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Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are important keratinocyte mitogens. Their effects are mediated by a cell membrane receptor (EGFR), quantitative and qualitative abnormalities of which may be responsible for deranged keratinocyte proliferation and differentiation. We have therefore examined EGFR expression immunohistochemically in a variety of benign and malignant epithelial neoplasms using monoclonal antibodies to the extracellular and intracellular receptor domains. In benign tumours (virus wart, seborrhoeic keratosis, keratoacanthoma), there was an ordered pattern of EGFR expression. In malignant tumours (basal and squamous cell carcinoma), there was loss of membrane labelling and cytoplasmic accumulation of the receptor. In premalignant proliferations, there was loss of membrane receptor with either absent cytoplasmic EGFR (actinic keratosis) or cytoplasmic receptor accumulation (Bowen's disease). Evidence of truncated receptors was not found. We suggest that dysregulation of the EGFR may be important in the development of cutaneous epithelial malignancies but that grossly abnormal forms of the receptor do not occur.

Keratinocytes express the macrophage/monocyte antigen CD36 in a variety of inflammatory cutaneous diseases characterised by a T lymphocyte rich infiltrate. Since cell-mediated immune mechanisms also play a role in host responses to skin tumours, we investigated the presence of CD36 antigen on keratinocytes in a range of epidermal cell-derived benign and malignant tumours characterised by a peritumoural, dermal lymphocytic infiltrate. Frozen tissue sections of lesional tissue from a range of epidermally derived tumours were labelled with antibodies to CD1a, CD11b, CD36, and HLA-DR antigens. Benign and malignant squamoproliferative tumour cells exhibited a spectrum of CD36 expression, whereas those of basal cell origin were consistently CD36-. Suprabasal expression of CD36 was present in the normal perilesional epidermis of all tumours studied including basal cell carcinoma. Keratinocyte CD11b expression was not observed. The widespread presence of keratinocyte CD36 positivity in squamoproliferative, but not basal epidermal, tumours suggests its expression may be linked to the degree of keratinocyte differentiation. The stimulus for expression is unknown, but the fact that suprabasal perilesional epidermis expressed CD36 strongly in the absence of infiltrate suggests it may represent a non-specific response by keratinocytes to various stimuli.

The antibody G71 is a murine monoclonal antibody directed against an antigen in the basement membrane zone of many human epithelia. Ultrastructurally it is located in the lamina lucida. The epitope is carried on glycoprotein components with molecular weights of 160, 125 and 115 kilodaltons. The authors examined the immunohistochemical expression of G71 antigen, using a standard indirect immunoperoxidase technique, in benign and malignant tumors derived from the epidermis. G71 staining was consistently absent or reduced around basal cell carcinomas (n = 44). In contrast, G71 was present at the basement membrane zone of squamous cell carcinomas (n = 18) and was also frequently expressed within the cytoplasm and on the cell surface of the malignant keratinocytes. The staining pattern of G71 at the basement membrane zone was essentially normal in keratoacanthomas (n = 10), solar keratoses (n = apart from foci of attenuation. In both seborrheic keratoses and intraepidermal squamous 13), seborrheic keratoses (n = 6), and intraepidermal squamous cell carcinomas (n = 8), cell carcinomas cell-surface and cytoplasmic staining were inconstant features. In conclusion, there appears to be a specific defect of G71 antigen expression in basal cell carcinomas.

Alteration in the major histocompatibility complex (MHC) antigen expression by cutaneous tumours may enable them to escape host defence mechanisms and to invade surrounding tissue. Immunohistochemical studies in a wide range of epidermally derived tumours demonstrated expression by keratinocytes of the class II molecule HLA-DR in squamous cell carcinoma (SCC) (2 of 8 cases) and keratoacanthoma (KA) (2 of 7 cases). Additionally, HLA-DP and DQ were expressed by single cases of SCC and KA, although, unlike the widespread distribution of DR, DP and DQ, were only present on keratinocytes adjacent to the inflammatory infiltrate. Therefore, keratinocytes in cutaneous tumours, like carcinoma cells of the colon and breast, may express class II MHC antigens during tumour growth. Beta-2-microglobulin (B2M), an invariant MHC class I marker, was absent in all cases of basal cell carcinoma. Variable loss of B2M was observed in squamous cell carcinoma, Bowen's disease and actinic keratoses, suggesting reduced B2M expression by dysplastic cells. However, the variability in B2M staining both between and within diagnostic categories restricts it's immunodiagnostic usefulness.

An ultrastructural study of lesional skin from 4 subjects with hyperkeratosis lenticularis perstans (Flegel's disease) demonstrated variable numbers of lamellar bodies of normal size and architecture within cells of the stratum granulosum and the upper stratum spinosum. Their characteristic lamellate inclusions were frequently observed within the intercellular spaces. These observations suggest that the lamellar bodies are qualitatively normal in Flegel's disease.

Tissue from the cutaneous metastases of bronchial carcinoid was examined. Fine argyrophil secretory granules were demonstrated in the cytoplasm of the abnormal cells which showed positive labelling with neuron-specific enolase. Ultrastructural studies revealed numerous electron-dense membrane bound neuro-secretory granules, 50-300 nm in diameter. Other characteristic features included inter-digitating pseudo pod-like processes (up to 2 mu in size) in the cytoplasmic membrane, perinuclear filaments, a well-defined Golgi zone and numerous large mitochondria.

Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pig and human skin. Intradermal injection of Paf-acether elicited an acute inflammatory response in guinea-pig skin (assessed by means of radioisotopic techniques) and acute oedema formation in human skin (assessed by means of weal volume and flare area). Acute inflammatory responses in guinea-pig and human skin are potentiated by the presence of serum albumin, a phospholipid carrier. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are slightly modified by the H1-receptor antagonists, mepyramine and chlorpheniramine. These results indicate that the acute inflammatory response induced by Paf-acether is independent of cyclo-oxygenase products of arachidonic acid and that histamine release has a minor contribution to the inflammatory response induced by Paf-acether.

A study of dermatopathological specimens exhibiting parakeratosis has been made and the parakeratosis classified on morphological and topographical criteria. Twelve patterns of parakeratosis have been identified and their association with particular pathological conditions described.

A patient with contact dermatitis from nickel and cobalt developed sensitivity to chlorocresol contained in topical steroid creams. The use of chlorocresol in aqueous creams and topical steroids is reviewed.