Determination of the cellular retinoic-acid-binding protein in dysplastic epithelia of the cervix uteri, differentiated into apo and holo forms

Purpose: The appearance of the cervical mucosa is regulated by different fa ctors including retinoic acid. Hormone-dependent alteration of the cervix u teri mucosa is accompanied by a decrease or increase of cytoplasmatic retin oic-acid-binding protein (CRABP). To elucidate whether this hormone-depende nt alteration of CRABP is preserved in the case of neoplasms of the cervix uteri, we measured the level of total and apo-CRABP in normal and neoplasti cally transformed cervical cells. Methods: In a prospective pilot study, st andardised biopsies of normal epithelium and cervical intra-epithelial neop lasm grade 3 (CIN III) were taken from 24 patients. A newly developed metho d was used to determine the intra-epithelial level of apo- and total CRABP. Results: The concentration of total CRABP in normal squamous epithelium co mpared with that in intra-epithelial neoplasm grade 3 is very significantly lower in the CIN III areas (normal: 3.66 +/- 1.46 pmol/mg wet weight +/- S D CIN III 1.43 +/- 0.59 pmol/mg P < 0.01). In addition CRABP in the apo for m is lower in normal than in neoplastic epithelium (Wilcoxon test for paire d non-parametric values: P < 0.05; mean for all patients: normal: 1.65 + 0. 82 pmol/mg; CIN III: 1.14 +/- 023 pmol/mg). Conclusion: From our results we conclude that, in neoplastically transformed cells, the hormone-dependent CRABP cycle is interrupted. Whether this has consequences for the further d evelopment of the neoplastic cells has to be elucidated.