Ki-67, TGF-β1, and elastin content are significantly altered in lip carcinogenesis
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Epithelial changes observed in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC) have been studied using different markers in order to observe diagnostic and prognostic factors for both lesions. The aim of the present study was to analyze Ki-67, TGF-β1, and elastin content in AC and LLSCC to determine the possible role of these proteins in lip carcinogenesis. Medical records of 29 cases of AC and 53 cases of LLSCC were analyzed. Lesions were classified according histological pattern and submitted to immunostaining for Ki-67, TGF-β1, and elastin. Different percentages of Ki-67-positive cells were found in AC depending on the degree of epithelial dysplasia (p < 0.01). An association was also found between the percentage of Ki-67-positive cells and tumor grade in LLSCC (p < 0.01). An inverse correlation was found between Ki-67 and TGF-β1 in AC and LLSCC (p < 0.01). Elastosis was thinner and more discontinuous in LLSCC in comparison to AC, and this difference in the elastin immunolabeling pattern was statistically significant between groups (p < 0.01). The present findings indicate that changes in Ki-67 and TGF-β1 content contribute to lip carcinogenesis. Furthermore, elastin content reflects changes in the extracellular matrix in both AC and LLSCC.
KeywordsOral cancer Prognostic biomarkers Potentially malignant disorders
This study was supported by the Postgraduate Research Group of the Porto Alegre University Hospital (GPPG/FIPE: 12–0176). Santos JN, Meurer L, and Martins MD are research fellows at Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. The author’s would like to thank Dr. Pablo Agustin Vargas (FOP-UNICAMP) for his help with photomicrographs.
Conflicts of interest
- 1.Chen YK, Yang SH, Huang AH, Hsue SS, Lin LM. Aberrant expression in multiple components of the transforming growth factor-β1-induced Smad signaling pathway during 7,12-dimethylbenz[a]anthracene-induced hamster buccal-pouch squamous-cell carcinogenesis. Oral Oncol. 2011;47:262–7.PubMedCrossRefGoogle Scholar
- 20.Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, et al. Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol. 2008;44(5):509–17.PubMedCrossRefGoogle Scholar
- 22.Akhurst RJ, Derynck R. TGF-b signaling in cancer—a double edged sword. Trends Cell Biol. 2001;11:44–51.Google Scholar
- 26.Larroque-Cardoso P, Mucher E, Grazide MH, Josse G, Schmitt AM, Nadal-Wolbold F, Zarkovic K, Salvayre R, Nègre-Salvayre A. 4-Hydroxynonenal impairs transforming growth factor-β1-induced elastin synthesis via epidermal growth factor receptor activation in human and murine fibroblasts. Free Radic Biol Med. 2014 Feb 20. pii: S0891-5849(14)00092-6.Google Scholar
- 27.Barnes L et al. World Health Organization classification of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC Press; 2005.Google Scholar
- 48.Oh JE, Kook JK, Min BM. Sig-h3 induces keratinocyte differentiation via modulation of involucrin and transglutaminase expression through the integrin α3s1 and the phosphatidylinositol 3-kinase/Akt signalling pathway. J Cell Biochem. 2005;280:21629–37.Google Scholar