Telomerase reverse transcriptase, hTERT,

Telomerase is a ribonucleoprotein polymerase which adds repeated telomeric DNA sequences, TTAGGG, to the ends of chromosomes. Telomerase activity is required for sustained cell division, being present in stem cells, germ cells, malignant cells and immortalised cell lines but not in normal somatic cells. Telomerase consists of a RNA moiety, human telomerase RNA component (hTERC), which acts as a template, and a protein moiety, the human telomerase reverse transcriptase, hTERT3. A third component, telomerase-associated protein (TEP1), is ubiquitous and does not correlate with levels of telomerase activity3. A number of previous biochemical studies have demonstrated telomerase in a range of malignant cells. The presence of hTERC can be demonstrated by Northern blot analysis or ins-situ hybridisation and is present predominantly in cancer cells3.

The presence of TERT can be demonstrated by immunohistochemistry on formalin-fixed, paraffin-embedded tissues. Staining is both nuclear and cytoplasmic. The cytoplasmic staining is thought to represent the nascent enzyme and can be demonstrated after most antigen retrieval methods. The demonstration of nuclear telomerase, the critical locus of action of the enzyme, has proven more difficult. A new enhancing buffer seems to reveal the otherwise masked telomerase within the nucleus4.

Immunohistochemical expression

Telomerase activty has been demonstrated in 85% of human cancers.

The study of only three cases of benign mesothelial proliferation is clearly inadequate, giving 95% confidence limits of 0-71%.

Increased telomerase activity is associated with poorer survival in colorectal carcinoma2.

In the lung, there is a progressive increase in hTERC and hTERT mRNA from low-grade atypical adenomatous hyperplasia to high-grade atypical adenomatous hyperplasia to non-mucinous bronchiolo-alveolar carcinoma3.

Diagnostic utility

• Possibly the differentiation of benign mesothelial proliferations from mesothelioma.

References

1 Kumaki, F., Kawai, T., Churg, A., Galateau-Salle, F. B., Hasleton, P., Henderson, D., Roggli, V., Travis, W. D., Cagle, P. T., Ferrans, V. J. Expression of Telomerase Reverse Transcriptase (TERT) in Malignant Mesotheliomas. Am J Surg Pathol 2002; 26:365-370

2 Wei, R. and Younes, M. Immunohistochemical detection of telomerase reverse transcriptase in colorectal adenocarcinoma and benign colonic mucosa. Hum Pathol 2002;33:693-6.

3 Nakanishi, K., Kawai, T., Kumaki, F., Hirot, S., Mukai, M. and Ikeda, E. Expression of human telomerase RNA component and telomerase reverse transcriptase mRNA in atypical adenomatous hyperplasia of the lung. Hum Pathol 2002;33:697-702.

4 Leung DT, Ma CH, Niu H, et al. Nuclear telomerase is less accessible to antibody probing than known nuclear antigens: retrieval with new immunostaining buffer. Histochem Cell Biol 2005; 123:105-12

This page last revised 4.11.2006.

©SMUHT/PW Bishop