GROWTH FACTOR AND ONCOGENE EXPRESSION IN KERATOACANTHOMA AND SQUAMOUS CELL CARCINOMA OF SKIN

Abstract

The differentiation between keratoacanthoma (KA) and squamous cell carcinoma (SCC) of skin has always been a diagnostic problem to practising pathologists and clinicians. The considerable overlap of histological, clinical features and biological behaviour oflen makes differentiation between these two lesions difficult if not impossible. The relationship between KA and SCC of skin remains unsettled and controversial. We have studied immunohistochemically the expression of eight growth factors and oncogenes (TGF-?, EGF, EGFR, c-erbB-2, ras, c-myc, p53 and bcl-2) in normal skin, pseudoepitheliomatous hyperplasia, KA, SCC and Bowen's disease to seek to understand better the nature of KA and its relationship to SCC of skin. The growth factors and oncogenes were selected from different functional groups operating at different levels of the growth factor signal transduction pathway so as to provide a comprehensive perspective of the relative roles played by these factors which have profound influence on the proliferation, differentiation, growth and death of cells.

Based on their expression in normal skin, these growth factors and oncogenes could be divided into two categories. The first group consisted of EGFR, e-myc and p53 which were expressed mainly in the basal layer and suprabasal kcratinocytes. They were considered markers of proliferation. Tile second group consisted of TGF-ci, EGF, c-crbB-2 and ras which were expressed mainly in the stratum spinosum particularly the mid and superficial differentiated kcratinocytes. They were considered markers of differentiation. bcl-2, on the other hand, is an anti-apoptotic oncogene.

Our study has shown that markers of differentiation were significantly more extensively expressed in KA while markers of proliferation in SCC. In addition, there were significant qualitative differences in the staining pattern between the two lesions. The distribution of TGF-a, EGF and EGFR in KA was generally even, while uneven patchy staining was characteristic of SCC. Abnormal, irregular membrane and cytoplasmic staining of EGFR was a prominent feature of SCC but was not seen in KA. On the other hand, bcl-2 was not expressed in both KA and invasive SCC. We conclude that the predominant growth factors and oncogenes expressed in KA favour differentiation while whose of sec promote proliferation. We believe that these differences determine the biological behaviour of the lesions. They account for the natural evolution of KA with a tendency to regression and involution and the progressive and aggressive growth of SCC. The findings support the view that KA and sec arc different entities with different growth factor and oncogene activities and biological behaviour.