p73 is over-expressed in vulval cancer principally as the Delta 2 isoform. |
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Authors: | J O'Nions L A Brooks A Sullivan A Bell B Dunne M Rozycka A Reddy J A Tidy D Evans P J Farrell A Evans M Gasco B Gusterson T Crook |
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Affiliation: | Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG . |
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Abstract: | p73 was studied in squamous cancers and precursor lesions of the vulva. Over-expression of p73 occurred commonly in both human papillomavirus (HPV)-positive and -negative squamous cell cancers (SCC) and high-grade premalignant lesions. Whereas expression in normal vulval epithelium was detected only in the basal and supra-basal layers, expression in neoplastic epithelium increased with grade of neoplasia, being maximal at both protein and RNA levels in SCC. p73 Delta 2 was the principal over-expressed isoform in the majority of cases of vulval SCC and often the sole form expressed in SCC. Over-expression of p73 was associated with expression of HPV-encoded E7 or with hypermethylation or mutation of p16(INK4a) in HPV-negative cases. There was a close correlation between expression of p73 and p14(ARF) in cancers with loss of p53 function. The frequent over-expression of p73 Delta 2 in neoplastic but not normal vulval epithelium, and its co-ordinate deregulation with other E2F-1 responsive genes suggests a role in the oncogenic process. |
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Keywords: | vulval cancer HPV p73 |
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