Testicular cancer from diagnosis to epigenetic factors

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 Perdonà, Michele Caraglia _ and Gaetano Facchini

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Oncotarget. 2017; 8:104654-104663. https://doi.org/10.18632/oncotarget.20992

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Mariarosaria Boccellino1,*, Daniela Vanacore1,3,*, Silvia Zappavigna1, Carla Cavaliere2, Sabrina Rossetti3,4, Carmine D’Aniello5, Paolo Chieffi6, Evzen Amler7,13, Carlo Buonerba8, Giuseppe Di Lorenzo8, Rossella Di Franco3,9, Alessandro Izzo10, Raffaele Piscitelli3, Gelsomina Iovane4, Paolo Muto9, Gerardo Botti11,12, Sisto Perdonà10, Michele Caraglia1 and Gaetano Facchini3,4

1Department of Biochemistry, Biophysics and General Pathology, University of Campania “L. Vanvitelli” Naples, Naples, Italy

2Medical Oncology Unit, ASL NA 3 SUD, Ospedali Riuniti Area Nolana, Nola, Italy

3Progetto ONCONET 2.0, Linea progettuale 14 per l’implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo, Regione Campania, Italy

4Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’-IRCCS, Naples, Italy

5Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli, Italy

6Department of Psychology, University of Campania “L. Vanvitelli” Naples, Naples, Italy

72nd Faculty of Medicine, Charles University, V Uvalu 84, Prague 5, Czech Republic

8Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy

9Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’–IRCCS, Napoli, Italy

10Division of Urology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’-IRCCS, Naples, Italy

11Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”- IRCCS, Naples, Italy

12Scientific Management, Istituto Nazionale Tumori ‘Fondazione G. Pascale’-IRCCS, Naples, Italy

13Faculty of Biomedical Engineering, UCEEB, CVUT, Zikova 4, Prague 6, Student Science, H.Podluzi, Prague, Czech Republic

*These authors contributed equally to this work

Correspondence to:

Michele Caraglia, email: [email protected]

Keywords: testicular cancer, germ cell neoplasia, seminoma, biomarkers, epigenetic factors

Received: July 28, 2017     Accepted: August 29, 2017     Published: September 18, 2017


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).

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