Abstract
Immunohistochemical changes of epidermal growth factor receptor (EGFR) during the genesis of tongue carcinomas were studied in male SD rats administered 50ppm 4NQO p.o. for 12 weeks. Paraffin sections were examined with immunohistochemical meth ods using monoclonal anti-EGFR antibody (clone F4), polyclonal anti-EGF antibody, polyclonal anti-TGFα antibody, monoclonal anti-keratin antibody (clone KL1), and monoclonal anti-PCNA antibody (clone PC10) by the ABC method. Immunoblotting for EGFR and keratin was evaluated at 170 k Da and 56 k Da bands. EGFR was expressed in the cell membrane of both non-tumorous epithelial cells and carcinoma cells, and EGFR staining was mostly distributed in the spinous cells of the normal epithelium and its hyperkeratotic or dysplastic counterpart. The staining level of the basal cells was much weaker. In the hyperkeratotic epithelium, the intensity of the staining was stronger than that in the normal epithelium. In carcinoma, EGFR expression was found in the highly differentiated areas of the surrounding cancer pearl, but there was no expression in peripheral tumor calls corresponding to basal cells. Keratin (KL1) reaction was noted in keratinocyte and keratinizing tumor cells, and KL1 positive cells were irregularly distributed in line with keratinization. Such irregular expression of higher molecular weight keratin occured parallel to individual cell keratinization or dysplasia. PCNA positive nuclei were confined to the basal cells and proliferating tumor cells. Immunostaining of EGF and TGFα was limited to the cytoplasm of the spinous cells in normal epithelium and induced carcinoma.
These results suggested the following:
1) In the rat tongue carcinoma induced by 4NQO, EGFR may react by autocrine mechanism of EGF/TGFα during carcinogenesis.
2) Abnormal EGFR expression in carcinoma cells may be involved in malignant transformation.
3) EGF/TGFα-EGFR interaction may be involved in processes after cell division or proliferationboth in the normal epithelium and in squamous cell carcinoma.
4) EGF/TGFα-EGFR interaction may play a part in the control of keratin production in epithelial cells under a physiological environment, and EGFR may be more intimately involved in squamous cell differentiation rather than in cell proliferation in squamous cell epithelium and squamous cell carcinoma.
