Immunohistochemistry for human telomerase reverse transcriptase catalytic subunit (hTERT): a study of 143 benign and malignant soft tissue and bone tumours. Only a small number of mesenchymal tumours have been previously evaluated for hTERT expression. We hypothesised that hTERT expression would be frequently present in sarcomas, but not in benign tumours.Sections from 143 bone/soft tissue tumours were immunostained for hTERT (44F12, 1:20; Novocastra) using steam heat-induced epitope retrieval and the Dako Envision system. Normal lymphocytes served as positive internal controls. Positive cases showed 'speckled' nuclear/nucleolar staining in >10% of cells, in accordance with previous studies. Fisher's exact test was used for statistical analysis. The result was checked against the G test and Chi-squared test with Yates correction, and was concordant.hTERT expression was seen in nine of 71 (13%) benign and 33 of 72 (46%) malignant tumours (p > or = 0.001). hTERT was positive in >50% of osteosarcomas, malignant peripheral nerve sheath tumours, liposarcomas, and angiosarcomas. All positive sarcomas were high grade (FNCLCC grade II or III). Among benign tumours, only schwannomas and chondromas were positive in >30% of cases. Positive normal tissues included lymphocytes, multinucleated histiocytes, keratinocytes, adnexal glands, hepatocytes and basal cells of respiratory mucosa.hTERT expression is significantly more common in sarcomas as compared with benign tumours. Restriction of hTERT expression to high grade lesions, and its absence in low grade sarcomas (including the well-differentiated component of dedifferentiated liposarcoma), suggests that telomerase activation is a late event in sarcoma progression. Importantly, however, hTERT can be expressed in some benign tumours, notably schwannoma and chondroma, and it is doubtful that hTERT expression alone will allow the discrimination of benign from malignant soft tissue/bone tumours. Importantly, hTERT expression is often only focal and its identification may require careful evaluation of an entire section, suggesting that this technique is best applied to whole sections, rather than tissue microarrays.