title: Prognostic value of p16(INK4a) as a marker of clinical evolution in patients with cervical intraepithelial neoplasia grade 3 (CIN 3) treated by cervical conization.
abstract: The aim of this study was to assess the prognostic value of p16(INK4a) as a marker of post-conization relapse in patients treated for cervical intraepithelial neoplasia grade 3 (CIN 3). A retrospective study of 76 women with CIN 3 diagnoses, treated at the Hospital of Santa Casa de Misericórdia of São Paulo (Brazil) between January 2003 and September 2004, was performed. The study samples were obtained from cervical conization procedures, where paraffin blocks containing areas with the greatest amount of neoplastic tissue were selected. Immunohistochemical techniques were used on individual paraffin blocks for each case to detect p16(INK4a) protein expression. The p16(INK4a) cell counts were performed in 10 different high-amplification fields (400x) by light microscopy and total cell count expressed as number of cells per mm(2) . Patients involved in this study were followed up at the colposcopy outpatient unit for at least 48 months after cervical conization. The correlation of p16(INK4a) values with post-conization evolution in the patients (disease relapse or disease free) was determined. A significantly higher count of cells expressing p16(INK4a) was found in those patients with disease relapse during follow-up (p < 0.001). The variables age, number of gestations, and births correlated positively with number of cells expressing p16(INK4a) cells (p < 0.001; p = 0.001; 0.009, respectively). No correlation was found for the variables menopause, hormonal contraception, or smoking (p = 0.369, 0.425 and 0.853, respectively). p16(INK4a) can be considered a biomarker of cervical intraepithelial neoplasia grade 3 cases presenting high risk of relapse or evolution to invasive carcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine of Santa Casa de São Paulo, São Paulo.
authors.forename: Fernanda Araujo
authors.initials: FA
authors.lastname: Cardoso
authors.forename: Adriana Bittencourt
authors.initials: AB
authors.lastname: Campaner
authors.forename: Maria Antonieta Longo Galvão
authors.initials: MA
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000473:pathology / Q000601:surgery; D019092:Conization / Q000379:methods*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers
keywords: Cyclin-Dependent Kinase Inhibitor p16; cervical intraepithelial neoplasia; conization; recurrence