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Telomerase Activity in Soft-Tissue and Bone Sarcomas

Cellular and Molecular Biology, Hiroshima University School of Medicine, Hiroshima, Japan [K. A.]; Cranfield BioMedical Centre, Institute of Bioscience and Technology, Cranfield University, Bedfordshire MK43 0AL, United Kingdom [A. W.]; University of California San Diego Cancer Center and Department of Pathology, University of California San Diego, La Jolla, California 92093 [V. U., D. T., S. G.]; and Department of Musculoskeletal Pathology, Royal Orthopaedic Hospital, Birmingham B29 6AY, United Kingdom [D. C. M.]

The telomerase enzyme is a reverse transcriptase capable of replacing the telomeric DNA sequences that are lost at each cell division. Telomerase activation permits extended cell proliferation beyond normal senescence checkpoints, and accordingly, telomerase activity has been detected in a wide range of malignant cells and tissues but is absent in terminally differentiated somatic cells. To date, the majority of cancer-related telomerase analyses have been performed on carcinomas that originate from epithelial cells, and few reports have included tumors originating from nonepithelial cells. In this study, we used the PCR-based telomeric repeat amplification protocol (TRAP) to assay telomerase activity in nuclear protein extracts obtained from a range of malignant and benign connective tissue lesions. In total, 62 histologically diagnosed specimens were analyzed including 37 sarcomas, 7 benign mesenchymal tumors, 12 normal tissue samples, and 6 carcinoma metastases obtained from bone. Thirty (81%) of the 37 primary sarcoma samples contained telomerase activity, and four of the six carcinoma metastases were also positive. Conversely, telomerase activity was detectable in only one of seven benign lesions and in none of the 12 normal connective tissue controls. Tumors of connective tissue origin can sometimes be difficult to categorize and to evaluate microscopically with regard to clinical management. As is the case in carcinomas, the presence of telomerase activity appears to be indicative of malignancy in mesenchymal tumor biopsy material and therefore may be useful as an adjunct to the pathologist in the assessment of borderline cases.

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