DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Tissue Microarray Assessment of Novel Prostate Cancer Biomarkers AMACR and EZH2 and Immunologic Response to Them in African-American and Caucasian Men

Principal Investigator: MEHRA, ROHIT
Institution Receiving Award: MICHIGAN, UNIVERSITY OF
Program: PCRP
Proposal Number: PC040517
Award Number: W81XWH-05-1-0173
Funding Mechanism: Health Disparity Training-Prostate Scholar Award
Partnering Awards:
Award Amount: $184,268.00


PUBLIC ABSTRACT

Prostate cancer is the second leading cause of cancer death for men in the United States. Unfortunately, among African-American men, the burden of this disease is even higher. At the same age, the presence of clinically significant prostate cancer in African-American men is approximately 50% higher than in white men. Furthermore, the death rate from prostate cancer is significantly higher in African-American men than Caucasian men. Various prior population studies have attempted to see if access to medical care, level of education, level of income, diet, smoking, alcohol intake and such sociologic factors may account for these differences, but this does not appear to be the case. The conclusion of these studies have led experts in the area to believe that the basic biology of prostate cancer in African-American men is very likely to be distinct than that in Caucasian men. However, no scientific findings to date have found the likely difference or a way to predict which African-American men are likely to progress rapidly to widely spread and lethal disease.

Various researchers, including those at our institution, have now reported two novel and clinically significant prostate cancer tissue biomarkers. These have been called alpha-methylacyl coenzyme A (AMACR) and the polycomb group protein enhancer of zeste homolog 2 (EZH2). Evidence exists that these markers predict who will have a more aggressive type of prostate cancer. Specifically, prostate cancers that are localized to the prostate gland but express high levels of the marker EZH2 are more likely to spread quickly outside the prostate gland, and these patients have been found to have worse outcomes such as quicker prostate cancer spread to bone or other organs and shorter times of survival. Also, AMACR is essential for optimal growth of prostate cancer cells. Both tumor markers may be involved as a potential cause for some prostate cancers to be more aggressive. Additionally, the latest report from our institution shows that AMACR protein is recognized by the body's immune system. Researchers were able to detect the presence of antibodies (one type of body's immune system response) specific to this protein from prostate cancer. Nobody to date has reported any differences among these markers in African-Americans or studied the amount of immune reaction to these proteins in African-American men. Such an analysis provides the opportunity to address potential biologic differences among African-American and Caucasian men with prostate cancer. Potential differences may lead to valuable insights into what underlies the more aggressive nature of prostate cancer in African-American men, as well as give doctors a very helpful tool to screen for and predict which patients are at risk for early progression when the cancer is at an earlier stage.

We hope to construct prostate cancer tissue arrays from African-American and matched Caucasian men in order to undertake this study. We will bank excess constructs for future studies of such nature. We will be studying two important questions: How much of the above tumor markers are present in cancers from African-American men when compared to Caucasian men. (2) If and how much of an immune reaction can be detected in the blood of African-Americans with prostate cancer.

There is a crucial need for information regarding biologic differences that may underlie the higher burden of disease borne among African-American men with prostate cancer. Uncovering these differences would most likely have far-reaching implications benefiting African-American patients, such as aid in earlier diagnosis via simple blood tests and helping doctors find out during an early stage of disease if the prostate cancer is likely to spread quickly in an individual African-American patient, and it may open doors to exploring new treatment options based on racially based biologic differences among prostate cancer patients. Our work will explore two very important and novel tumor markers and their immune response that may underlie these differences. As far as we know, no one to date has approached this question from a combination of two important scientific perspectives, namely tumor markers and immune reaction to them in prostate cancer among African-American men.