Novel modalities for prostate cancer screening: mast cells as predictors of disease, disease aggressiveness and marks of disease disparity - SUMMARY
Prostate cancer (PCa) is the second most common cancer in men in the United States. The absolute number
of men with PCa is projected to increase as a result of the ageing baby boomer population. However, the lack
of reliable biomarkers for PCa screening has led to decreased early detection, particularly for African American
(AA) men who have the highest PCa morbidity, metastatic risk and mortality rates than any other racial or
ethnic group in the US. When cancer is suspected, patients must undergo multiple needle core biopsies
because of the multifocal nature of PCa. Nonetheless, up to 34% of biopsied men are told they are cancer-free
when they are not, because the biopsies missed the cancer foci. Hence, it is critical to better define the
cellular and molecular features indicative of PCa development and risk for aggressive disease in benign
biopsies of PCa patients to improve diagnosis and screening. In this grant, we are proposing to explore a
variation on the concept of field effect in PCa, postulating that histopathologically benign looking prostate core
biopsies may in fact feature alterations indicative of PCa and of PCa aggressiveness present in the same
patient at another prostatic site, using age- and race-matched (AA and Caucasian Americans (CA)) sets of
samples (benign and cancer-bearing biopsies for each patient). Prostate-resident mast cells (MC) aggregate in
stromal, peritumoral and/or intratumoral areas but their clinical relevance remains controversial. Our preliminary
data suggests the usefulness of establishing MC profiles in benign prostatic tissues of PCa patients. The
objectives of this application are: to investigate MC functional profiles in benign human prostate tissues as
predictors of PCa aggressiveness and candidate functional biomarkers of PCa race disparity; to define and
validate a molecular signature indicative of PCa and PCa aggressiveness present in benign human prostate
biopsies and test its predictive value for PCa disparity and association to MC; and apply our new screening
modalities in clinics, contingent upon successful validation studies. We anticipate that our approach may
improve diagnosis and screening for high-risk PCa and position MC as potential drivers of PCa disparity.
