Abstract P4-09-24: CD163 expression is associated with young age, triple negative subtype, and poor outcome in breast cancer
Authors: Ru Y , Hu PT , Kovatich AJ , Hooke JA , Liu J , Kvecher L , Fantacone-Campbell JL , Deyarmin B , Kovatich AW , Cammarata F , Rui H , Davidson-Moncada J , Shriver CD , Hu H 
Published: May 2016

BACKGROUND CD163 is a scavenger receptor specifically expressed by cells of monocyte/macrophage lineage. It is a biomarker in many clinical conditions, including coronary artery disease, anti-inflammatory response, and cancers. In breast cancer, high numbers of CD163-positive macrophages correlated with unfavorable outcome. Expression of CD163 in breast cancer was also related to early distant recurrence and poor survival. In this study we evaluated whether CD163 expression was associated with aggressive breast cancers from patients enrolled in the Clinical Breast Care Project (CBCP).

METHODS Patients were enrolled into the CBCP following IRB-approved, HIPAA-compliant protocols. The study focused on 129 invasive breast cancer samples with CD163 immunohistochemistry (IHC) results. Expression of CD163, ER, PR, HER2, and Ki67 were assayed by IHC. CD163 was positive if IHC&gt;0. ER and PR were positive if there was &gt;5% nuclear staining. HER2 was negative if IHC=0 or 1+ and positive if IHC=3+. For HER2 IHC=2+, HER2 was negative if FISH was &lt;1.8 and positive if FISH was &gt;2.2. Ki67 was positive if there was ≥15% nuclear staining. For subtyping, Luminal A (LA) was ER+/HER2-/Ki67-, Luminal B1 (LB1) was ER+/HER2-/Ki67+, Luminal B2 (LB2) was ER+/HER2+, Her2+ was ER-/PR-/HER2+, and triple negative (TN) was ER-/PR-/HER2-. Associations of CD163 IHC score with age, race, and IHC subtype were examined by Wilcoxon rank-sum tests and/or Fisher's exact tests. Prognoses of CD163 in overall survival (OS), disease specific survival (DSS), disease free survival (DFS), and recurrence were studied using univariable and multivariable Cox proportional hazards regression models. CD163 score, age, race, AJCC stage, and subtype were included in the multivariable model.

RESULTS CD163 IHC score displayed a significant negative correlation with age (R=-0.20, P=0.022). Patients with a CD163 score of 3+ were significantly younger than those with a score of 0 (P=0.019). CD163 score distributions were not statistically different between white and African American patients. CD163 scores of LA tumors were significantly lower than those of the tumors with all other subtypes except Her2+. Similarly, the CD163 scores of TN tumors were significantly higher than those of the tumors with all other subtypes but LB2. A higher CD163 score predicted worse DSS (HR=3.87 & P=0.0020 in univariable model; HR=4.21 & P=0.033 in multivariable model) and higher risk of recurrence (HR=2.85 & P=0.00016 in univariable model; HR=2.81 & P=0.012 in multivariable model).

CONCLUSION Higher CD163 expression in breast cancer was significantly associated with younger age, the TN subtype, worse DSS, and higher risk of recurrence. These results highlight CD163 as a prognostic marker for breast cancer.

The views expressed in this article are those of the author and do not reflect the official policy of the Department of Defense, or U.S. Government.

Citation Format: Ru Y, Hu PT, Kovatich AJ, Hooke JA, Liu J, Kvecher L, Fantacone-Campbell JL, Deyarmin B, Kovatich AW, Cammarata F, Rui H, Davidson-Moncada J, Shriver CD, Hu H. CD163 expression is associated with young age, triple negative subtype, and poor outcome in breast cancer. [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 P4-09-24.