Abstract
Flaps have been routinely used to reconstruct intraoral defects. Flaps after reconstruction tend to develop, with time, a mucosa-like appearance during a process called “mucosalization.” Many studies have described histological changes of mucosalization, but only a few of them mention the associated clinical factors. Our aim was to determine the possible predictive factors related to mucosalization of flaps employed for oral cavity reconstruction, and to verify whether skin inflammation-specific DNA methylation occurs in mucosalized flaps. In this study, 140 patients underwent reconstruction of the oral cavity defects with flaps, of which 39 showed “mucosalization” changes. Histological changes of “mucosalization” are characterized by inflammatory infiltration, accompanied by a reduction of thickness of the horny layer and elimination of skin appendages. These changes are affected by clinical differences with sex and type and site of flaps. We also found that DNA methyltransferase 1 was highly expressed in the epithelium of mucosalized flaps, and less in unmucosalized flaps, suggesting their involvement in the inflammation-dependent DNA methylation of mucosalization. To summarize, our results demonstrated that most intraorally placed flaps maintain skin features, except in the event of heavy inflammation. Mucosalization varies in association with sex of the subject and type and site of flaps. DNA methyltransferase 1 might correlate with mucosalization, suggesting that DNA methylation may be involved in chronic inflammation in mucosalization.
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Yang GF, Chen PJ, Gao YZ, Liu XY, Li J, Jiang SX, He SP (1997) Forearm free skin flap transplantation: a report of 56 cases. 1981. Br J Plast Surg 50(3):162–165. https://doi.org/10.1016/s0007-1226(97)91363-1
Roumanas ED, Garrett N, Blackwell KE, Freymiller E, Abemayor E, Wong WK, Beumer J 3rd, Fueki K, Fueki W, Kapur KK (2006) Masticatory and swallowing threshold performances with conventional and implant-supported prostheses after mandibular fibula free-flap reconstruction. J Prosthet Dent 96(4):289–297. https://doi.org/10.1016/j.prosdent.2006.08.015
Eliachar I, Sebek BA, Levine S, Tucker HM (1985) Histologic changes in skin implanted into the larynx and trachea by myocutaneous flap reconstruction. Otolaryngol Head Neck Surg 93(6):754–758. https://doi.org/10.1177/019459988509300610
Badran D, Soutar DS, Robertson AG, Reid O, Milne EW, McDonald SW, Scothorne RJ (1998) Behavior of radial forearm skin flaps transplanted into the oral cavity. Clin Anat 11(6):379–389. https://doi.org/10.1002/(sici)1098-2353(1998)11:6<379::aid-ca3>3.0.co;2-h
Khan AL, Cloke DJ, Hodgkinson PD, McLean NR, Soames JV (2001) Do intraoral radial forearm free flaps re-mucosalise and is candida infection relevant? Br J Plast Surg 54(4):299–302. https://doi.org/10.1054/bjps.2001.3574
Sinclair A, Johnston E, Badran DH, Neilson M, Soutar DS, Robertson AG, McDonald SW (2004) Histological changes in radial forearm skin flaps in the oral cavity. Clin Anat 17(3):227–232. https://doi.org/10.1002/ca.10180
Ebersole JL, Steffen MJ, Reynolds MA, Branch-Mays GL, Dawson DR, Novak KF, Gunsolley JC, Mattison JA, Ingram DK, Novak MJ (2008) Differential gender effects of a reduced-calorie diet on systemic inflammatory and immune parameters in nonhuman primates. J Periodontal Res 43(5):500–507. https://doi.org/10.1111/j.1600-0765.2008.01051.x
Timmerman MF, Van der Weijden GA, Abbas F, Arief EM, Armand S, Winkel EG, Van Winkelhoff AJ, Van der Velden U (2000) Untreated periodontal disease in Indonesian adolescents. Longitudinal clinical data and prospective clinical and microbiological risk assessment. J Clin Periodontol 27(12):932–942
Santos F, Dean W (2004) Epigenetic reprogramming during early development in mammals. Reproduction 127(6):643–651. https://doi.org/10.1530/rep.1.00221
Suter MA, Aagaard-Tillery KM (2009) Environmental influences on epigenetic profiles. Semin Reprod Med 27(5):380–390. https://doi.org/10.1055/s-0029-1237426
Zhao M, Lu Q (2018) The aberrant epigenetic modifications in the pathogenesis of psoriasis. J Investig Dermatol Symp Proc 19(2):S81–s82. https://doi.org/10.1016/j.jisp.2018.09.007
Roberson ED, Liu Y, Ryan C, Joyce CE, Duan S, Cao L, Martin A, Liao W, Menter A, Bowcock AM (2012) A subset of methylated CpG sites differentiate psoriatic from normal skin. J Investig Dermatol 132(3 Pt 1):583–592. https://doi.org/10.1038/jid.2011.348
Noh YH, Lee J, Seo SJ, Myung SC (2018) Promoter DNA methylation contributes to human beta-defensin-1 deficiency in atopic dermatitis. Anim Cells Syst 22(3):172–177. https://doi.org/10.1080/19768354.2018.1458652
Hessam S, Gambichler T, Skrygan M, Sand M, Ruddel I, Scholl L, Bechara FG (2018) Reduced ten-eleven translocation and isocitrate dehydrogenase expression in inflammatory hidradenitis suppurativa lesions. Eur J Dermatol 28(4):449–456. https://doi.org/10.1684/ejd.2018.3369
Rountree MR, Bachman KE, Herman JG, Baylin SB (2001) DNA methylation, chromatin inheritance, and cancer. Oncogene 20(24):3156–3165. https://doi.org/10.1038/sj.onc.1204339
Wei WI, Lam KH, Lau WF (1989) Fate of skin element of pectoralis major flap in intraoral reconstruction. Arch Otolaryngol Head Neck Surg 115(3):360–363
Katou F, Motegi K, Tagami H, Shirai N, Echigo S, Nagura H (1999) Unique inflammatory features noted in intraorally transferred skin flaps: correlation with Candida albicans infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87(6):676–684
Dellon AL, Tarpley TM, Chretien PB (1976) Histologic evaluation of intraoral skin grafts and pedicle flaps in humans. J Oral Surg 34(9):789–794
Rawlings A, Harding C, Watkinson A, Banks J, Ackerman C, Sabin R (1995) The effect of glycerol and humidity on desmosome degradation in stratum corneum. Arch Dermatol Res 287(5):457–464
Maria L, Ioannis D, Konstantinos V, Fotis I, Konstantinos A (2017) Histological changes in nasolabial cutaneous flaps employed in intraoral reconstruction. J Maxillofac Oral Surg 16(3):292–299. https://doi.org/10.1007/s12663-016-0916-4
Campois TG, Zucoloto AZ, de Almeida Araujo EJ, Svidizinski TI, Almeida RS, da Silva Quirino GF, Harano RM, Conchon-Costa I, Felipe I (2015) Immunological and histopathological characterization of cutaneous candidiasis. J Med Microbiol 64(8):810–817. https://doi.org/10.1099/jmm.0.000095
Rubino C, Dessy LA, Farace F, Ena P, Mazzarello V (2002) Microscopic and immunohistochemical analysis of the skin changes of free forearm flaps in intraoral reconstruction. Ann Plast Surg 49(4):362–368. https://doi.org/10.1097/00000637-200210000-00005
Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A, MacLeod AR (2003) DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 33(1):61–65. https://doi.org/10.1038/ng1068
Saito S, Kato J, Hiraoka S, Horii J, Suzuki H, Higashi R, Kaji E, Kondo Y, Yamamoto K (2011) DNA methylation of colon mucosa in ulcerative colitis patients: correlation with inflammatory status. Inflamm Bowel Dis 17(9):1955–1965. https://doi.org/10.1002/ibd.21573
Funding
This project was supported by the National Nature Science Foundation of China (No. 81360403) to Feixin Liang. This project was supported by Medical and Health Technology Development and Promotion Application Project of Guangxi (No. S2018067) to Feixin Liang.
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Chen, X., Li, Y., Zhou, Z. et al. Clinical and Histological Features of Intraoral Flap and a Preliminary Study of DNA Methylation of Mucosalization. Indian J Surg 82, 559–565 (2020). https://doi.org/10.1007/s12262-019-02029-5
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DOI: https://doi.org/10.1007/s12262-019-02029-5