Testicular cancer from diagnosis to epigenetic factors.

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

doi:10.18632/oncotarget.20992

Abstract

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).

Highlights

Testicular cancer (TC) is the most common neoplasia that occurs in males between 20–40 years old and it accounts for approximately 1–1.5% of all cancers in men [1,2]
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
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

Summary

Introduction

Testicular cancer (TC) is the most common neoplasia that occurs in males between 20–40 years old and it accounts for approximately 1–1.5% of all cancers in men [1,2]. TC develops in testicles and includes several types of cancer, such as germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Among the risk factors correlated to the onset of disease we can remember: age, cryptorchidism, family history of TC, Klinefelter’s syndrome, personal history of TC, congenital abnormalities and infertility [11,12]. Age represents one of the most frequent factors of TC occurrence; the highest incidence of GCT has been found in men between 15 and 35 years old [13]. Surgical methods have been developed during the years and they represent the best treatment options to treat different types of TC varying depending upon the type and stage of cancer after diagnosis. Sometimes more than one type of treatment might be used including chemotherapy and/or radiotherapy [18]

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Conclusion