Evidence for at least three alternative mechanisms targeting the p16INK4A/cyclin D/Rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus.

Autor: Ferreux E; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Lont AP, Horenblas S, Gallee MP, Raaphorst FM, von Knebel Doeberitz M, Meijer CJ, Snijders PJ
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2003 Sep; Vol. 201 (1), pp. 109-18.
DOI: 10.1002/path.1394
Abstrakt: A comprehensive analysis of 53 penile carcinomas was performed to determine which mechanisms might be involved in the disruption of the p16(INK4A)/cyclin D/Rb pathway. To that end, human papillomavirus (HPV) presence, p16(INK4A) expression and promoter methylation, and expression of the BMI-1 polycomb gene product were studied. Sixteen (30%) of the carcinomas were found to harbour high-risk HPV DNA, 15 of which contained HPV 16. HPV 16 E6/E7 oncogene transcripts were detected in 13 (87%) of the carcinomas that contained HPV 16. Strong immunostaining for p16(INK4A) was significantly more frequent in carcinomas that contained high-risk HPV DNA (p < 0.001) and amongst those with HPV 16 DNA, it was more frequent in lesions in which E6/E7 transcripts were detectable (p = 0.029). This supports an active role for HPV E7 in interfering with the p16(INK4A)/cyclin D/Rb pathway. Methylation of the p16(INK4A) promoter or overexpression of the BMI-1 polycomb gene product may provide alternative modes of interference with this pathway. These phenomena were mutually exclusive and found in the absence of HPV in 15% and 10% of the penile carcinomas, respectively. These data indicate that there are at least three plausible mechanisms by which the p16(INK4A)/cyclin D/Rb pathway can become disrupted during penile carcinogenesis.
(Copyright 2003 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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