Retinoic acid receptors and retinoid binding proteins in endometrial adenocarcinoma: differential expression of cellular retinoid binding proteins in endometrioid tumours.

Retinoic acid is apparently required for the normal differentiation of reproductive epithelium. Cellular abnormalities in retinoid homeostasis could be a factor in the development of endometrial malignancy. We have thus investigated the expression of nuclear retinoic acid receptors (RARs and RXRs) and cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) in endometrial adenocarcinoma of the endometrioid histological subtype. Ten grade I, II grade 2 and 10 grade 3 tumour samples, as well as 4 samples of severe atypical precancerous endometrial hyperplasia, were studied. No significant difference in expression of RAR-beta was detected in tumour samples compared with normal epithelial cells. RAR-gamma was significantly elevated in grade 1 and 2 carcinomas, but this may be due to greater stromal cell involvement in these lower grade tumours. There was significant elevation of CRBP I mRNA in tumour samples. Furthermore, although undetectable in normal endometrial epithelium, CRABP I was expressed in 3/II grade 2 and 9/10 grade 3 carcinomas, with expression being significantly higher where the primary tumour had invaded more than 50% of the total myometrial thickness. Analysis of 2 epithelial-like endometrial adenocarcinoma cell lines supported the idea that CRABP I expression is characteristic of poorly differentiated endometrial adenocarcinoma. Our data suggest that alterations in mechanisms of retinoid homeostasis are a feature of endometrial adenocarcinoma and may contribute to the severity of disease.