Abstract
We aimed to evaluate the expression of amine oxidase proteins in breast cancer and their clinical implications. We performed immunohistochemical staining of amine oxidase proteins (LOX, lysyl oxidase, AOC3, amine oxidase, MAOA, monoamine oxidase A, MAOB, monoamine oxidase B). Based on their hormone receptors, such as estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 immunohistochemical staining, breast cancer was divided into four molecular subtypes: luminal A, luminal B, HER-2 type, and triple-negative breast cancer (TNBC). Luminal A was observed in 380 cases (49.4%), luminal B in 224 (29.1%), HER-2 type in 68 (8.8%), and TNBC in 98 (12.7%). Stromal AOC3, MAO-A, and MAO-B expression varied according to molecular subtypes. Stromal AOC3 expression was high in luminal B and HER-2 type and MAO-A expression was high in luminal A and luminal B (p < 0.001). MAO-B expression was higher in TNBC than in other subtypes (p = 0.020). LOX positivity was associated with high histological grade (p < 0.001) and high Ki-67 labeling index (LI) (p = 0.009), and stromal AOC3 positivity was associated with high histological grade (p = 0.001), high Ki-67 LI (p < 0.001), and HER-2 positivity (p = 0.002). MAO-A positivity was related to low histological grade (p < 0.001), ER positivity, PR positivity (p < 0.001), and low Ki-67 LI (p < 0.001). In univariate analysis, MAO-A positivity was related to short disease-free survival in HER-2 type (p = 0.013), AOC3 negativity was related to short disease-free survival and overall survival in ER-positive breast cancer, PR-positive breast cancer, HER-2-negative breast cancer, and lymph node metastasis. In conclusion, the expression of amine oxidase proteins varies depending on the molecular subtype of breast cancer. Stromal AOC3 expression was high in luminal B and HER-2 type, and MAO-A expression was high in luminal A and luminal B.
Highlights
Amine oxidase is an enzyme that catalyzes the oxidative cleavage of alkylamine into aldehydes and ammonia
High histological grade and Ki-67 labeling index (LI) were associated with triple-negative breast cancer (TNBC), high percentage of old-aged patients was associated with human epidermal growth factor receptor 2 (HER-2), and increased nodal metastasis was associated with luminal A (Table 1)
We investigated the expression of amine oxidase proteins based on molecular subtypes of breast cancer
Summary
Amine oxidase is an enzyme that catalyzes the oxidative cleavage of alkylamine into aldehydes and ammonia. Amine oxidase is divided into two groups according to cofactor: lysyl oxidase (LOX) and primary-amine oxidase, copper containing 2 and 3 (AOC2 and AOC3) that are proteins with copper as a cofactor, and monoamine oxidases (MAO), consisting of enzymes MAO-A and MAO-B, with falvin as a cofactor [1]. Amine oxidase participates in various metabolic pathways and is involved in cell differentiation, cell growth, wound healing, detoxification, and cell signaling [2]. Some amine oxidases have been reported to be involved in regulating cancers; LOX has played an important role in colorectal cancer cell dissemination in the bone marrow [3], and expression of AOC3 is associated with cancer prognosis in various tumors [4,5,6]. Amine oxidase can be expected to affect cancer biology
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