EPIDERMAL-GROWTH-FACTOR RECEPTOR CORRELATES NEGATIVELY WITH CELL-DENSITY IN CERVICAL SQUAMOUS EPITHELIUM AND IS DOWN-REGULATED IN CANCERS OF THE HUMAN UTERUS

The role of the epidermal-growth-factor receptor (EGFR) in cervical ca ncer is controversial, due to technical difficulties in localizing or in quantifying EGFR by homogenate assays or immunohistochemistry. Our autoradiographic approach, in combination with morphometry, allowed ce ll-type-specific quantification of EGFR, leading to the following obse rvations: (i) In normal cervical epithelium, EGFR levels per cell were high in non-dividing squamous cells of the upper layers of normal epi thelium, where a mitogenic function of these EGFRs can be excluded, (i i) In contrast to earlier findings in tissue homogenates, but consiste nt with our observation in normal cervical epithelium that cells of th e proliferating strata (basal and parabasal cells) express intermediat e and comparatively reduced levels of EGFR per cell, cervical cancers displayed a significant reduction both of specific EGF binding and of EGFR levels per cell as compared with normal epithelium. (iii) A signi ficant negative correlation of cell density and EGFR number per cell w as obtained, In normal cervical epithelium, cervical intra-epithelial neoplasia and invasive cervical cancer (p = 0.002). This negative corr elation was most evident in normal epithelium, where large changes of cell density occur within one slide (p < 0.001), (iv) Specific EGF-bin ding was also significantly reduced in endometrial cancers when compar ed with normal endometrium. It is proposed that in uterine tissues low or intermediate levels of EGFR do not exclude their function as media tors of cell proliferation. (C) 1998 Wiley-Liss, Inc.