Carcinoma in situ of the testis. Detection of malignant germ cells in seminal fluid by means of in situ hybridization

Testicular germ cell tumors can be prevented if the neoplasia is diagnosed at the stage of carcinoma in situ (CIS). Hyperdiploid DNA content is one of the markers of CIS germ cells. We developed a noninvasive procedure for detection of CIS of the testis by means of a nonradioactive in situ hybridization assay with a probe for chromosome 1. Seminal cytospin smears from 2 men with isolated CIS changes, from 6 men in whom CIS was combined with a tumor, and from 16 control men without evidence of testicular neoplasia were tested. Ejaculates from men with CIS contained on average 2.6% hyperdiploid cells, whereas the corresponding percentage in the smears from controls was 0.2 (P = 0.009). In a blind study we identified samples from both patients with isolated CIS changes and from 3 of the 6 men in whom CIS was accompanied by a tumor, based on the percentage of the hyperdiploid cells. No false-positive results were obtained. Thus this study confirmed findings of previous immunocytochemical and flow cytometric studies that indicated exfoliation of CIS germ cells into seminal fluid. For detection of aneuploid cells in semen, in situ hybridization may be a more sensitive technique than flow cytometry. Applied on seminal samples, in situ hybridization may become a valuable and fast tool for diagnosis of CIS and thereby for prevention of testicular cancer.