Expression of caspase 14 and filaggrin in oral squamous carcinoma

Abstract

Caspase 14 is one of the latter discovered members of the caspase enzyme family and, although sharing sequence homologies with the other caspases, it is not involved in apoptosis. Together with its co-factor filaggrin, it plays an important role in skin barrier formation. It is already known that caspase 14 proteins are reduced during neoplastic dedifferentiation in cervical intraepithelial neoplasms and in invasive cervical carcinomas. Oral squamous carcinoma tissues have not been systematically evaluated for caspase 14 expression yet. Formalin-fixed and paraffin-embedded samples from oral squamous carcinomas (n = 36 tumours from 34 patients), metastases (n = 15) and controls (leukoplakia, n = 10) were analysed by immunohistochemistry. In carcinomas, human papilloma virus (HPV) infection was tested by PCR. Here we demonstrate that, in oral epithelia, caspase 14 is expressed mainly by cells of the intermediate and superficial cell layers while filaggrin is expressed only in keratinising foci in leukoplakia. Caspase 14 and filaggrin are co-localised. In invasive oral carcinomas, reduced expression of caspase 14 was detectable in 47 % of tumours but was not associated with keratinisation, tumour differentiation or HPV infection. Filaggrin was detectable in a subfraction of tumours (56 %) and was restricted to keratinising areas of the carcinomas. In summary, in contrast to cervical carcinomas, partial loss of caspase 14 is not associated with dedifferentiation in neoplastic lesions of the oral mucosa or HPV infection.

Fig. 1

Protein expression of caspase 14 and its co-factor filaggrin in oral squamous lesions. a In leukoplakia, caspase 14 is mainly expressed in the suprabasal cell layers and the intensity of protein expression increases from basal to apical. b Site of transition between normal, non-keratinising squamous epithelia without filaggrin expression and leukoplakia with expression of the caspase 14 co-factor filaggrin. Caspase 14 and filaggrin are co-localised in areas of keratinisation (see supplementary Figure 1). c In high-grade dysplasia, caspase 14 expression is not reduced and the baso-apical increase of protein expression is preserved. d In caspase 14-positive carcinoma, the expression pattern mimicked leukoplakia: in caspase 14, expression is increased in keratinising foci, while peripheral carcinoma cells show a weaker expression. e Filaggrin expression was less intense and fewer tumour cells in keratinising foci were positive. f Almost absent caspase 14 expression in a keratinising oral carcinoma. g Keratinising carcinoma without filaggrin expression. Original magnification in all images ×100