The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

Abstract

Background: The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT).

Methods: Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients.

Results: High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression.

Conclusions: These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status.

Figure 1

Quantification of hTERT mRNA (■) in germ cell tumor samples by real-time RT PCR. Quantification of PBGD mRNA (x) served as a reference for relative quantification. The copy numbers of the starting template were calculated by comparing the relative fluorescence signals of samples to external hTERT mRNA standards. X axis: cycle number, Y axis: fluorescence emission; Tissue specimen with N_hTERT = 85,2 copies.

Figure 2

Quantification of hTERT mRNA (■) in germ cell tumor samples by real-time RT PCR. Quantification of PBGD mRNA (x) served as a reference for relative quantification. The copy numbers of the starting template were calculated by comparing the relative fluorescence signals of samples to external hTERT mRNA standards. X axis: cycle number, Y axis: fluorescence emission; tissue specimen with N_hTERT = 2,1 copies.