epidermal-growth-factor and Keratosis

We set out to investigate the interactions between malignant transformation of keratinocytes, presence of oncoproteins and immunosurveillance in squamous cell carcinoma (SCC) and in a preneoplastic lesion, actinic keratosis (AK).. Samples of SCC, AK and normal skin (NS) were subjected to quantitative analysis using the following antibodies: anti-p53, Ki67, OKT6, OK-DR, B7/BB1, anti-CD54, anti-CD11, OKT3, OKT4, OKT8; positivity for ras-p21, EGFr and bcl-2 was evaluated by semiquantitative analysis.. Oncoprotein alterations and increased keratinocyte proliferative activity were observed both in AK and SCC. The number of Langerhans cells (CD1a+ cells) was similar in the two lesions but lower in SCC compared to AK. The proportion of CD1a(+)-B7/BB1+ cells was slightly higher in AK and SCC than in NS. The Langerhans cells expressed the HLA-DR antigen in all groups. Values were highest in AK and NS, and quite low in SCC. Cytotoxic T lymphocytes were more numerous in SCC than in AK and NS. Interestingly, the total CD4/CD8 ratio was much lower in SCC than in AK and NS, which indicates an increase in the CD8+ subpopulation in samples of SCC. In the epithelia of SCC samples there were a considerable number of B7/BB1+ keratinocytes.. We suggest that alterations in the immunodefence mechanisms have an important role in the transformation of AK into SCC, and that these changes affect not only lymphocytes, but also professional (i.e., Langerhans cells) and non-professional (i.e., keratinocytes) antigen presenting cells.

Topics: Aged; Analysis of Variance; Biopsy, Needle; Carcinoma, Squamous Cell; CD3 Complex; CD4 Antigens; CD8 Antigens; Cell Transformation, Neoplastic; Cells, Cultured; Epidermal Growth Factor; Female; HLA-DR Antigens; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Keratinocytes; Keratosis; Male; Middle Aged; Oncogene Proteins; Precancerous Conditions; Skin Neoplasms

To study the process of aural cholesteatoma formation, we used gerbilline temporal bones to examine histologically the early stages of spontaneous cholesteatomas associated with experimentally induced otitis media with effusion (OME) following electric cauterizations of the eustachian tube. Epidermal growth factor (EGF) was then localized immunohistochemically in the pars flaccida of normal ears and the forming spontaneous cholesteatomas. Findings in the ears with the early spontaneous cholesteatomas were effusion inside the pars flaccida and hypertrophy and hyperkeratosis of the pars flaccida. Findings in the ears with experimental OME involved an effusion in the whole middle ear cavity as well as hypertrophy and hyperkeratosis in both the pars flaccida and pars tensa. The incidence of ear drum changes was higher in the experimental OME group than in control animals without cauterization. EGF was localized in the mucous layer of normal drums, the mucous layer and lamina propria of drums with hypertrophy alone, and all layers in drums with hypertrophy and hyperkeratosis. EGF was especially positive in the cytoplasms of transformed cuboidal cells. These findings suggest that EGF within the transformed mucous layer may play an important role as a biochemical factor in developing cholesteatomas.

Topics: Animals; Cautery; Cholesteatoma, Middle Ear; Cytoplasm; Disease Models, Animal; Epidermal Growth Factor; Epithelium; Eustachian Tube; Gerbillinae; Hypertrophy; Immunohistochemistry; Keratosis; Mucous Membrane; Otitis Media with Effusion; Temporal Bone; Tympanic Membrane

To assess the effects of transforming growth factor alpha (TGF-alpha) on mammalian skin in vivo, we have targeted its expression to the epidermis of transgenic mice using a vector based on the human K1 (HK1) gene. Neonatal mice expressing the HK1.TGF-alpha transgene were often smaller than normal littermates and had precocious eyelid opening and wrinkled, scaly skin with diffuse alopecia. Juvenile transgenic mouse epidermis was uniformly hyperkeratotic, but this pattern was generally less pronounced in adult transgenic mice unless they expressed high levels of the HK1.TGF-alpha transgene. Spontaneous, squamous papillomas occurred at sites of wounding in adult mice expressing high levels of HK1.TGF-alpha; however, most were prone to regression. Immunoreactive TGF-alpha was 2-6 times higher in the epidermis of these HK1.TGF-alpha lines. Immunoreactive epidermal growth factor receptor had a normal pattern of expression in nonphenotypic adult epidermis, but a marked reduction in the receptor population was detected in hyperplastic newborn epidermis and phenotypic adult epidermis. Autoradiographic localization of 125I-epidermal growth factor showed a similar pattern of distribution, suggesting that the sites of increased TGF-alpha expression induced epidermal growth factor receptor down-regulation. These data demonstrate the in vivo effect of deregulated TGF-alpha expression on epidermal proliferation and differentiation and suggest a potential role for TGF-alpha in carcinogenesis and other hyperproliferative epidermal disorders.

Topics: Animals; Base Sequence; Cell Division; Epidermal Growth Factor; Epidermis; ErbB Receptors; Hyperplasia; Keratosis; Mice; Mice, Transgenic; Molecular Sequence Data; Papilloma; Skin Neoplasms; Transforming Growth Factor alpha

In humans, the skin is a particularly sensitive target for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and certain halogenated analogs. Reported lesions include a thickening of the epidermis (acanthosis), hyperkeratosis, and squamous metaplasia of the epithelial lining of the sebaceous glands. In this report we describe ongoing studies on the actions of TCDD on cultured human epidermal cells. This system has been established as an in vitro model for interfollicular epidermal hyperkeratinization. Treatment of newly confluent cultures with TCDD results in enhanced differentiation as judged by histologic examination of the cultures, a decrease in the number of basal proliferating cells, and an increase in the number of envelope competent (differentiating) cells and terminally differentiated cells with highly cross-linked cornified envelopes. Changes in the differentiation program are preceded by a decrease in epidermal growth factor (EGF) binding. The concentration dependence and stereospecificity for these responses suggest the involvement of the Ah receptor. We propose that TCDD modulates normal patterns of epidermal differentiation through direct actions on proliferating basal cells, modulating the responsiveness of these cells to growth factors such as EGF.

Topics: Cell Differentiation; Cell Line; Cells, Cultured; Clone Cells; Dioxins; Epidermal Cells; Epidermal Growth Factor; Epidermis; Humans; Keratins; Keratosis; Male; Polychlorinated Dibenzodioxins; Protein Precursors; Receptors, Aryl Hydrocarbon; Receptors, Drug

Topics: Aged; Cell Division; Cells, Cultured; Child, Preschool; Dermatitis, Seborrheic; Epidermal Growth Factor; Female; Growth Substances; Humans; Keratosis; Lymphocytes; Lymphoma; Sezary Syndrome; Skin; Thymidine; Tritium

The sign of Leser-Trélat is a rare cutaneous manifestation of internal malignancy. Although adenocarcinoma is the most common malignant neoplasm associated with the sign of Leser-Trélat, we report what we believe to be the first case of adenocarcinoma of the duodenum associated with this sign. Because of the location of the tumor, we considered the possibility that the skin changes may be due to increased levels of epidermal growth factor (EGF) in this patient. However, no alteration in urine EGF levels was found.

Topics: Adenocarcinoma, Papillary; Duodenal Neoplasms; Epidermal Growth Factor; Humans; Keratosis; Lymphatic Metastasis; Male; Middle Aged; Skin Manifestations