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Clonal expansion and HPV-induced immortalization are early molecular alterations in cervical carcinogenesis
Tjoung-Won Park1, Sabine Riethdorf, Gudrun Schulz
1Department of Obstetrics and Gynaecology, University of Bonn, Bonn 53105. park@uke.uni-hamburg.de
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.