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Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions

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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.

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Acknowledgments

This work was supported by grants-in-aid for scientific research projects on smoking and health from the Smoking Research Foundation of Japan.

Conflict of interest

No author has any conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan

    Morihiko Inamine, Yutaka Nagai & Yoichi Aoki

  2. Departments of Reproductive Medicine/Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Akira Mitsuhashi

  3. Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Satoru Nagase & Nobuo Yaegashi

  4. Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    Hiroyuki Yoshikawa

Authors
  1. Morihiko Inamine
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  2. Yutaka Nagai
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  3. Akira Mitsuhashi
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  4. Satoru Nagase
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  5. Nobuo Yaegashi
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  6. Hiroyuki Yoshikawa
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  7. Yoichi Aoki
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Corresponding author

Correspondence to Yoichi Aoki.

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Inamine, M., Nagai, Y., Mitsuhashi, A. et al. Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions. Int J Clin Oncol 17, 498–504 (2012). https://doi.org/10.1007/s10147-011-0322-3

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  • DOI: https://doi.org/10.1007/s10147-011-0322-3

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