Abstract 3927: The presence of COX-2 and tumor-associated macrophages as a prognostic marker for invasive breast carcinoma patients

Abstract

Abstract Inflammation is an important mediator of tumor progression. The objective of this study was to assess whether the tissue localization of COX-2 and tumor-associated macrophages were associated with clinicopathological features of invasive carcinoma, including collagen deposition and patient survival outcome. A tumor microarray (TMA) of 371 biopsy specimens from patients with invasive breast carcinoma was analyzed for expression of high levels of COX-2, and the macrophage markers CD68 and CD163 in either the tumor nest (TN) or the tumor-associated stroma (TS). The study population for this TMA was female patients, 18 to 80 years of age with a median follow up of 8.4 years. Survival tables were calculated according to the Kaplan-Meier method. We found that elevated collagen deposition was associated with high stromal expression of COX-2 (P < 0.0001); however, the amount of collagen deposition was not a predictor for survival outcome. In order to better analyze patient data, samples were divided into quartiles based on their levels of COX-2 expression and/or macrophage infiltration. Tumor nests with high COX-2 expression had worse patient outcome (P = 0.011). One possible mechanism for this is COX-2 dependent recruitment of macrophages to the tumor microenvironment, supported by our finding of high infiltration of CD68+ macrophages in the TS, and CD163+ macrophages in both TN and TS. This recruitment of macrophages was associated with worse overall survival (OS). Furthermore, patient survival was worsened even more if macrophages expressed COX-2, suggesting positive amplification of COX-2 signaling via macrophage recruitment. This notion is further established by the finding of high presence of CD163+ macrophages in the TN as an independent prognostic factor as revealed by multivariate analysis (P < 0.0001, HR = 4.67). These results suggest that in invasive carcinoma the localization of inflammatory markers within the tumor are biomarkers for patient survival outcome. Therefore, we propose that these patients may benefit from therapy with a selective COX-2 inhibitor such as celecoxib. Citation Format: Karla Esbona, Sandeep Saha, Yanyao Yi, Menggang Yu, Kari Wisinski, Lee G. Wilke, Patricia J. Keely. The presence of COX-2 and tumor-associated macrophages as a prognostic marker for invasive breast carcinoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3927.