Filippo Martignano et al., GSTP1 Methylation and Protein Expression in Prostate Cancer: Diagnostic Implications. Disease Markers

Filippo Martignano^1,2, Giorgia Gurioli¹, Samanta Salvi¹, Daniele Calistri¹, Matteo Costantini³, Roberta Gunelli⁴, Ugo De Giorgi⁵, Flavia Foca⁶, and Valentina Casadio¹

¹Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy
²University of Florence, 50121 Florence, Italy
³Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
⁴Department of Urology, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
⁵Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy
⁶Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy

Abstract:

GSTP1 belongs to the GSTs family, a group of enzymes involved in detoxification of exogenous substances and it also plays an important role in cell cycle regulation. Its dysregulation correlates with a large variety of tumors, in particular with prostate cancer. We investigated GSTP1 methylation status with methylation specific PCR (MS-PCR) in prostate cancer (PCa) and in benign tissue of 56 prostatectomies. We also performed immunohistochemistry (IHC) so as to correlate gene methylation with gene silencing. GSTP1 appears methylated in PCa and not in healthy tissue; IHC confirmed that methylation leads to protein underexpression (p < 0.001). GSTP1 is highly expressed in basal cell layer and luminal cells in benign glands while in prostatic intraepithelial neoplasia (PIN) it stains only basal cell layer, whereas PCa glands are completely negative. We demonstrated that methylation leads to underexpression of GSTP1. The progressive loss of GSTP1 expression from healthy glands to PIN and to PCa glands underlines its involvement in early carcinogenesis.

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