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Oral lichen planus treated with 13-cis-retinoic acid (isotretinoin): effects on the apoptotic process

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Abstract

The aim of the present study is to verify the efficacy of isotretinoin in oral lichen planus (OLP). In a double-blind study, ten patients with biopsy-proven OLP were treated for 4 months with 0.1% isotretinoin gel and another ten patients with placebo. At the end of the first period of observation, the patients who had been given the placebo were given isotretinoin for a further 4 months. A complete response was defined as the disappearance of the lesions as assessed by inspection, whereas a partial response was defined as a 50% or more reduction in the size of the lesions. All patients treated with isotretinoin showed a significant improvement of the oral lesions, whereas in the patients who were given the placebo, the size of the lesions remained the same. The patients who were given isotretinoin after the placebo showed a reduction in lesions. In total, there were ten complete and ten partial responses. Lesions were analysed histologically and immunohistochemically with antibodies against bcl-2 and Ki-67. Ki-67 and bcl-2 have statistical significant increased values from before to after treatment, whereas apoptotic bodies decreased one. All these facts could have contributed to the partial or complete regression of OLP lesions. The increase in Ki-67 positive cells show that the epithelium requires for enhanced proliferation and healing. The present results revealed a disturbed cell death programme in OLP that could underline an abnormal epithelial differentiation. The results of this pilot study show that the topical use of isotretinoin is effective in treating OLP.

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References

  1. Da Silva Fonseca M, Do Carmo MAV (2001) Identification of the AgNORs, PCNA and CK16 proteins in oral lichen planus lesions. Oral Dis 7:344–348

    Article  PubMed  Google Scholar 

  2. Dekker NP, Lozada-Nur F, Lagenaur LA, MacPhail LA, Bloom CY, Regezi JA (1997) Apoptosis-associated markers in oral lichen planus. J Oral Pathol Med 26:170–175

    Article  PubMed  Google Scholar 

  3. Flohil CC, Janssen PA, Bosman FT (1996) Expression of bcl-2 protein in hyperplastic polyps, adenomas, and carcinomas of the colon. J Pathol 178:393–397

    Article  PubMed  Google Scholar 

  4. Harada H, Mitsuyasu T, Seta Y, Maruoka Y, Toyoshima K, Yasumoto S (1998) Overexpression of bcl-2 protein inhibits terminal differentiation of oral keratinocytes in vitro. J Oral Pathol Med 27:11–17

    Article  PubMed  Google Scholar 

  5. Hirota M, Ito T, Okudela K, Kawabe R, Yazawa T, Hayashi H, Nakatani Y, Fujita K, Kitamura H (2002) Cell proliferation activity and the expression of cell cycle regulatory proteins in oral lichen planus. J Oral Pathol Med 31:204–212

    Article  PubMed  Google Scholar 

  6. Kalemkerian GP, Ramrath N (1996) Retinoids and apoptosis in cancer therapy. Apoptosis 1:11–24

    Article  Google Scholar 

  7. Karatsaidis A, Schreurs O, Helgeland K, Axell T, Schenk K (2003) Erythematous and reticular forms of oral lichen planus and oral lichenoid reactions differ in pathological features related to disease activity. J Oral Pathol Med 32:275–281

    PubMed  Google Scholar 

  8. Kawamura E, Nakamura S, Sasaki M, Ohyama Y, Kadena T, Kumamaru W, Shirasuna K (2003) Accumulation of oligoclonal T cells in the infiltrating lymphocytes in oral lichen planus. J Oral Pathol Med 32:282–289

    PubMed  Google Scholar 

  9. Lo Muzio L, della Valle A, Mignogna MD, Pannone G, Bucci P, Bucci E, Sciubba J (2001) The treatment of oral aphthous ulceration or erosive lichen planus with topical clobetasol propionate in three preparations: a clinical and pilot study on 54 patients. J Oral Pathol Med 30:611–617

    Article  PubMed  Google Scholar 

  10. Lotan R, Xu XC, Lippman SM, RO JY, Lee JS, Lee JJ, Hong WK (1995) Suppression of retinoic acid receptor-β in premalignant oral lesions and its up-regulation by isotretinoin. N Engl J Med 332:1405–1410

    Article  PubMed  Google Scholar 

  11. Lu QL, Abel P, Foster CS, Lalani EN (1996) Bcl-2 role in epithelial differentiation and oncogenesis. Hum Pathol 27:102–110

    Article  PubMed  Google Scholar 

  12. Oridate N, Suzuki S, Higuchi M, Mitchell MF, Ong WK, Lotan R (1997) Involvement of reactive oxygen species in N-(4-hydroxyphenyl) retinamide-induced apoptosis in cervical carcinoma cells. J Natl Cancer Inst 89:1191–1198

    Article  PubMed  Google Scholar 

  13. Petruzzi M, De Benedittis M, Grassi R, Cassano N, Vena G, Serpico R (2002) Oral lichen planus: a preliminary clinical study on treatment with tazarotene. Oral Dis 8:291–295

    Article  PubMed  Google Scholar 

  14. Ramsay JA, From L, Kahn HJ (1995) Bcl-2 protein expression in melanocytic neoplasms of the skin. Mod Pathol 8:150–154

    PubMed  Google Scholar 

  15. Scardina GA, Messina P, Carini F, Maresi E (2006) A randomized trial assessing the effectiveness of different concentrations of isotretinoin in the management of lichen planus. Int J Oral Maxillofac Surg 35:67–71

    Article  PubMed  Google Scholar 

  16. Shalinsky DR, Bischoff ED, Gregory ML, Gottardis MM, Hayes JS, Lamph WW, Heyman RA, Shirley MA, Cooke TA, Davies PJ et al (1995) Retinoid induced suppression of squamous cell differentiation in human oral squamous cell carcinoma xenografts (line 1483) in athymic nude mice. Cancer Res 55:3183–3191

    PubMed  Google Scholar 

  17. Sklavounou A, Chrysomali E, Scorilas A, Karameris A (2000) TNF-alpha expression and apoptosis-regulating proteins in oral lichen planus: a comparative immunohistochemical evaluation. J Oral Pathol Med 29:370–375

    Article  PubMed  Google Scholar 

  18. Ter Hamsel B, Smedts F, Kuijpers J, Jeunink M, Trimbos B, Ramaekers F (1996) bcl-2 Immunoreactivity increases with severity of CIN: a study of normal cervical epithelia, CIN, and cervical carcinoma. J Pathol 179:26–30

    Article  Google Scholar 

  19. Thongprasom K, Luengvisut P, Wongwatanakij A, Boonjatturus C (2003) Clinical evaluation in treatment of oral lichen planus with topical fluocinolone acetonide: a 2-year follow-up. J Oral Pathol Med 32:315–322

    Article  PubMed  Google Scholar 

  20. Tjalma W, Weyler J, Goovaerts G, De Pooter C, Van Marck E, Van Dam P (1997) Prognostic value of bcl-2 expression in patients with operable carcinoma of the uterine cervix. J Clin Pathol 50:33–36

    Article  PubMed  Google Scholar 

  21. Toma S, Mangiante PE, Margarino G, Nicolò G, Palumbo R (1992) Progressive 13-cis-retinoic acid dosage in the treatment of oral leukoplakia. Eur J Cancer B Oral Oncol 28B:121–123

    Article  PubMed  Google Scholar 

  22. Villaroel Dorrego M, Correnti M, Delgado R, Tapia FJ (2002) Oral lichen planus: immunohistology of mucosal lesions. J Oral Pathol Med 31:410–414

    Article  Google Scholar 

  23. Zhao ZZ, Savage NW, Sugerman PB, Walsh LJ (2002) Mast cell/T cell interactions in oral lichen planus. J Oral Pathol Med 31:189–195

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was partly supported by the National Research Council, Rome, Italy and by the Ministry of University, Research, Science and Technology, Rome, Italy.

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Correspondence to Francesco Carinci.

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Piattelli, A., Carinci, F., Iezzi, G. et al. Oral lichen planus treated with 13-cis-retinoic acid (isotretinoin): effects on the apoptotic process. Clin Oral Invest 11, 283–288 (2007). https://doi.org/10.1007/s00784-007-0117-0

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  • DOI: https://doi.org/10.1007/s00784-007-0117-0

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