Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer.
BACKGROUND
Expression of estrogen-regulated genes has been considered as potential predictive markers for endocrine therapy. We focused on two insulin-like growth factor binding proteins (IGFBPs): IGFBP-4, which is an early-responsive estrogen-induced gene, and IGFBP-5, which is an estrogen-repressed gene. Investigation of IGFBP-4 and IGFBP-5 expression would provide important information for predicting prognosis and endocrine responsiveness.


METHODS
The levels of IGFBP-4 and IGFBP-5 mRNA expression in 162 human breast cancer tissues were analyzed using quantitative real-time reverse transcriptase-PCR. The association between IGFBP-4 and IGFBP-5 expression and clinicopathological factors was then analyzed.


RESULTS
The levels of IGFBP-4 and IGFBP-5 mRNA expression were positively correlated with estrogen receptor (ER) and progesterone receptor (PgR) status and were negatively correlated with HER2 overexpression. Patients with a high level of IGFBP-4 mRNA expression had better disease-free and overall survival than those with a low expression. Multivariate analysis showed that IGFBP-4 mRNA expression is an independent prognostic factor for disease-free survival. When analyzed in 116 patients with ER-positive breast cancer, patients whose tumor expressed higher levels of IGFBP-4 mRNA or lower levels of IGFBP-5 mRNA had better disease-free survival.


CONCLUSIONS
IGFBP-4 mRNA expression was an independent prognostic factor in breast cancer, and patients with ER-positive breast cancer whose tumor expressed higher levels of IGFBP-4 and lower levels of IGFBP-5 had a better prognosis than those without such findings.
Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Keiko
K
Mita
Zhenhuan
Z
Zhang
Yoshiaki
Y
Ando
Tatsuya
T
Toyama
Maho
M
Hamaguchi
Shunzo
S
Kobayashi
Shin-ichi
S
Hayashi
Yoshitaka
Y
Fujii
Hirotaka
H
Iwase
Hiroko
H
Yamashita
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone