title: High-risk HPV infection and CIN grade correlates to the expression of c-myc, CD4+, FHIT, E-cadherin, Ki-67, and p16INK4a.
abstract: OBJECTIVE
  : This study aimed to investigate correlations between a panel of biomarkers/tumor markers and high-risk (HR) human papillomavirus (HPV)-positive versus HR-HPV-negative cervical lesions.
  
  
  METHODS
  : The study included 188 women who consecutively attended a colposcopy clinic because of PAP smears suggesting cervical intraepithelial neoplasia (CIN), and 40 women with normal vaginal cytology. Tissue microarray blocks were prepared from representative cervical cone or punch biopsies. Sections were stained for 12 biological markers, previously shown to be relevant in cervical neoplasms, and expression was correlated to the presence or absence of HR-HPV in cervical lesions.
  
  
  RESULTS
  : No correlations between expression of biomarkers and HPV status were found in normal epithelium. Expression of c-myc, CD4, Ki-67, and p16 correlated significantly to HR-HPV-infected epithelium compared with HR-HPV-negative epithelium. When adjustment was made for CIN grade, only the expression of Ki-67 correlated significantly with HPV status and CIN grade. Human papillomavirus status was stratified to normal epithelium, low-grade CIN, and high-grade CIN. Fragile histidine triad (FHIT), E-cadherin, Rb, Ki-67, and p16 expression was significantly increased in HPV-positive tissue by increasing CIN grade. No correlation to tumor marker expression was observed in the HPV-negative tissue.
  
  
  CONCLUSIONS
  : This study described correlations, previously not investigated, between HPV status and tumor marker expression, that is, E-cadherin, Rb, and fragile histidine triad. Surprisingly, p16 was not, although Ki-67 expression was, independently correlated to HPV positivity. The results of this study suggest that p16 instead correlates independently with increasing CIN grade.
authors.affiliation: Department of Obstetrics and Gynecology, Falun Hospital, Sweden. raghad.samir@ltdalarna.se
authors.forename: Raghad
authors.initials: R
authors.lastname: Samir
authors.forename: Anna
authors.initials: A
authors.lastname: Asplund
authors.forename: Tibor
authors.initials: T
authors.lastname: Tot
authors.forename: Gyula
authors.initials: G
authors.lastname: Pekar
authors.forename: Dan
authors.initials: D
authors.lastname: Hellberg
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000032:analysis; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D015820:Cadherins / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D012720:Severity of Illness Index; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D015415:Biomarkers; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D000099170:Bis(5'-adenosyl)triphosphatase; C489427:MYC protein, human