Comparison of the Expression of Cytokeratin 6 and 16 in Oral Lichen Planus, Oral Lichenoid Lesions with Dysplasia and Oral Squamous Cell Carcinoma
-
Elaheh Bahreini
,
Nazanin Mahdavi
,
Monir Moradzadeh Khiavi
,
Abdolreza Mohamadnia
,
Mahta Malek
,
Naghmeh Bahrami
Abstract
Introduction: Oral lichen planus (OLP) and oral lichenoid lesions (OLL/OLR) are chronic inflammatory disorders of the oral mucosa with potential malignant transformation. Cytokeratins 6 and 16 (CK6, CK16) are markers of epithelial proliferation and have previously been reported to be elevated in inflammation, wound healing, and epithelial tumors. This study aimed to compare CK6 and CK16 mRNA expression across reticular OLP (ROLP), erosive OLP (EOLP), oral lichenoid lesions with dysplasia (OLR + D), oral squamous cell carcinoma (OSCC), and healthy controls. Materials and Methods: A cross-sectional study was performed on 90 archived oral tissue specimens. mRNA expression was quantified using qRT-PCR, and data were analyzed using ΔCt, ΔΔCt, and fold-change values. Statistical comparisons were made using one-sample t-tests and one-way ANOVA. Results: CK6 and CK16 expression were significantly altered in all lesion groups compared with controls (p < 0.001). Fold‑change analysis showed a slight decrease in CK6 expression in ROLP (0.63‑fold), followed by progressive increases in EOLP (1.59‑fold), OLR + D (1.85‑fold), and OSCC (2.33‑fold). CK16 expression increased from ROLP (1.36‑fold), EOLP (1.47‑fold), and OLR + D (2.00‑fold) to OSCC (2.72‑fold). However, no statistically significant differences were observed among the lesion groups for either gene (CK6: p = 0.840; CK16: p = 0.946). Conclusion: CK6 and CK16 expression increases along the spectrum of oral epithelial lesions but does not reliably distinguish inflammatory, dysplastic, and malignant lesions. These cytokeratins primarily reflect generalized inflammatory and reparative processes, and their interpretation should be integrated with histopathology, clinical findings, and additional molecular markers. Keywords: Lichen planus; Oral lichenoid lesions; Oral squamous cell carcinoma; Epithelial dysplasia; Cytokeratin.
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25. Kaminagakura E, Bonan P, Lopes M, Almeida O, Scully C. Cytokeratin expression in pseudoepitheliomatous hyperplasia of oral paracoccidioidomycosis. Medical Mycology. 2006;44(5):399-404.
26. Sesterhenn AM, Mandic R, Dünne AA, Werner JA. Cytokeratins 6 and 16 are frequently expressed in head and neck squamous cell carcinoma cell lines and fresh biopsies. Anticancer research. 2005;25(4):2675-80.
27. Frohwitter G, Buerger H, Van Diest PJ, Korsching E, Kleinheinz J, Fillies T. Cytokeratin and protein expression patterns in squamous cell carcinoma of the oral cavity provide evidence for two distinct pathogenetic pathways. Oncology letters. 2016;12(1):107-13.
28. Fillies T, Werkmeister R, Packeisen J, Brandt B, Morin P, Weingart D, et al. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity. BMC cancer. 2006;6(1):10.
29. Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, et al. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics. Oral oncology. 2021;121:105451.
30. Jacques CM, Pereira AL, Maia V, Cuzzi T, Ramos-e-Silva M. Expression of cytokeratins 10, 13, 14 and 19 in oral lichen planus. Journal of oral science. 2009;51(3):355-65.
31. de Gutierrez ER, Innocenti AC, Cippitelli MJ, Salomón S, Vargas-Roig LM. Determination of cytokeratins 1, 13 and 14 in oral lichen planus. Medicina Oral, Patologia Oral Y Cirugia Bucal. 2014;19(4):e359.
32. Elango T, Sun J, Zhu C, Zhou F, Zhang Y, Sun L, et al. Mutational analysis of epidermal and hyperproliferative type I keratins in mild and moderate psoriasis vulgaris patients: a possible role in the pathogenesis of psoriasis along with disease severity. Human genomics. 2018;12(1):27.
33. Agha-Hosseini F, Khalili M, Rohani B. Immunohistochemistry analysis of P53 and Ki-67 proteins in oral lichen planus and normal oral mucosa. Iranian Journal of Public Health. 2009;38(2):37-43.
2. Kamath VV, Setlur K, Yerlagudda K. Oral lichenoid lesions-a review and update. Indian journal of dermatology. 2015;60(1):102.
3. Carrozzo M, Porter S, Mercadante V, Fedele S. Oral lichen planus: A disease or a spectrum of tissue reactions? Types, causes, diagnostic algorhythms, prognosis, management strategies. Periodontology 2000. 2019;80(1):105-25.
4. Ramos‐García P, González‐Moles MÁ, Warnakulasuriya S. Oral cancer development in lichen planus and related conditions—3.0 evidence level: A systematic review of systematic reviews. Oral diseases. 2021;27(8):1919-35.
5. González-Moles MÁ, Ramos-García P. An evidence-based update on the potential for malignancy of oral lichen planus and related conditions: a systematic review and meta-analysis. Cancers. 2024;16(3):608.
6. Elenbaas A, Enciso R, Al-Eryani K. Oral lichen planus: a review of clinical features, etiologies, and treatments. Dentistry Review. 2022;2(1):100007.
7. Mahdavi N, Aminishakib P, Soltani N. Presence of b cells and plasma cells in oral lichen planus. Journal of Dentistry. 2020;21(3):209.
8. Boñar-Alvarez P, Sayáns MP, Garcia-Garcia A, Chamorro-Petronacci C, Gándara-Vila P, Luces-González R, et al. Correlation between clinical and pathological features of oral lichen planus: A retrospective observational study. Medicine. 2019;98(8):e14614.
9. Van der Meij E, Van der Waal I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. Journal of oral pathology & medicine. 2003;32(9):507-12.
10. Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions: a systematic review. The Journal of the American Dental Association. 2014;145(1):45-56.
11. González-Moles MÁ, Ruiz-Avila I, Gonzalez-Ruiz L, Ayen A, Gil-Montoya JA, Ramos-Garcia P. Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis. Oral oncology. 2019;96:121-30.
12. Giuliani M, Troiano G, Cordaro M, Corsalini M, Gioco G, Lo Muzio L, et al. Rate of malignant transformation of oral lichen planus: A systematic review. Oral diseases. 2019;25(3):693-709.
13. Zhang X, Yin M, Zhang L-j. Keratin 6, 16 and 17—critical barrier alarmin molecules in skin wounds and psoriasis. Cells. 2019;8(8):807.
14. Awasthi P, Thahriani A, Bhattacharya A. Keratins or cytokeratins-a review article. Journal of Advanced Medical and Dental Sciences Research. 2016;4(4):140.
15. Kumar A, Jagannathan N. Cytokeratin: A review on current concepts. proteins. 2018;8:10.
16. Nanda KDS, Ranganathan K, Devi U, Joshua E. Increased expression of CK8 and CK18 in leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma: an immunohistochemistry study. Oral surgery, oral medicine, oral pathology and oral radiology. 2012;113(2):245-53.
17. Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S, et al. Oral squamous cell carcinomas: state of the field and emerging directions. International journal of oral science. 2023;15(1):44.
18. de Carvalho Melo BA, Vilar LG, de Oliveira NR, de Lima PO, de Barros Pinheiro M, Domingueti CP, et al. Human papillomavirus infection and oral squamous cell carcinoma-a systematic review. Brazilian journal of otorhinolaryngology. 2021;87(3):346-52.
19. Babaei P, Abbasi AJ, Mohamadnia A, Malek M, Farhangiyan M, Bahrami N. Evaluation of NCBP2 Gene Expression in Patients with Oral Squamous Cell Carcinoma Compared to Healthy Individuals. Journal of Craniomaxillofacial Research. 2025:100-5.
20. Karimi A, Bahrami N, Sayedyahossein A, Derakhshan S. Evaluation of circulating serum 3 types of microRNA as biomarkers of oral squamous cell carcinoma; A pilot study. Journal of Oral Pathology & Medicine. 2020;49(1):43-8.
21. Roshandel G, Ferlay J, Ghanbari‐Motlagh A, Partovipour E, Salavati F, Aryan K, et al. Cancer in Iran 2008 to 2025: recent incidence trends and short‐term predictions of the future burden. International journal of cancer. 2021;149(3):594-605.
22. Rezapour A, Jahangiri R, Olyaeemanesh A, Kalaghchi B, Nouhi M, Nahvijou A. The economic burden of oral cancer in Iran. PloS one. 2018;13(9):e0203059.
23. Saeed S, Choudhury P, Ahmad SA, Alam T, Panigrahi R, Aziz S, et al. Vitamin D in the treatment of oral lichen planus: A systematic review. Biomedicines. 2022;10(11):2964.
24. Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. Keratin gene mutations in disorders of human skin and its appendages. Archives of biochemistry and biophysics. 2011;508(2):123-37.
25. Kaminagakura E, Bonan P, Lopes M, Almeida O, Scully C. Cytokeratin expression in pseudoepitheliomatous hyperplasia of oral paracoccidioidomycosis. Medical Mycology. 2006;44(5):399-404.
26. Sesterhenn AM, Mandic R, Dünne AA, Werner JA. Cytokeratins 6 and 16 are frequently expressed in head and neck squamous cell carcinoma cell lines and fresh biopsies. Anticancer research. 2005;25(4):2675-80.
27. Frohwitter G, Buerger H, Van Diest PJ, Korsching E, Kleinheinz J, Fillies T. Cytokeratin and protein expression patterns in squamous cell carcinoma of the oral cavity provide evidence for two distinct pathogenetic pathways. Oncology letters. 2016;12(1):107-13.
28. Fillies T, Werkmeister R, Packeisen J, Brandt B, Morin P, Weingart D, et al. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity. BMC cancer. 2006;6(1):10.
29. Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, et al. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics. Oral oncology. 2021;121:105451.
30. Jacques CM, Pereira AL, Maia V, Cuzzi T, Ramos-e-Silva M. Expression of cytokeratins 10, 13, 14 and 19 in oral lichen planus. Journal of oral science. 2009;51(3):355-65.
31. de Gutierrez ER, Innocenti AC, Cippitelli MJ, Salomón S, Vargas-Roig LM. Determination of cytokeratins 1, 13 and 14 in oral lichen planus. Medicina Oral, Patologia Oral Y Cirugia Bucal. 2014;19(4):e359.
32. Elango T, Sun J, Zhu C, Zhou F, Zhang Y, Sun L, et al. Mutational analysis of epidermal and hyperproliferative type I keratins in mild and moderate psoriasis vulgaris patients: a possible role in the pathogenesis of psoriasis along with disease severity. Human genomics. 2018;12(1):27.
33. Agha-Hosseini F, Khalili M, Rohani B. Immunohistochemistry analysis of P53 and Ki-67 proteins in oral lichen planus and normal oral mucosa. Iranian Journal of Public Health. 2009;38(2):37-43.
| Files | ||
| Issue | Vol 12, No 4 (Autumn 2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Lichen planus; Oral lichenoid lesions; Oral squamous cell carcinoma; Epithelial dysplasia; Cytokeratin. | ||
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How to Cite
1.
Bahreini E, Mahdavi N, Moradzadeh Khiavi M, Mohamadnia A, Malek M, Bahrami N. Comparison of the Expression of Cytokeratin 6 and 16 in Oral Lichen Planus, Oral Lichenoid Lesions with Dysplasia and Oral Squamous Cell Carcinoma. J Craniomaxillofac Res. 2026;12(4):231-240.
