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.
AuthorsP Roger, P Pujol, A Lucas, P Baldet, H Rochefort
JournalThe American journal of pathology (Am J Pathol) Vol. 153 Issue 5 Pg. 1579-88 (Nov 1998) ISSN: 0002-9440 [Print] UNITED STATES
PMID9811350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Progesterone
  • fibulin
  • Calcium-Binding Proteins (analysis, genetics)
  • Cystadenocarcinoma, Serous (chemistry, pathology)
  • Cystadenoma, Serous (chemistry, pathology)
  • Disease Progression
  • Extracellular Matrix Proteins (analysis)
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Ovarian Neoplasms (chemistry)
  • Ovary (chemistry)
  • Peritoneal Neoplasms (secondary)
  • Pilot Projects
  • Prognosis
  • RNA, Messenger (analysis)
  • Receptors, Estrogen (analysis)
  • Receptors, Progesterone (analysis)
  • Stromal Cells (chemistry)

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