[879] Does the Inverse Immunoexpression Pattern of Nestin and Androgen Receptor Predict Treatment Failure in Patients with Prostatic Adenocarcinoma?

J Jani, C Cohen, AO Osunkoya. Emory University School of Medicine, Atlanta, GA

Background: Prostate epithelial stem cells are primed by the urogenital mesenchyme to initiate bud formation and branching morphogenesis, ultimately culminating in glandular structures composed of luminal, basal and neuroendocrine cells. The true identity of these stem cells is however not yet fully understood. Androgens are critical to prostate organogenesis and play a major role in normal prostate function and the development of prostate cancer (PCa). The goal of this study is to correlate the expression of stem cell marker nestin with androgen receptor (AR) to potentially predict the treatment failure rate in cases of androgen independent tumors and the possibility of future targeted therapy.
Design: Sixty patients treated with radical prostatectomy between 1996 and 2007, for localized PCa, were studied. The patient population was divided into 4 quartiles of 15 cases each based on Gleason score (3+3=6, 3+4=7, 4+4 =8 and 4+5=9). A tissue microarray was constructed and immunohistochemical stains were performed for nestin and AR.
Results:

	Gleason score 3+3=6, 3+4=7 (30 cases)	Gleason score 4+4=8, 4+5=9 (30 cases)
Nestin +ve cases (%)	2 (7) 3+ diffuse	20 (67) 3+ diffuse
AR +ve cases (%)	30 (100) diffuse 3+	30 (100) focal 1+
+ve Lymph node metastasis (%)	0 (0)	9 (30)
+ve Angiolymphatic invasion (%)	0 (0)	9 (30)
+ve Extra Prostatic extension (%)	0 (0)	2 (7)
+ve Bone metastasis (%)	0 (0)	2 (7)

Membranous nestin expression was noted in tumor cells and adjacent small capillaries in 20/30 cases (67%) of high grade PCa while it was absent in 28/30 cases (93%) of lower grade PCa. In the 30/30 cases 100% of high grade PCa, AR stained focally with 1+ intensity staining while 30/30 cases 100% of lower grade PCa showed diffuse nuclear 3+ intensity staining.
Conclusions: This study further supports the theory of evolution of higher grade PCa from cancer stem cells. Nestin which was expressed in higher grade tumors in our series is required for colonizing distant metastatic sites and thus may be a potential marker of “metastasis initiating cancer stem cells” and treatment failure. It is therefore conceivable that the inverse expression patterns of nestin and AR intensity may predict treatment failure in patients with PCa.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 93, Wednesday Morning