Investigation of IDO1 and TDO2 expression in breast tumors by immunohistochemistry and real time PCR

Breast cancer is the most common cancer among women and the second most common cause of death after lung cancer. It accounts for 24% of all female cancers and 14% of cancer-derived deaths. The Kynurenine pathway is an important metabolic pathway that is closely related to many diseases through the breakdown of tryptophan and the production of toxic Kynurenine metabolites. Indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (also known as TDO, TDO2) are the two main enzymes involved in the first step of the Kynurenine pathway. It is thought that cells expressing IDO create a state of immunological unresponsiveness to tumor-derived antigens. As part of the immune escape mechanisms, a large number of cancer cell types preferentially express IDO1 or TDO2, and in some cases both, haphazardly. It has been aimed to detect IDO1 and TDO2 by immunohistochemical and Real-Time method in breast cancer, and then to investigate the relationship of IDO1 and TDO2 with ER, PR, HER-2, Ki67 expression, molecular classification, histological subtypes and metastasis. Our study included 88 cases, 74 with breast carcinoma and 14 with normal breast tissue, who did not receive neoadjuvant treatment, that were sent to Dicle University Faculty of Medicine, Department of Pathology between January 2010 and December 2019. We examined IDO1 and TDO2 expressions by IHC and RT-PCR method. A significant difference was found between histological subtypes with IDO1 immunoreactivity and gene expression(p=0,005, p=0,009). IDO1 tends to be expressed mostly in cases with tumors and TDO2 tends to be expressed in both tumor and non-tumor cases. A statistically significant relationship was observed between IDO1 gene expression and age. In addition, IDO1 gene expression was observed at a higher rate in HER2 positive and triple negative cases compared to Luminal A and Luminal B cases. It has been described no significant difference between metastasis, ER, PR, HER2 and Ki67 and IDO1 and TDO2. There was no significant relationship of TDO2 with age, histological subtype, hormone receptor status and molecular class. 4 We think that IDO1 inhibitors might be suitable for the target patient group in the treatment selection of the significant increase in the tumor tissue of IDO and the higher positivity in the age, HER2 positive and triple negative cases compared to the other cases. Since TDO2 is expressed in both tumor tissue and normal breast tissue, we did not observe a significant result. Additional large series studies are needed to make any comments for TDO2.