Analysis of indoleamine 2-3 dioxygenase (IDO1) expression in breast cancer tissue by immunohistochemistry.
BACKGROUND
The immunosuppressive enzyme, indoleamine 2,3 dioxygenase (IDO), is overexpressed in many different tumor types including breast cancer. IDO inhibitors synergize with chemotherapy in breast cancer murine models. Characterizing IDO expression in breast cancer could define which patients receive IDO inhibitors. This study analyzed IDO protein expression in 203 breast cancer cases. The relationship between IDO, overall survival (OS), disease-specific survival (DSS), clinicopathologic, molecular, and immune tumor infiltrate factors was evaluated.


METHODS
Expression of IDO, estrogen receptor (ER), progesterone receptor (PR), human epithelial receptor 2, cytokeratin 5/6, epithelial growth factor receptor, phosphorylated AKT, neoangiogenesis, nitrogen oxide synthetase 2 (NOS2), cyclooxygenase 2 (COX2), FoxP3, CD8, and CD11b on archival breast cancer tissue sections was evaluated by immunohistochemistry. Associations between IDO and these markers were explored by a univariate and multivariate analysis. Survival was analyzed using Kaplan-Meier (OS) and Wilcoxon two-sample (DSS) tests.


RESULTS
IDO expression was higher in ER+ tumors compared to ER- tumors. IDO was lower in those with higher neoangiogenesis. OS was better in ER+ patients with high IDO expression. DSS was better in node-positive patients with high IDO expression. IDO activity positively correlates with NOS2. COX2 as positively correlated with IDO on univariate but not multivariate analysis. There was a trend toward greater numbers of CD11b+ cells in IDO-low tumors.


CONCLUSIONS
IDO protein expression is lower in ER- breast tumors with greater neoangiogenesis. Future clinical trials evaluating the synergy between IDO inhibitors and chemotherapy should take this finding into account and stratify for ER status in the trial design.
Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. hatem.soliman@moffitt.org
Hatem
H
Soliman
Bhupendra
B
Rawal
Jimmy
J
Fulp
Ji-Hyun
JH
Lee
Alexis
A
Lopez
Marylin M
MM
Bui
Farah
F
Khalil
Scott
S
Antonia
Harris G
HG
Yfantis
Dong H
DH
Lee
Tiffany H
TH
Dorsey
Stefan
S
Ambs
D001943:Breast Neoplasms / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D015233:Models, Statistical; D015999:Multivariate Analysis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051546:Cyclooxygenase 2