Immunohistochemical Detection of Telomerase (hTERT) Protein in Human Cancer Tissues and a Subset of Cells in Normal Tissues

Abstract

We examined human telomerase reverse transcriptase (hTERT) protein distribution by immunohistochemistry in cultured cells and tissue sections. Cells with telomerase activity had nuclear positive signals whereas cells without telomerase activity did not. In most normal epithelial tissues, hTERT expression was prominent in the early proliferative descendent progenitors cells. In cancers with high telomerase activity, hTERT expression was detected in almost all neoplastic cells and correlated with telomerase activity levels, whereas cancers with low telomerase activity had fewer hTERT-positive cancer cells. In pediatric neuroblastomas with a favorable outcome, both the percentage of positive cells and the signal intensities of each hTERT-expressing cell decreased. These studies indicate that detection of telomerase at the cellular level is achievable and may have utility in cancer diagnostics.

Selective ablation of human cancer cells by telomerase-specific adenoviral suicide gene therapy vectors expressing bacterial nitroreductase

“…While a minority of tumour cells, such as the 5637 bladder carcinoma line and the UVW malignant glioma line, may display low hTR and hTERT promoter activity, from previous expression studies it is clear that a number of tumour types are good candidates for telomerasedirected therapies (Soder et al, 1997(Soder et al, , 1998Sarvesvaran et al, 1999;Wisman et al, 2000;Downey et al, 2001;Hiyama et al, 2001). Importantly, this situation is also expected to apply to the majority of normal adult somatic cells in vivo, suggesting that Ad-hTR-NTR and Ad-hTERT-NTR/CB1954 will be selectively toxic to cancer cells.…”

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

“…28 The recent development of antibodies directed against hTERT, applicable to formalin-fixed, paraffin-embedded sections is very promising in identifying precisely which cells within a given tumor express hTERT. 29,30 Telomeric repeat lengths (TRF lengths) were measured in 2 different samples of all 37 STSs and an attempt was made to correlate TRF lengths with TA, hTERT mRNA expression, tumor histology, grade and proliferative activity. In every case, tumor TRF lengths were compared to normal striated muscle TRFs from 10 tumor-free patients, of which the mean size was 12 kbp.…”

Clinical utility of telomerase in cancer

“…In specimens of adult cancers, the signal intensity in each hTERT positive cell did not di er substantially between tumors with high and low telomerase activity. The levels of telomerase activity in tumor tissues mainly depended on the ratio of telomerase positive to telomerase negative tumor cells (Hiyama et al, 2001). For cell or core biopsy samples, hTERT is detectable in para n-embedded section ( Figure 1) indicating that hTERT detection is a promising marker for cancer detection.…”

“…Thus, detections of both hTR expression by Northern blot analysis and hTERT mRNA expression by RT ± PCR analysis are also useful for evaluation. Moreover, hTR in situ hybridization or hTERT immunohistochemistry are also applicable for evaluation as surrogate markers of telomerase expression at the cellular level and in archival para n embedded specimens (Hiyama et al, 2001). The advantages and disadvantages of targeting hTR and hTERT expressions in cancer diagnosis are summarized in Table 1.…”