title: A comparative analysis of clinical and molecular factors with the stage of cervical cancer in a Brazilian cohort.
abstract: Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor.
  
  
  OBJECTIVE
  1) To analyze the expression of Ki-67, p53 and p16(INK4a) in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution.
  
  
  METHODS
  Tissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16(INK4a) were analyzed by immunohistochemistry; clinical data was derived from the chart review.
  
  
  RESULTS
  Advanced tumor stage (III and IV) was strongly associated (p<0.005) with advanced age (>55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (p = 0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8).
  
  
  CONCLUSIONS
  We found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines.
authors.affiliation: Laboratory of Interdisciplinary Medical Research (LIPMED), IOC-Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Amaro-Filho
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Golub
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Cunha
authors.forename: José E
authors.initials: JE
authors.lastname: Levi
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Cecília V
authors.initials: CV
authors.lastname: Andrade
authors.forename: Fabio B
authors.initials: FB
authors.lastname: Russomano
authors.forename: Aparecida
authors.initials: A
authors.lastname: Tristão
authors.forename: Andrea
authors.initials: A
authors.lastname: Pires
authors.forename: Alcina F
authors.initials: AF
authors.lastname: Nicol
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology; D015995:Prevalence; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53