Prostate Cancer SkewingTowards Neuroendocrine Phenotype in High Grade or High StageAndrogen-Responsive Primary Prostate Cancer Luca Puccetti a, * , Claudiu T. Supuran b , Pier P. Fasolo a , Enrico Conti a , Giancarlo Sebastiani a , Sergio Lacquaniti a , Roberto Mandras a , Maria G. Milazzo c , Natalia Dogliani c , Paolo De Giuli c , Giuseppe Fasolis a a Ospedale San Lazzaro, Divisione di Urologia, Via Pierino Belli 26, 12051 Alba, Cuneo, Italy b Universita ` degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy c Ospedale San Lazzaro, Divisione di Anatomia ed Istologia Patologica, Via Pierino Belli 26, 12051 Alba, Cuneo, Italy Accepted 11 March 2005 Available online 2 April 2005 Abstract Objective: The prognostic influence of neuroendocrine (NE) differentiation in prostate cancer patients is not yet properly established. In a series of primary hormone-naive prostate cancers from a patient population that underwent radical prostatectomy, we wanted to determine the relationship between NE phenotype expression and Gleason sum, disease stage, and serum PSA concentration. Methods: Chromogranin A (CgA) expression was scored and compared in 105 consecutive primary prostate cancers with their homologous preoperative tumor prostate biopsies. Results: High grade or high stage prostate cancers expressed a significantly higher CgA score than low grade or localized diseases (p < 0.005). Both the CgA score of the surgical specimens and the PSA level in the serum increased linearly (p = 0.001). In the samples of many corresponding tumor biopsies no significant CgA staining was found. Conclusion: NE differentiation in primary untreated prostate cancer is closely associated with the major prognostic parameters of survival. This association cannot be shown by evaluating the CgA staining in tumor biopsies. # 2005 Elsevier B.V. All rights reserved. Keywords: Neuroendocrine differentiation; Chromogranin A; High grade prostate cancer; High stage prostate cancer; Serum PSA; Prostatic biopsies 1. Introduction Prostate carcinoma is the most frequent malignancy in the elder male and is a major health problem in Western societies [1,2]. It notoriously displays various clinical behaviours, ranging from relatively indolent to aggressive metastatic disease. A better understanding of the basic biology of human prostate cancer will improve our ability to successfully prevent, diagnose and treat this tumor. In prostate cancer, NE cells produce and secrete several important molecules which may positively or negatively select the expansion of prostate cancer cell clones and eventually drive androgen independent tumour growth [3]. NE cells are present in both normal and cancerous prostate tissue. Tumor NE cells differ- entiate from totipotential prostate cancer cells. In normal prostate tissue, NE cells differentiate from basal cells or may even originate from the neural crest European Urology European Urology 48 (2005) 215–223 * Corresponding author. Tel. +39 0173 31 6436; Fax: +39 0173 31 6596. E-mail addresses: lpuccetti@asl18.it, lpuccetti@tim.it (L. Puccetti). 0302-2838/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2005.03.018