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(American Journal of Pathology. 1998;153:1579-1588.)
© 1998 American Society for Investigative Pathology

Regular Articles

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

Pascal Roger* , Pascal Pujol* , Annick Lucas* , Pierre Baldet and Henri Rochefort*

From INSERM U.148 and Department of Cell Biology* and Department of Pathology, CHU de Montpellier-Hôpital Lapeyronie, Montpellier, France

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- (ER)-stained nuclei but was inversely correlated with the progesterone receptor. However, in cystadenomas and borderline tumors, both fibulin-1 and ER protein levels increased, in comparison with normal ovaries, suggesting an effect of estrogens in the early steps of tumorigenesis. This fibulin-1 overexpression, demonstrated in vivo in ovarian carcinomas, might be a useful indicator for predicting cancer risk and/or aggressiveness.

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