Increased immunostaining of fibulin-1, an estrogen-regulated protein in the stroma of human ovarian epithelial tumors.
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-alpha (ERalpha)-stained nuclei but was inversely correlated with the progesterone receptor. However, in cystadenomas and borderline tumors, both fibulin-1 and ERalpha 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.
Roger
P
P
INSERM U.148 and Department of Cell Biology, CHU de Montpellier-Hôpital Lapeyronie, France.
Pujol
P
P
Lucas
A
A
Baldet
P
P
Rochefort
H
H
D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000737:chemistry / Q000473:pathology; D018293:Cystadenoma, Serous / Q000737:chemistry / Q000473:pathology; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010051:Ovarian Neoplasms / Q000737:chemistry*; D010053:Ovary / Q000737:chemistry; D010534:Peritoneal Neoplasms / Q000556:secondary; D010865:Pilot Projects; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C060820:fibulin