epidermal-growth-factor and Leukoplakia--Oral

The aim of this study was to compare the salivary epidermal growth factor (EGF) levels between patients with oral leukoplakia (OL) and clinically healthy individuals, to evaluate the association between salivary and tissular EGF, and to correlate EGF with clinicopathologic data, including the presence of dysplasia.. Salivary EGF levels were measured in 32 patients and 32 controls. The tissue expressions of EGF and its receptor (EGFR) were immunohistochemically evaluated.. Salivary EGF levels were similar in patients with OL compared with controls. There was no association between the salivary levels and immunohistochemical expression of EGF. An absence of EGF detection by immunohistochemistry was associated with development of multiple lesions. Dysplastic lesions showed a tendency toward presenting higher salivary EGF levels.. Currently, it is not possible to indicate salivary EGF as a biomarker for OL. Further studies are needed to elucidate the role of EGF in oral carcinogenesis. A follow-up study is necessary to evaluate the changes in EGF values following the surgical excision of OL.

Topics: Biomarkers; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Humans; Immunoenzyme Techniques; Leukoplakia, Oral; Male; Middle Aged; Saliva

In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

Topics: Adult; Aged; Amphiregulin; Betacellulin; EGF Family of Proteins; Epidermal Growth Factor; Epiregulin; ErbB Receptors; Female; Gene Expression Profiling; Glycoproteins; Heparin; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Leukoplakia, Oral; Lichen Planus, Oral; Ligands; Male; Middle Aged; Mouth Mucosa; Nerve Growth Factors; Neuregulins; Real-Time Polymerase Chain Reaction; Receptor, ErbB-2; Receptor, ErbB-3; Receptor, ErbB-4; Receptors, Cell Surface; RNA, Messenger; Transforming Growth Factor alpha; Up-Regulation

The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva.. Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of alpha-defensin (DEFA) 1/3, DEFA-4, S100-A7, deleted-in-oral-cancer (Doc) 1, interleukin (IL) 1beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF) alpha, cyclooxygenase (Cox) 2, epidermal growth factor (EGF), keratinocyte growth factor (KGF), transforming growth factor (TGF) beta1, TGF-alpha, collagen-IA1 (Col-1), and tenascin-c were analyzed by real-time reverse-transcription polymerase chain reaction. The proteins encoded by the different genes were visualized by immunostaining.. Compared with healthy gingiva (set as 1), there was an increased gene expression of DEFA-4 (179.2-fold), S100-A7 (25.4-fold), EGF (24.8-fold), TGF-beta1 (25.2-fold), and tenascin-c (34.3-fold) in oral leukoplakia. The expression of IL-1beta and Doc-1 was decreased (0.01-fold and 0.2-fold, respectively).. The combination of an increased expression of the antimicrobial peptide DEFA-4, the oncogene S100-A7, EGF, and tenascin-c, and a decreased Doc-1 expression in oral leukoplakia might characterize its potency of malignant transformation. Chronic inflammation seems not to be involved in the development of this lesion.

Topics: alpha-Defensins; Case-Control Studies; Cell Differentiation; Cell Transformation, Neoplastic; Collagen Type I; Collagen Type I, alpha 1 Chain; Cyclooxygenase 2; Epidermal Growth Factor; Fibroblast Growth Factor 7; Gene Expression Profiling; Gingiva; Humans; Immunohistochemistry; Interleukins; Leukoplakia, Oral; Reference Values; RNA; S100 Calcium Binding Protein A7; S100 Proteins; Tenascin; Transforming Growth Factor alpha; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Tumor Suppressor Proteins

Topics: beta-Defensins; Biomarkers; Carcinoma, Squamous Cell; Epidermal Growth Factor; ErbB Receptors; Erythroplasia; Humans; Leukoplakia, Oral; Mouth Neoplasms; Precancerous Conditions; Prognosis; Transforming Growth Factor alpha; Tumor Suppressor Protein p53

The immunohistochemical localizations of human epidermal growth factor (hEGF) and EGF receptor (EGFr) in oral tissues, including normal mucosa, leukoplakia and squamous cell carcinoma were examined by the use of monoclonal antibodies to hEGF and EGFr. In normal mucosa and leukoplakia, immunostaining of hEGF was limited to an underlying layer of connective tissue near the epithelium. The intensity of extracellular staining appeared to increase with the degree of epithelial malignancy and was eventually most striking in the stroma of invasive carcinoma. The epithelial cells in normal mucosa, leukoplakia, and squamous cell carcinoma showed negligible immunoreactivity for hEGF. Expression of EGFr appeared to be associated with the proliferative activity of cells and/or epithelial malignancy. In normal mucosa, anti-EGFr monoclonal antibody reacted only with the basal cell layer. In all sections of leukoplakia, the positive cells for EGFr were found in the prickle cell layer in addition to the basal cell layer. Most tumour cells in squamous cell carcinoma were strongly positive for EGFr. These findings indicate increased expression of hEGF and EGFr with malignancy. The characteristic localization of extracellular hEGF in the underlying connective tissue and in stroma of oral mucosal tumours suggests a possible epithelial-mesenchymal interaction in hEGF secretion.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epidermal Growth Factor; ErbB Receptors; Humans; Immunohistochemistry; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms

Morphometric assessment including epithelial indices which express morphological features of the epithelium, mitotic index, mean nuclear area, mean form factor of the nucleus and cellular infiltration in the stroma was performed in 14 cases with oral non-dysplastic epithelium and 66 cases with dysplastic epithelium. The results from morphometry showed a close relationship to the histological severity of dysplasia determined by the histological criteria of Bánóczy. Immunohistochemical localization of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and epidermal growth factor (EGF) were investigated in 14 cases of non-dysplastic epithelium, 66 cases of dysplastic epithelium and 16 cases of squamous cell carcinoma, and compared with the morphometric results. Positive rates of CEA and EMA reaction in epithelial dysplasia increased with the advance of the dysplastic grade. Those of EGF reaction decreased with the advance of the dysplastic grade. It is suggested that morphometry and immunohistochemistry are useful in confirmation of the histological severity of oral epithelial dysplasia.

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Chi-Square Distribution; Epidermal Growth Factor; Humans; Immunohistochemistry; Leukoplakia, Oral; Membrane Glycoproteins; Mitotic Index; Mouth Neoplasms; Mucin-1