bromochloroacetic-acid and Carcinoma--Verrucous

Intraepithelial neoplasia of the upper aerodigestive tract (UADT), including both histologically defined dysplasia and carcinoma in situ (CIS), appears to fall into two broad groups similar to intraepithelial neoplasia of other squamous mucosae, keratinizing and non-keratinizing. Keratinizing dysplasia/CIS is common in the UADT and uncommon in other sites such as the cervix. In general, keratinizing epithelial proliferation results in thick epithelium, usually with prominent superficial keratin expression with a whitish or "leukoplakic" clinical appearance. Although most clinical leukoplakic changes in the UADT mucosa do not represent neoplastic transformation and do not progress to invasive carcinoma, keratinizing dysplasia, defined by nuclear atypism and maturation alterations, has an appreciable progression to invasive carcinoma. Non-keratinizing dysplasia/CIS, common in the cervix, is less common in the UADT mucosa. In general, non-keratinizing epithelial alterations consist of a proliferation of incompletely differentiated cells as measured by a spectrum of maturation markers. These changes result in a thin epithelium which commonly has a red, or clinically "erythroplakic," appearance. Non-keratinizing dysplasias are less common, but are more likely to harbor high grade dysplasia or early invasive carcinoma.

Topics: Animals; Carcinoma, Verrucous; Digestive System Neoplasms; Epithelium; Erythroplasia; Humans; Keratins; Leukoplakia; Precancerous Conditions; Respiratory Tract Neoplasms

Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. Squamous cell carcinoma (SCC) represents the second most frequent skin neoplasia with complex aetiology. The molecular events disrupting the orchestrated interplay between the cytoskeleton, cell adhesion molecules and signalling proteins are ill understood in SCC. We describe the molecular background and the unusual course of the disease in a patient with EBS Dowling-Meara, severe keratoderma and a massive verrucous carcinoma. Skin and tumour samples from the patient were analysed using light microscopy, immunohistochemistry and immunofluorescence mapping. Mutation analysis of the KRT5 and KRT14 genes identified the novel KRT5 mutation p.E477D. Invasive tumour areas were characterized by downregulation of keratins 5 and 14, reduced and irregular desmocollin-2 expression and increased expression of keratins 6, 16 and 17. Levels of Ki-67 were increased and levels of E-cadherin strongly reduced in the tumour tissue. In this case a novel KRT5 mutation led to increased fragility of keratinocytes. Desmosome and adherens junctions were destabilized, which may trigger keratinocyte-mediated inflammation, possibly via p120-catenin-dependent signalling, suggesting a link between a keratin mutation and SCC, which adds weight to the hypothesis that disturbance of the cytoskeleton represents a major cause in the appearance of the malignant phenotype. Some individuals with EBS may be at risk of developing secondary SCC.

Topics: Adult; Cadherins; Carcinoma, Verrucous; DNA Mutational Analysis; Down-Regulation; Epidermolysis Bullosa Simplex; Fluorescent Antibody Technique, Indirect; Humans; Immunohistochemistry; Keratin-14; Keratin-5; Keratinocytes; Keratins; Ki-67 Antigen; Mutation; Skin Neoplasms; Tomography, X-Ray Computed

Cytokeratins (CKs) are the intermediate filament proteins of the epithelium cells, which have become important markers of normal and abnormal cell differentiation. The goal of the present study was to investigate the expression pattern of CK 10, 13, 14 and 16 in oral verrucous carcinoma (OVC) and oral squamous papilloma (OSP).. Formalin-fixed paraffin-embedded sections from eight cases of each lesion were assessed. Immunohistochemistry was carried out using streptoavidin-biotin complex method.. In OVC, CK 10 was expressed in suprabasal to superficial layers whereas in OSP mainly in superficial layer. CK 13 was detected in prickle and superficial cells in most cases of OVC and in suprabasal to superficial cells of OSP. All the cell layers of OVC reacted positively for CK 14 while basal and suprabasal layers of OSP were more pronounced for CK 14. Finally, CK 16 was observed in suprabasal to superficial layer in OVC and the majority cases in OSP showed only superficial reactive cells.. CK 10, 13, 14 and 16 immunohistochemical profile emphasis the biological behavior of the studied lesions and confirm the use of these proteins as markers of differentiation.

Topics: Carcinoma, Verrucous; Cell Proliferation; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Mouth Neoplasms; Papilloma

The expression pattern of cytokeratin filaments in epithelia has been shown to be dependent on their type and grade of differentiation. The type of expression of cytokeratin in a cell may also be altered during carcinogenesis or other pathological conditions. The present study examined the alterations in expression of various cytokeratin types during different stages of tumour progression in the oral mucosa. Six monoclonal anti-cytokeratin antibodies were used for the study. Conspicuous staining differences with these antibodies were evident between normal keratinizing and non-keratinizing mucosa. These differences can be correlated to the differentiation pattern of the normal mucosa types. Antibodies specific to cytokeratin types 10/11, 19 and 14 showed significant correlation with stage of tumour progression. In addition cytokeratin type 18 also showed prominent differences in expression between different stages of tumour progression. These alterations in cytokeratin expression suggest that the terminal differentiation pathway of keratinocytes is disturbed during oral carcinogenesis. The results of the present study also emphasize the potential of using cytokeratin filaments as markers in the biological staging of oral premalignant and malignant lesions.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Humans; Immunohistochemistry; Keratins; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Topics: Adenocarcinoma; Antigens, Differentiation; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Cell Differentiation; Electrophoresis, Polyacrylamide Gel; Humans; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Keratoacanthoma; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms