title: Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions.
abstract: OBJECTIVE
  Vascular endothelial growth factors (VEGFs) are involved in angiogenesis, but molecular links to the most important etiological agents, human papillomavirus (HPV) and smoking, need to be clarified.
  
  
  METHODS
  Archival samples at the first diagnosis of 64 cervical intraepithelial neoplasia grade 1 or 2 (CIN 1/2) lesions were examined immunohistochemically using anti-VEGF-C and anti-Ki-67 antibodies. HPV types were identified from cervical samples by restriction fragment length polymorphism, which has been shown to identify at least 26 types of genital HPVs. Follow-up data were available for all patients with CIN lesions.
  
  
  RESULTS
  Cervical intraepithelial neoplasia lesions regressed in 47 cases and were persistent in 17 cases. Twenty-two smokers, 8 former smokers, and 34 non-smokers were enrolled in the study. The median observation period was 52.3 months. Significantly higher VEGF-C expression was observed in 8 smokers with persistent CIN persistence (49.0 ± 16.6%, P < 0.01), whereas no significant difference was observed in Ki-67 expression. The median time to regression was significantly longer in the 10 smokers with high VEGF-C expression (48.3 months, P = 0.030) than that in the others. HPV was detected in 56 of the 64 cases. Thirty-two patients had high-risk HPV, 13 had intermediate-risk HPV, and 2 had low-risk HPV. No significant difference was observed among the HPV risk groups in both average Ki-67 and VEGF-C expression.
  
  
  CONCLUSIONS
  These findings suggest that VEGF-C may play an important role in cigarette smoking-associated cervical carcinogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
authors.forename: Morihiko
authors.initials: M
authors.lastname: Inamine
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagai
authors.forename: Akira
authors.initials: A
authors.lastname: Mitsuhashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Aoki
mesh_terms: D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
chemical_list: C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C