Abstract
Objectives
The aim of this study was to investigate the relationship the expression of cytokeratins (CK10 and CK13) and the cell proliferation index determined by Ki-67 of lip squamous cell carcinoma and actinic cheilitis with different degrees of dysplasia.
Materials and methods
Forty-five paraffin-embedded actinic cheilitis with and without dysplasia and 20 lip squamous cell carcinoma were analyzed by immunohistochemistry using anti-human anti-CK10, anti-CK13, and anti-Ki-67 antibodies.
Results
The majority of actinic cheilitis showed immunopositivity for CK10 and CK13 with decrease or loss of expression in dysplastic areas. In lip squamous cell carcinoma of the lip, heterogeneous expression of CK13 and immunonegativity for CK10 were observed. There was a statistically significant difference between CK10 expression in lip squamous cell carcinoma and in actinic cheilitis with or without dysplasia (p < 0.001). The cell proliferation index was higher in actinic cheilitis with dysplasia and lip squamous cell carcinoma than in actinic cheilitis without epithelial dysplasia. A significant correlation was found between the intensity of the epithelial dysplasia and the cell proliferation index (p < 0.001).
Conclusion
These results provide evidence that there is a downregulation of CK10 expression in dysplastic areas of patients with actinic cheilitis and in those with lip squamous cell carcinoma (LSCC) and that the index of cell proliferation, determined by Ki-67, is directly correlated with the intensity of the epithelial dysplasia.
Clinical relevance
Altogether, these results suggest that CK10 expression and the epithelial cell proliferation index can help to identify malignant transformation in the lip region.
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References
Bouquot J, Speight PM, Farthing PM (2006) Epithelial dysplasia of the oral mucosa—diagnostic problems and prognostic features. Current Diagnostic Pathology 12:11–12
Speight PM (2010). An overview of the classification and predictive value of oral epithelial dysplasia [http://www.iaop.com/docs/epithelial%20dysplasia.pdf] Accessed 26 June 2012.
Gale N, Pilch BZ, Sidransky D, Westra WH, Califano J (2005) Epithelial precursor lesions. In: Barnes L, Eveson JW, Reichart P, Sidransky D (eds) World Health Organization Classification of Tumours. Pathology and genetics: head and neck tumours. IARC Press, Lyon, pp 140–142
Kujan O, Khattab A, Oliver RJ, Roberts SA, Thakker N, Sloan P (2007) Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation. Oral Oncol 43(3):224–31
Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E (2008) Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 37(3):127–33
Wood NH, Khammissa R, Meyerov R, Lemmer J, Feller L (2011) Actinic cheilits: a case report and review of the literature. Eur J Dent 5(1):101–6
Jadotte YT, Schwartz RA (2012) Solar cheilosis: an ominous precursor: part I. Diagnostic insights. J Am Acad Dermatol 66(2):173–84
Vieira RA, Minicucci EM, Marques ME, Marques AS (2012) Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects. An Bras Dermatol 87(1):105–14
Menta Simonsen Nico M, Rivitti EA, Lourenço SV (2007) Actinic cheilitis: histologic study of the entire vermilion and comparison with previous biopsy. J Cutan Pathol 34(4):309–14
dos Santos JN, de Sousa SO, Nunes FD, Sotto MN, de Araújo VC (2003) Altered cytokeratin expression in actinic cheilitis. J Cutan Pathol 30(4):237–41
Gires O, Mack B, Rauch J, Matthias C (2006) CK8 correlates with malignancy in leukoplakia and carcinomas of the head and neck. Biochem Biophys Res Commun 343(1):252–9
Fillies T, Jogschies M, Kleinheinz J, Brandt B, Joos U, Buerger H (2007) Cytokeratin alteration in oral leukoplakia and oral squamous cell carcinoma. Oncol Rep 18(3):639–43
Ohta K, Ogawa I, Ono S, Taki M, Mizuta K, Miyauchi M, Takechi M, Shigeishi H, Takata T, Kamata N (2010) Histopathological evaluation including cytokeratin 13 and Ki-67 in the border between Lugol-stained and -unstained areas. Oncol Rep 24(1):9–14
Schaaij-Visser TB, Bremmer JF, Braakhuis BJ, Heck AJ, Slijper M, van der Waal I, Brakenhoff RH (2010) Evaluation of cornulin, keratin 4, keratin 13 expression and grade of dysplasia for predicting malignant progression of oral leukoplakia. Oral Oncol 46(2):123–7
Sakamoto K, Aragaki T, Morita K, Kawachi H, Kayamori K, Nakanishi S, Omura K, Miki Y, Okada N, Katsube K, Takizawa T, Yamaguchi A (2011) Down-regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia: a clue for histopathogenesis. Histopathology 58(4):531–42
Ida-Yonemochi H, Maruyama S, Kobayashi T, Yamazaki M, Cheng J, Saku T (2012) Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections. Mod Pathol 25(6):784–94
Kitamura R, Toyoshima T, Tanaka H, Kawano S, Kiyosue T, Matsubara R, Goto Y, Hirano M, Oobu K, Nakamura S (2012) Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma. J Cancer Res Clin Oncol 138(8):1299–310
Kobayashi T, Maruyama S, Abé T, Cheng J, Takagi R, Saito C, Saku T (2012) Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa. Histopathology 61(5):910–20
Gonzalez-Moles MA, Ruiz-Avila I, Rodriguez-Archilla A, Martinez-Lara I (2000) Suprabasal expression of Ki-67 antigen as a marker for the presence and severity of oral epithelial dysplasia. Head Neck 22(7):658–61
Takeda T, Sugihara K, Hirayama Y, Hirano M, Tanuma JI, Semba I (2006) Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias. J Oral Pathol Med 35(6):369–75
González-Moles MA, Bravo M, Ruiz-Avila I, Acebal F, Gil-Montoya JA, Brener S, Esteban F (2010) Ki-67 expression in non-tumour epithelium adjacent to oral cancer as risk marker for multiple oral tumours. Oral Dis 16(1):68–75
Montebugnoli L, Gissi DB, Badiali G, Marchetti C, Cervellati F, Farnedi A, Foschini MP (2011) Ki-67 from clinically and histologically “normal” distant mucosa as prognostic marker in early-stage (T1-T2N0) oral squamous cell carcinoma: a prospective study. J Oral Maxillofac Surg 69(10):2579–84
Acknowledgments
The authors wish to thank the CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and CNPq (N°:141641/2013-4) for supporting this study.
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The authors declare that they have no competing interests.
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Garcia, N.G., Oliveira, D.T., Lauris, J.R.P. et al. Loss of cytokeratin 10 indicates malignant transformation in actinic cheilitis. Clin Oral Invest 20, 745–752 (2016). https://doi.org/10.1007/s00784-015-1557-6
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DOI: https://doi.org/10.1007/s00784-015-1557-6