[Carcinoma in situ of the testis: predisposition, evolution and early detection]

Abstract

Carcinoma in situ (CIS), also known as intratubular germ cell neoplasia unclassified, is the common obligate precursor lesion of malignant testicular seminomatous and non-seminomatous germ cell tumors (GCT), which show a steadily increasing incidence in Europe. Although GCT is a potentially curable cancer with excellent prognosis even in patients with organ metastasis, many patients suffer from chemotherapy-associated effects and some develop a secondary (non-germ cell) malignancy. Recently, genome-wide association studies revealed genetic predispositions linked to six genes (KITL, SPRY4, BAK1, TERT, ATF7IP, DMRT1). Exposure to environmental factors was also linked to increased prevalence of testicular dysgenesis and CIS/GCT by the action of hormone disruptors on embryonal gonadal tissue during pregnancy. By unknown mechanisms these genetic and environmental factors might create a disturbed microenvironment in the fetal testis leading to survival of embryonic germ cells and subsequent malignant transformation might result in CIS. Molecular pathways involved in this process include activated cKIT pathway and LIN28 associated deregulation of miRNA targets. The challenge for the future is to identify high risk patients prior to invasive GCT, to develop non-invasive tests for detection of CIS on seminal material and elucidate the precise role of the microenvironment in CIS initiation.