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Immunohistochemistry was used to investigate the expression of tissue factor (TF) as a coagulation factor and thrombomodulin (TM) as an anticoagulation cofactor in the epidermis. TM was expressed on Malpighian layer keratinocytes while TF was located on the supra-Malpighian layer. Epidermal shave extracts were biologically active for both factors. Keratinocytes cultured in high calcium, but not low calcium media, expressed both TF and TM. In pemphigus vulgaris pemphigus foliaceus and bullous pemphigoid, TF expression was increased on keratinocytes shielding the blister compared to the down-regulated TM expression by keratinocytes around the blister.

In normal human skin,, immunoreactive thrombomodulin (TM) is expressed in a strict differentiation related pattern, solely in suprabasal spinous layer keratinocytes. To evaluate the potential application of TM as a differentiation marker for keratinocyte-derived skin tumours, we have studied immunohistopathological, biochemical and functional TM activities in various skin tumours. Immunoreactive, full sized and enzymatically active TM was expressed in keratinocyte-derived skin tumours (squamous cell carcinoma, seborrhoeic keratosis and partly Bowen's disease), as well as normal epidermal keratinocytes and endothelial cells. However, no TM was detected in basal cell carcinomas, senile keratosis or non-squamous epithelial tumours such as malignant melanoma, naevus pigmentosus and Paget's disease. Interestingly, decreased expression was observed in verruca vulgaris. These findings suggested that differentiation-dependent TM expression was restricted to epithelial skin tumours and undetectable on neural crest derived tumours. TM is a differentiation marker for spinous layer keratinocytes and is a useful tool in histopathological study of epithelial tumours.

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