Abstract P2-08-25: Impact of kynurenine 3-monooxygenase expression on outcome in patients with triple-negative breast cancer undergone primary treatments
Authors: Wu C-Y , Chu P-Y , Wang W-L , Liu C-Y , Tseng L-M 
Published: May 2016

Background

Triple-negative breast cancer (TNBC), characterized by aggressive behavior and poor prognosis, represents an important clinical challenge because there is no well-established target therapy. Tryptophan-kynurenine metabolism in cancer is increasingly being recognized as a key factor that suppresses antitumor immune responses. Previous studies have focused on the expression and function of the rate-limiting enzyme indoleamine-2,3-dioxygenase in tumor cells, whereas the second step catabolic enzyme Kynurenine 3-monooxygenase (KMO) was rarely addressed in cancer. This study aimed to explore the clinical impact of KMO expression in patients with TNBC undergone primary treatments.

Methods

Primary tumors from 103 patients with TNBC who received surgical resection were enrolled for analysis. The expression of KMO and other clinicopathologic parameters, including tumor-infiltrating lymphocytes (TILs) and tumor expression of vascular endothelial growth factor (VEGF), was assessed semiquantitatively using immunohistochemistry-based scoring. Spearman rank correlation was used to examine the association between the expressions of KMO, TILs and VEGF. The clinical impact of KMO expression on survival was analyzed using Kaplan-Meier curve and Cox regression.

Results

The expression of KMO is significantly higher in breast tumor tissue, as compared with non-tumor tissue. In addition, a median of threefold higher KMO expression was observed in cancerous part comparing to non-cancerous part in resected specimens of TNBC, either in tumor/non-tumor paired or non-paired samples. The expression of KMO was negatively correlated with TILs (r = - 0.389, p &lt; 0.001) and positively correlated with VEGF expression (r = 0.344, p &lt; 0.001). Patients with higher KMO expression had a more advanced disease and demonstrated a trend toward poorer disease-free survival (DFS) (p = 0.065)(Table 1). Interestingly, an inverse distribution of TILs that contacted with tumor cells showing high KMO expression was observed in higher power field of microscopic examination. Moreover, patients with both higher expressions of KMO and VEGF had a poorer DFS, as compared with those without both higher KMO and VEGF expressions (hazard ratio, 1.52; 95% confidence interval, 1.17-1.97), after adjusted for tumor stage.

Clinical pathological factors in correlation with KMO expression High KMO H score (&gt;=60)Low KMO H score (&lt;60)P value N = 92N = 11 Age &gt;= 6032 (34.8)6 (54.5)0.321Primary tumor (T)  0.445126 (28.3)5 (45.5) 262 (67.4)5 (45.5) 3-44 (4.3)1 (9.1) Nodal status (N)  0.465050 (54.3)8 (72.7) 119 (20.7)2 (18.2) 2-323 (25.0)1 (9.1) Stage  0.01700 (0.0)1 (9.1) 116 (17.4)3 (27.3) 251 (55.4)6 (54.5) 325 (27.2)1 (9.1) Disease recurrence29 (31.5)0 (0.0)0.031Distant metastasis24 (26.4)0 (0.0)0.063Local recurrence15 (16.5)0 (0.0)0.361TIL (tumor-infiltrating lymphocyte) [median (range)]15 (1-90)40 (10-90)0.001VEGF [median, (range)]120 (0-300)45 (0-100)0.001presented as number (percentage)

Conclusion

Our data suggested KMO expression correlates with tumor infiltrating lymphocytes as well as VEGF expression, and may have a negative impact on outcome of patients with TNBC. The role of KMO in TNBC warrants further investigation.

(Grant supported by MOHW104-TD-B-111-02)

Citation Format: Wu C-Y, Chu P-Y, Wang W-L, Liu C-Y, Tseng L-M. Impact of kynurenine 3-monooxygenase expression on outcome in patients with triple-negative breast cancer undergone primary treatments. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-25.