Regular Articles
Increased Immunostaining of Fibulin-1, an Estrogen-Regulated Protein in the Stroma of Human Ovarian Epithelial Tumors

https://doi.org/10.1016/S0002-9440(10)65746-XGet rights and content

Fibulin-1, an extracellular matrix protein, is secreted by human ovarian metastatic cancer cell lines under estrogen stimulation. Fibulin-1 expression was quantified by immunohistochemistry and computer-aided image analysis in 44 human ovarian epithelial tumors and 14 normal ovaries. The fibulin-1 staining intensity in proximal stroma, close to the surface of epithelial cells and tumor cells, progressively increased from normal ovaries to serous carcinomas. In all lesions, excluding cystadenomas, fibulin-1 accumulation was higher in proximal stroma than in distant stroma. In situ hybridization demonstrated strong fibulin-1 gene expression in epithelial cells of serous ovarian carcinomas and some cysts. The weak expression of fibulin-1 RNA in some stromal cells of these tumors could not explain the strong fibulin-1 protein accumulation in tumor stroma, which was therefore mostly produced by tumor epithelial cells. In carcinomas, fibulin-1 staining was not correlated with the percentage of estrogen receptor-α (ERα)-stained nuclei but was inversely correlated with the progesterone receptor. However, in cystadenomas and borderline tumors, both fibulin-1 and ERα protein levels increased, in comparison with normal ovaries, suggesting an effect of estrogens in the early steps of tumorigenesis. This fibulin-1 overexpression, demonstratedin vivo in ovarian carcinomas, might be a useful indicator for predicting cancer risk and/or aggressiveness.

Cited by (0)

Supported by the Institut National de la Santé et de la Recherche Médicale, the Faculty of Medicine and University Hospital of Montpellier, the Association pour la Recherche sur le Cancer, the Groupement des Entreprises Française dans la Lutte Contre le Cancer, and the Ligue Nationale Contre le Cancer.

View Abstract