsies from AA and EA men. We carried out in situ RP PCR for hZIP1, hZIP2, hZIP3 and hZIP4 in all the TMAs and discovered that hZIP1 gene expression was significantly down-regulated and correspondingly, the cellular level of Zn was also depleted in the same areas where the hZIP1 was down-regulated. These effects occur in early and late stages of malignant development in the peripheral zone. Most importantly, we provide the evidence for the first time in a large TMA core biopsies that AAs have down-regulated their hZIP1 at a relatively higher degree than the age-and Gleason score matched EAs and that may explain why AAs have twice as much incident rate of PC than EAs, by utilizing two in situ detection methods. The following are the summary of our data: 1) The relative degree of hZIP1 is differentially expressed in the prostate tissues between stroma versus glandular areas. 2) The hZIP1 is downregulated in the glandular malignant tissues of the prostate. 3) The hZIP1 is also downregulated in the stromal areas in the malignant glands. 4) The degree of expression downregulation is significantly (p<0.001) in AA as compared to EA. 5) Downregulation of hZIP1 is significantly (p<0.001) downregulated in the glandular epithelia of AAs as compared to EAs. 6) hZIP2 and hZIP3 are also downregulated in the adenocarcinoma of both EA and AA but there were no significant differences between the two ethnic group with regards to degrees of expressions of these two zinc transporters (p<0.31). 7) hZIP4 appears to be absent in the prostate glands. 8) Zinc accumulation is depleted in the glandular regions of adenocarcinoma of prostate as compared to normal tissues. With the current technology we are unable to determine the degrees of zinc depletion in EA Vs AA. These data lead to the likelihood that the lost expression in the adenocarcinomatous glands may be due to down-regulation of hZIP1 that occurs in the in situ environment of the peripheral zone. Citation Format: Andre' Kajdacsy-Balla, Omar Bagasra, Vicky Y. Marcias, Katy Rezaei. A large prostate cancer tissue microarray showed significant downregulation of hZIP1 in African American as compared to Caucasian men. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1241. doi:10.1158/1538-7445.AM2015-1241