Clonal expansion and HPV-induced immortalization are early molecular alterations in cervical carcinogenesis.

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.