title: Cox-2, EGFR, and ERBB-2 expression in cervical intraepithelial neoplasia and cervical cancer using an automated imaging system.
abstract: We hypothesized that the activation of cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), and ErbB-2 signaling is required for cervical intraepithelial neoplasia (CIN) lesions to progress to cervical cancer. A retrospective analysis was performed in 179 patients with Stage I squamous cell carcinoma (SCC) and 233 patients with CIN (112 CIN I, 47 CIN II, and 74 CIN III). COX-2, EGFR, and ErbB-2 expression was analyzed by immunohistochemistry using the ACIS III automated imaging system. The mean expression of COX-2, EGFR, and ErbB-2 was compared between the various stages of CIN and SCC. COX-2 mean expression was predominantly cytoplasmic, increasing significantly from CIN I to CIN II, CIN III, and SCC (P<0.001). EGFR mean expression also rose significantly during tumor progression from CIN I to SCC (P=0.001). CIN I samples were negative for ErbB-2 expression. CIN II, CIN III, and SCC were considered positive for ErbB-2 expression in 2.2%, 14%, and 16.2% of cases, respectively. There was also a statistically significant correlation between increase of ErbB-2 positivity from CIN to SCC. We conclude that COX-2, EGFR, and ErbB-2 expression increase significantly during the progression of CIN to cancer.
authors.affiliation: Department of Gynecologic Oncology (E.M.F., G.B., L.Y.K., C.C.F., L.B.-F.) Department of Pathology (F.A.S.), AC Camargo Cancer Hospital Department of Gynecologic Oncology (F.R.G.C., R.L.R.C., J.C.S.G.), Brazilian Institute of Cancer Control Discipline of Gynecologic Oncology Department of Obstetrics and Gynecology (W.J.G.), Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Elza M
authors.initials: EM
authors.lastname: Fukazawa
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.forename: Lillian Y
authors.initials: LY
authors.lastname: Kumagai
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Faloppa
authors.forename: Levon
authors.initials: L
authors.lastname: Badiglian-Filho
authors.forename: Francisco R G
authors.initials: FR
authors.lastname: Coelho
authors.forename: Wagner J
authors.initials: WJ
authors.lastname: Gonçalves
authors.forename: Ronaldo L R
authors.initials: RL
authors.lastname: Costa
authors.forename: João C S
authors.initials: JC
authors.lastname: Góes
mesh_terms: D057205:Automation, Laboratory; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C496540:PTGS2 protein, human; C512478:EGFR protein, human