Testicular cancer from diagnosis to epigenetic factors

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).

Bilateral Testicular Plasmacytomas

“…[1,2,8] There are several histologic origins of testicular tumors such as germ cell tumors (accounting for 90-95%), sex cord-stromal tumors (approximately 5-10%), and secondary testicular tumors (accounting for <1%). [2] Of these, seminomatous germ cell tumors are the most common giving rise to approximately one-third of all germ cell testicular tumors. [5] The sex cordstromal tumors come in one of two types: Leydig cell and Sertoli cell tumors, both of which are typically benign.…”

“…Finally, secondary testicular tumors are defined as tumors that arise in a different organ and then spread to the testes, with lymphoma being the most common. [2] Rarely, the testis can be a site for other secondary tumors, such as a plasmacytoma (0.03-0.15% of all testicular tumors), which is a solitary mass of neoplastic monoclonal plasma …”

“…[1,2] At the time of diagnosis, the majority of testicular tumors are unilateral, with bilateral testicular tumors occurring only 1-2% of the time. [3] Bilateral testicular tumors can occur either metachronously (80-85%) or synchronously (15-20%).…”

Histopathological evaluation of testicular tumors in our clinic

“…Çevresel etkenler ve genetik en sık suçlanan etiyolojik faktörlerdir (4,7). Kriptoorşidizm, testiküler mikrolitiazis, pestisidler, östrojen, inguinal herni, düşük doğum ağırlığı, ikizlerde, annenin hamilelik sırasında içtiği sigara, obezite, peynirden zengin diyet gibi durumlarda görülme oranı daha yüksektir (4,5,7). Baba ya da erkek kardeşinde testis tümörü olanlarda görülme riski 4-6 kez daha fazladır (4).…”

An up-date on epigenetic and molecular markers in testicular germ cell tumors

“…CIS cells as PGCs and gonocytes, express transcription factors associated with embryonic stem cell pluripotency, such as POU5F1/OCT-3/4, NANOG, T1A-2, MYCL1, GDF3, LIN28-A, DPPA4, DPPA5, KIT and AP-2γ. Genome-wide gene expression profiling revealed specific embryonic stem cell-like features of testicular CIS (30)(31)(32). The epigenetic pattern of CIS is associated with an open and permissive chromatin structure based on expression pattern of genes and transcription factors.…”