Proto-oncogenes and p53 protein expression in normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia

The aim of this study was to study the protein expression of six proto-onco genes (epidermal growth factor receptor (EC;FR), c-fms, c-myc, c-kit, c-erb B-2 and pan-ras) and one tumour suppressor gene (TP53), by immunohistochemi cal staining of normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia (CIN). Paraffin sections of 45 normal cervical specimens, 38 CIN grade one (CIN1), 37 CIN2 and 43 CIN3 were studied. An im munohistochemical (IHC) score was derived from the intensity of staining an d the percentages of cells stained. In normal cervical specimens, a higher IHC score was found with EGFR and c-fins in superficial (S), intermediate I and parabasal (PB) cells compared with basal cells. In contrast, a higher IHC score was found with c-erbB-2 in basal cells in normal cervical specime ns, Dysplastic cells in CIN had a higher IHC score with c-myc and c-erbB-2 than normal SII and PB cells. Dysplastic cells had a higher score with EGFR than normal basal cells. However, a higher IHC score with EGFR and c-fms w as found in normal SII cells than dysplastic cells. These findings suggeste d that EGFR and c-fms were activated in more differentiated normal cells bu t were less active in less differentiated normal basal cells. However, EGFR was reactivated in dysplastic cells. Meanwhile, c-erbB-2 was activated in less differentiated normal basal cells and dysplastic cells, and was less a ctive in differentiated normal cells. c-myc was activated in dysplastic cel ls, c-fms was more active in more differentiated normal cells and was not a ctivated in less differentiated or dysplastic cells. c-kit, pan-ras and TP5 3 were not activated in normal or dysplastic cervical cells. These results suggest EGFR, c-erbB-2 and c-myc may be important proto-oncogenes in CIN an d that antibodies or anti-genes targeted against them may alter the progres s of CIN to invasive cancer. (C) 1999 Elsevier Science Ltd. All rights rese rved.