title: Role of TP53 mutations in vulvar carcinomas.
abstract: Human papillomavirus (HPV)-independent development of vulvar carcinomas is common and the disruption of the TP53 pathway seems to play a key role in these tumors. Overexpression of TP53 in precursor lesions (differentiated VIN) and associated invasive carcinomas is regarded as an important diagnostic feature of this subtype of vulvar cancer. To determine the relationship of TP53 mutation status with clinicopathologic parameters, HPV status, and patient outcome, 18 squamous cell carcinomas of the vulva with TP53 overexpression along with 21 immunohistochemically TP53-negative tumors were analyzed. TP53 mutations were found in 17 (43.6%) of vulvar cancers, 18 (46.2%) tumors were HPV associated, and 8 (20.5%) carcinomas showed no relation to HPV infection or TP53 mutations. The presence of TP53 mutations was significantly linked to TP53 overexpression (P=0.002) and negative HPV status (P=0.012). The specificity of TP53 protein overexpression for the occurrence of TP53 mutations was 68.2%, with a positive predictive value of 66.7%. The most frequent mutation types were C:G →T:A transitions (57.9%). This mutation pattern strongly indicates the important role of oxidative stress in vulvar carcinogenesis. There were no relationships between TP53 mutation status and tumor stage, grading, nodal status, depth of invasion, or patient prognosis. In summary, TP53 mutations play a crucial role in a substantial proportion of vulvar carcinomas and are probably associated to cellular oxidative stress in chronically degenerative diseases of the vulva, such as lichen sclerosus. These data support the potential utility of restoring TP53 function as a therapeutic alternative in vulvar cancer. Further studies are necessary to clarify the prognostic implications of TP53 mutations in vulvar carcinomas.
authors.affiliation: Institute of Pathology, Department of Gynaecology, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. mchoschz@uke.uni-hamburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Choschzick
authors.forename: Widianto
authors.initials: W
authors.lastname: Hantaredja
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.forename: Frederike
authors.initials: F
authors.lastname: Gieseking
authors.forename: Linn
authors.initials: L
authors.lastname: Wölber
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D009154:Mutation; D030361:Papillomavirus Infections / Q000150:complications; D011237:Predictive Value of Tests; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53