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Kashofer, K; Regauer, S.
Analysis of full coding sequence of the TP53 gene in invasive vulvar cancers: Implications for therapy.
Gynecol Oncol. 2017; 146(2):314-318
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kashofer Karl
Regauer Sigrid
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Abstract:
This study evaluates the frequency and type of TP53 gene mutations and HPV status in 72 consecutively diagnosed primary invasive vulvar squamous cell carcinomas (SCC) during the past 5years. DNA of formalin-fixed and paraffin embedded tumour tissue was analysed for 32 HPV subtypes and the full coding sequence of the TP53 gene, and correlated with results of p53 immunohistochemistry. 13/72 (18%) cancers were HPV-induced squamous cell carcinomas, of which 1/13 (8%) carcinoma harboured a somatic TP53 mutation. Among the 59/72 (82%) HPV-negative cancers, 59/72 (82%) SCC were HPV-negative with wild-type gene in 14/59 (24%) SCC and somatic TP53 mutations in 45/59 (76%) SCC. 28/45 (62%) SCC carried one (n=20) or two (n=8) missense mutations. 11/45 (24%) carcinomas showed a single disruptive mutation (3× frame shift, 7× stop codon, 1× deletion), 3/45 SCC a splice site mutation. 3/45 (7%) carcinomas had 2 or 3 different mutations. 18 different "hot spot" mutations were observed in 22/45 cancers (49%; 5× R273, 3× R282; 2× each Y220, R278, R248). Immunohistochemical p53 over expression was identified in most SCC with missense mutations, but not in SCC with disruptive TP53 mutations or TP53 wild-type. 14/45 (31%) patients with TP53 mutated SCC died of disease within 12months (range 2-24months) versus 0/13 patients with HPV-induced carcinomas and 0/14 patients with HPV-negative, TP53 wild-type carcinomas. 80% of primary invasive vulvar SCC were HPV-negative carcinomas with a high frequency of disruptive mutations and "hot spot" TP53 gene mutations, which have been linked to chemo- and radioresistance. The death rate of patients with p53 mutated vulvar cancers was 31%. Immunohistochemical p53 over expression could not reliably identify SCC with TP53 gene mutation. Pharmacological therapies targeting mutant p53 will be promising strategies for personalized therapy in patients with TP53 mutated vulvar cancers. Copyright © 2017. Published by Elsevier Inc.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Aged, 80 and over -
Carcinoma, Squamous Cell - complications
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - virology
Female -
Genotype -
Humans -
Immunohistochemistry -
Middle Aged -
Mutation -
Papillomaviridae - genetics
Papillomavirus Infections - complications
Papillomavirus Infections - virology
Prognosis -
Sequence Analysis, DNA -
Tumor Suppressor Protein p53 - genetics
Vulvar Neoplasms - complications
Vulvar Neoplasms - genetics
Vulvar Neoplasms - virology

Find related publications in this database (Keywords)
Vulva carcinogenesis
HVP-negative vulvar cancers
Therapy of vulvar cancer
Chemo-and radioresistance
p53 gene mutations
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