Testicular cancer from diagnosis to epigenetic factors

Testicular cancer (TC) is one of the most common neoplasms that occurs in male and includes germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Diagnosis of TC involves the evaluation of serum tumor markers alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, but clinically several types of immunohistochemical markers are more useful and more sensitive in GCT, but not in teratoma. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C) and LIN28. Gene expression in GCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TG-subtypes that reflect the normal developmental switch in primordial germ cells from an under- to normally methylated genome. The main purpose of this review is to illustrate the findings of recent investigations in the classification of male genital organs, the discoveries in the use of prognostic and diagnostic markers and the epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and microRNAs (miRNAs).

Oncotarget. 2017 Sep 18*** epublish ***

Mariarosaria Boccellino, Daniela Vanacore, Silvia Zappavigna, Carla Cavaliere, Sabrina Rossetti, Carmine D'Aniello, Paolo Chieffi, Evzen Amler, Carlo Buonerba, Giuseppe Di Lorenzo, Rossella Di Franco, Alessandro Izzo, Raffaele Piscitelli, Gelsomina Iovane, Paolo Muto, Gerardo Botti, Sisto PerdonĂ , Michele Caraglia, Gaetano Facchini

Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli" Naples, Naples, Italy., Medical Oncology Unit, ASL NA 3 SUD, Ospedali Riuniti Area Nolana, Nola, Italy., Progetto ONCONET 2.0, Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo, Regione Campania, Italy., Division of Medical Oncology, A.O.R.N. dei COLLI "Ospedali Monaldi-Cotugno-CTO", Napoli, Italy., Department of Psychology, University of Campania "L. Vanvitelli" Naples, Naples, Italy., 2nd Faculty of Medicine, Charles University, V Uvalu 84, Prague 5, Czech Republic., Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy., Division of Urology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS, Naples, Italy., Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS, Naples, Italy., Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale'-IRCCS, Napoli, Italy., Pathology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"- IRCCS, Naples, Italy.