title: Cell cycle suppressor proteins are not related to HPV status or clinical outcome in patients with vulvar carcinoma.
abstract: Interactions between the cyclin-dependent kinase inhibitors (CDKI) and human papillomavirus (HPV) infection in the pathogenesis of vulvar carcinoma are still incomplete. This study aimed to evaluate the prognostic relevance of these proteins in vulvar cancer. One hundred and thirty-nine patient specimens assembled in a tissue microarray were evaluated for p16, p21, p27, and pRb by immunohistochemistry. HPV status was assessed by a linear array HPV genotyping test. In 16 cases with available frozen tumor, quantitative real-time reverse transcriptase-polymerase chain reaction for CDKN2A(p16), CDKN1A, and Rb was performed. Protein expression was considered positive in 40 patients for p16, 35 for p21, 28 for p27, and 19 for pRb. HPV was positive in 43 of the 105 evaluable cases. Expression of CDKIs and pRb, with the exception of p16, seem to be linked to the early phases of vulvar carcinogenesis. Although p16 and p21 protein expression was associated with early stages of disease, no prognostic significance was found when analyzing CDKI proteins or detecting HPV status, limiting their clinical usage. No association was observed between expression of CDKI proteins and HPV status, suggesting that in spite of this association found in cervical cancer, this seems not to be valid for vulvar carcinoma.
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Hospital, São Paulo, Brazil, lavorato.andre@gmail.com.
authors.forename: André Mourão
authors.initials: AM
authors.lastname: Lavorato-Rocha
authors.forename: Iara Sant'ana
authors.initials: IS
authors.lastname: Rodrigues
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Melo Maia
authors.forename: Mônica Maria Ágata
authors.initials: MM
authors.lastname: Stiepcich
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
authors.forename: Kátia Cândido
authors.initials: KC
authors.lastname: Carvalho
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005260:Female; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism* / Q000821:virology; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014846:Vulvar Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27