The Change And Significance Of Indoleamine2,3-dioxygenase In Locally Advanced Breast Cancer Treatment

Objective:the aim of this study was to investigate the expression in local tumor tissue and the systemic activity of indoleamine2,3-dioxygenase (IDO) in locally advanced breast cancer, pre-and post-neochemotherapy and operation, then to seek the relationship between them. The effect of chemotherapy and operation on IDO-mediated metabolism of tryptophan was observed. The correlation between pathological response to chemotherapy, the systemic activity and expression in local tissue of IDO were explored via combination with clinicalpathological data.Methods:1.40cases locally advanced breast cancer patients (T3-4N0-1or T0-4N2-3) registed in Tianjin cancer hospital from January2011to October2012, were implemented needle aspiration biopsy to confirm the diagnoses and the specimens were obtained. All the patients were administrated2cycle neochemotherapy of TEC/TE. After estimating the chemotherapy efficiency,32cases with chemotherapy response were underwent surgery, specimens were obtained. Immunohistochemistry was used to detect IDO expression in tumor tissue pre-and post-chemotherapy.2.32cases locally advanced breast cancer patients were phlebotomized3ml the day before chemotherapy, the14th day after chemotherapy and7th day after operation. The serum was separated. High performance liquid chromatography (HPLC) was used to detect the concentrations of tryptophan (Trp) and kynurenine (Kyn), and the systemic activities of IDO (Trp/Kyn) were calculated.Results:1. Immunohistochemistry results showed that the rate of IDO over-expression in tumor tissue of30cases (2cases with a spot of tumor tissue post-chemotherapy) locally advanced breast cancer patients before chemotherapy [66.67%(20/30)] was higher [36.67%(11/30)](P<0.05). IDO expression in tumor for IDO positive patients descended after chemotherapy (P<0.05), and no difference for IDO negative patients pre-and post-chemotherapy. Patients with high expression of IDO before chemotherapy were inclined to have high expression after chemotherapy.2. HPLC analysis showed concentration of Trp in periphery blood descended after chemotherapy [(9.331±2.760)μg/ml] than before it [(10.716±1.738)μg/ml], and increased after operation [(10.793±1.888)μg/ml], which was much higher than pre-operation, with statistic difference (P<0.05). The Trp level in post-operation was slightly higher than post-chemotherapy without statistic difference (P>0.05). Concentration of Kyn descended post-chemotherapy [(0.359±0.103)μg/ml] than pre-chemotherapy [(0.407±0.148)μg/ml] without statistic difference (P>0.05), and was lowest after operation [(0.328±0.078)μg/ml] with statistic difference (P<0.05). Chemotherapy resulted in alteration of systemic IDO activity (P>0.05) which impaired by operation significantly (P<0.05).3. Patients with over-expression of IDO in tumor tissue pre-chemotherapy, accompanied with higher systemic IDO activity than those with low-expression. Patients with descending systemic IDO activity in post-chemotherapy, coupled with more reduction of IDO expression in tumor tissue (P<0.05).4. Alteration of Trp concentration between pre-chemotherapy and post-operation associated with pathological response to chemotherapy, with a correlation (P<0.05).Conclusion:1. Over-expression of IDO in tumor tissue accompanied with high systemic activity in locally advanced breast cancer patients. Expression of IDO descended after chemotherapy, associated with descended systemic activity (Kyn/Trp). Chemotherapy could affect the expression of IDO and the IDO expression changed in tumor tissue plays a key role to the change in systemic activity. Systemic IDO activity could indicate IDO expression level in local tumor tissue.2. Kyn and Trp concentration descended post-chemotherapy, and Kyn continued to descending after tumor removal, however, Trp level raised after operation, which suggested chemotherapy and surgery both impaired Trp degradation.3. Thus, alteration of Trp concentration post-surgery associated with pathological response to chemotherapy can be used to predict the long-term curative effect.