My research has spanned both basic and translational aspects of prostate cancer.
Our laboratory has held grants since 2003 to study the importance of cell adhesion molecule CD44 in prostate cancer for several years. CD44 is alternately spliced, and the expression level together with which isoforms are expressed, differ between benign prostate cells and cancer cells. Moreover, RNA interference against the pro-growth, pro-invasive isoform of CD44, and re-expression of the tumor suppressor form, have shown promise in vitro and in vivo for reducing the malignant behavior of prostate cancer cells. In related studies, we have examined the role of microRNAs 373 and 520c in regulating CD44 in benign prostate and prostate cancer; studied how natural nutrients or medicinal substances such as silibinin and phenyl methylene hydantoins affect CD44; and elucidated the role of the MAP Kinase pathways (MEK, JNK, and p38), and the role of calcitonin and its receptor—functioning as a pro-growth paracrine hormone—in governing CD44 alternate splicing. Through extramural collaborations, I have helped study the role of macrophage migration inhibitory factor (MIF) and its receptor CD74 in bladder inflammation and interstitial cystitis. In another collaboration, I contributed to the understanding of matrix metalloprotease 26 in prostate cancer. Finally, I collaborated on studies of the significance of Mycoplasma hyorhinis and its p37 protein, which, like XMRV virus, is a candidate for an infectious promoter of prostate cancer. During these endeavors, I have trained college students doing summer research.
From 1997 to 2003, I produced a body of published work on the concept of atypical small acinar proliferation of the prostate (ASAP of the prostate). This is a continuum of histologic and cytologic findings on needle biopsy which are suspicious for but not diagnostic of, prostate cancer. The clinical significance of ASAP diagnosis and use of P504S immunostain to resolve ASAP, were studied. ASAP diagnosis has about a 45% predictive value for cancer on repeat biopsy in a number of studies. Other major projects included studies of immunostains for testicular cancer; the role of hTERT subunit of telomerase in prostate cancer and its suppression by androgen ablation therapy; the effect on the dual androgen receptor inhibitor dutasteride on histomorphology of treated prostates; and inflammatory pseudotumor and related spindle cell lesions of the bladder.
In 2003, I studied adenoid cystic-basal cell carcinoma (ACBCC) of the prostate, and found that this tumor, previously thought to be indolent, was aggressive. This has stimulated recent interest in the more common finding of cribriform, mucinous, glomeruloid, and other morphologies of prostate cancer that are more common than ACBCC, but are controversial as to their proper Gleason grading. Through outcome-based analysis of the importance of the several morphologic components of prostate cancer, we hope to identify more precisely the significance of these variations.