BACKGROUND: Monoclonality, a hallmark of most neoplasias, is found in high-grade squamous intraepithelial lesions (Hi-SIL) and some low-grade SILs (Lo-SIL). The transforming genes E6/E7 of HPV 16 have been shown to induce telomerase activity and immortalization. We investigated the role of immortalization in monoclonal and polyclonal SILs. MATERIALS AND METHODS: Telomerase RNA (hTR) and HPV 16 E6/E7 were investigated in 45 Lo-, 33 Hi-SILs and 11 cervical carcinomas (SCC) by RNA/RNA in situ hybridization. Clonality in this series has been described previously. RESULTS: Expression of hTR and viral oncogenes correlated significantly with the histological severity of the lesion (p <0.001). Intense focal up-regulation of hTR was found in 14 out of 22 monoclonal Hi-SILs, 4 out of 20 monoclonal Lo-SILs but only 1 out of 15 polyclonal Lo-SIL. HPV 16 E6/E7 expression was detected in 20 out of 22 monoclonal Hi-SILs but only in 5 out of 21 monoclonal Lo-SILs. CONCLUSION: Monoclonal expansion and immortalization are early alterations predominantly found in SCC and Hi-SILs, but also in a subset of Lo-SILs.
