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Scheda a cura di Marco Chilosi , Mattia Barbareschi e Claudio Doglioni (GYM) p63 PATOLOGIA PROSTATICA
PATOLOGIA PROSTATICA
p63 come marcatore delle cellule basali. Analogamente alla citocheratina-5 (identificabile con anticorpi 34bE12 o specifici per CK5) p63 è un ottimo marcatore delle cellule basali della ghiandola prostatica e trova utile applicazione nella identificazione di alterazioni associate alla trasformazione neoplastica, in particolare per riconoscere piccoli foci di carcinoma su agobiopsie.
L'assenza di cellule basali si associa significativamente alle alterazioni microambientali indotte dalla trasformazione neoplastica (anche se non indica con certezza la insorgenza di carcinoma). La dimostrazione inequivoca di uno strato di cellule basali esclude invece la possibilità che la ghiandola sia neoplastica.
La caratteristica espressione nucleare del marcatore lo rende utilissimo per doppie colorazioni con marcatori citoplasmatici (quali la alpha-methylacyl-CoA racemase (AMACR)
Doppia colorazione p63-AMACR
Doppia colorazione CK5-AMACR
Am J Pathol 2000 Dec;157(6):1769-75 p63 is a prostate basal cell marker and is required for prostate development. Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M. Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. The p53 homologue p63 encodes for different isotypes able to either transactivate p53 reporter genes (TAp63) or act as p53-dominant-negatives (DeltaNp63). p63 is expressed in the basal cells of many epithelial organs and its germline inactivation in the mouse results in agenesis of organs such as skin appendages and the breast. Here, we show that prostate basal cells, but not secretory or neuroendocrine cells, express p63. In addition, prostate basal cells in culture predominantly express the DeltaNp63alpha isotype. In contrast, p63 protein is not detected in human prostate adenocarcinomas. Finally, and most importantly, p63(-/-) mice do not develop the prostate. These results indicate that p63 is required for prostate development and support the hypothesis that basal cells represent and/or include prostate stem cells. Furthermore, our results show that p63 immunohistochemistry may be a valuable tool in the differential diagnosis of benign versus malignant prostatic lesions.
Cancer Res 2002 Apr 15;62(8):2220-6 Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer. Luo J, Zha S, Gage WR, Dunn TA, Hicks JL, Bennett CJ, Ewing CM, Platz EA, Ferdinandusse S, Wanders RJ, Trent JM, Isaacs WB, De Marzo AM. Department of Pathology, Brady Urological Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA. Identification of genes that are dysregulated in association with prostate carcinogenesis can provide disease markers and clues relevant to disease etiology. Of particular interest as candidate markers of disease are those genes that are frequently overexpressed. In this study, we describe a gene, alpha-methylacyl-CoA racemase (AMACR), whose expression is consistently up-regulated in prostate cancer. Analysis of mRNA levels of AMACR revealed an average up-regulation of approximately 9 fold in clinical prostate cancer specimens compared with normal. Western blot and immunohistochemical analysis confirms the up-regulation at the protein level and localizes the enzyme predominantly to the peroxisomal compartment of prostate cancer cells. A detailed immunohistochemical analysis of samples from 168 primary prostate cancer cases using both standard slides and tissue microarrays demonstrates that both prostate carcinomas and the presumed precursor lesion (high-grade prostatic intraepithelial neoplasia) consistently scored significantly higher than matched normal prostate epithelium; 88% of the carcinomas had a staining score higher than the highest score observed for any sample of normal prostate epithelium. Both untreated metastases (n = 32 patients) and hormone refractory prostate cancers (n = 14 patients) were generally strongly positive for AMACR. To extend the utility of this marker for prostate cancer diagnosis, we combined staining for cytoplasmic AMACR with staining for the nuclear protein, p63, a basal cell marker in the prostate that is absent in prostate cancer. In a simple assay that can be useful for the diagnosis of prostate cancer on both biopsy and surgical specimens, combined staining for p63 and AMACR resulted in a staining pattern that greatly facilitated the identification of malignant prostate cells. The enzyme encoded by the AMACR gene plays a critical role in peroxisomal beta oxidation of branched chain fatty acid molecules. These observations could have important epidemiological and preventive implications for prostate cancer, as the main sources of branched chain fatty acids are dairy products and beef, the consumption of which has been associated with an increased risk for prostate cancer in multiple studies. On the basis of its consistency and magnitude of cancer cell-specific expression, we propose AMACR as an important new marker of prostate cancer and that its use in combination with p63 staining will form the basis for an improved staining method for the identification of prostate carcinomas. Furthermore, the absence of AMACR staining in the vast majority of normal tissues coupled with its enzymatic activity makes AMACR the ideal candidate for development of molecular probes for the noninvasive identification of prostate cancer by imaging modalities.
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