IGFBP2 and IGFBP3 protein expressions in human breast cancer: association with hormonal factors and obesity.
OBJECTIVE
The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics.


METHODS
IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, HER2 gene amplification, menopausal status, body mass index, and survival with IGF protein expression.


RESULTS
In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; P = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival.


CONCLUSIONS
According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight.
Probst-Hensch
Nicole M
NM
Institute of Social and Preventive Medicine, University of Zurich, Zurich. Nicole.Probst@unibas.ch
Steiner
Julia H B
JH
Schraml
Peter
P
Varga
Zsuzsanna
Z
Zürrer-Härdi
Ursina
U
Storz
Martina
M
Korol
Dimitri
D
Fehr
Mathias K
MK
Fink
Daniel
D
Pestalozzi
Bernhard C
BC
Lütolf
Urs M
UM
Theurillat
Jean-Philippe
JP
Moch
Holger
H
D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000378:metabolism*; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011374:Progesterone / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*
C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011960:Receptors, Estrogen; D011374:Progesterone; D007334:Insulin-Like Growth Factor I