Level of Id-1 protein expression correlates with poor differentiation, enhanced malignant potential, and more aggressive clinical behavior of epithelial ovarian tumors.
OBJECTIVE
Id (inhibitor of differentiation/DNA binding) -1 is involved in neoangiogenesis, it antagonizes basic helix-loop-helix proteins, inhibits differentiation, and enhances cell proliferation. Aim of this study was to investigate Id-1 protein expression in epithelial ovarian tumors and its clinical relevance in ovarian cancer.


METHODS
We have investigated Id-1 expression by reverse transcription-PCR and Western blotting in ovarian cancer samples. On the basis of these results, Id-1 protein expression was determined by immunohistochemistry in 101 specimens of epithelial ovarian cancer, in 40 borderline tumors, and in 20 cystadenomas. In these cases, Id-1 expression was correlated with p21 expression, microvessel density, and survival.


RESULTS
By immunohistochemistry, detectable expression of Id-1 was found significantly more often in ovarian cancers (74.3%) than in borderline tumors (32.5%) and cystadenomas (0%; P < 0.0001, chi(2) test). Cancer samples with poor or moderate histological differentiation (G3/G2) showed significantly stronger Id-1 expression than cancer samples with high differentiation (G1; P = 0.021, Mann-Whitney test), and no association of Id-1 with p21 expression or microvessel density was found. In cancer samples strong or moderate expression of Id-1 was a strong predictor for shorter overall survival in uni- and multivariate analysis (P = 0.001, Cox-regression).


CONCLUSIONS
The level of Id-1 protein expression correlates with the malignant potential of ovarian tumors. In cancer samples, stronger Id-1 expression is associated with poor differentiation and more aggressive behavior of tumor cells, resulting in poor clinical outcome. Consequently, Id-1 inhibition in the future might be of benefit for patients with ovarian cancer.
Schindl
Monika
M
Institute of Clinical Pathology, University of Vienna, A-1090 Vienna, Austria.
Schoppmann
Sebastian F
SF
Ströbel
Thomas
T
Heinzl
Harald
H
Leisser
Christina
C
Horvat
Reinhard
R
Birner
Peter
P
D000704:Analysis of Variance; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D008833:Microcirculation / Q000473:pathology; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors