Oleksandr Mushii

Ukraine

The relationship between a-SMA expression and the clinical status of patients and features of the breast cancer collagen matrix.

Oleksandr Mushii1, Taras Zadvornyi1, Tetiana Burda1, Bazas Volodymyr2, Lukianova Nataliia1.
1. R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
2. Kyiv City Clinical Oncology Center, Kyiv, Ukraine

Abstract

Background

Tumor-associated fibroblasts (CAF) are one of the main components of the stromal microenvironment associated with the aggressiveness of the tumor process. At the same time, the relationship between a-SMA expression and the clinical status of patients and the features of the collagen matrix of breast cancer (BCa) has not been definitively clarified.

Methods

The study used histological postoperative material of 44 patients with stage I-II BCa who did not receive neoadjuvant therapy and were treated at the Kyiv Clinical Oncology Center. Studies of the expression of a-SMA, COL1A1, COL3A1, MMP-1, MMP-8, and MMP-13 were carried out immunohistochemically. A quantitative comparison of two independent groups was performed using the Mann Whitney U-test. Correlation analysis was performed using the Spearman test.

Results

A significant increase in the optical density of a-SMA (22.0% and 15.6%, respectively) was recorded in the tissue of poorly differentiated BCa and in patients with metastatic lesions of regional lymph nodes (p=0.008 and p=0.0005, respectively). Neoplasms of the luminal B molecular subtype of BCa were characterized by 15% (p=0.020), 18.9% (p=0.021) and 18.7% (p=0.027) higher indicators of the optical density of a-SMA compared to the tissue of luminal A, HER2/neu positive and triple negative BCa. When examining the relationship between the optical density of a-SMA and the collagen matrix components and tumor stroma remodeling markers expression levels, it was established that a-SMA indicators are directly correlated with the optical density of COL1A1 (r=0.357; p=0.022), COL3A1 (r=0.460; p=0.022). p=0.005), as well as the level of MMP-1 (r=0.354; p=0.020) and MMP-13 (r=0.382; p=0.010) in tissue.

Conclusions

The results obtained regarding the relationship between a-SMA expression and the clinical status of patients and the features of the collagen matrix of BCa confirm the participation of CAF in the remodeling of the stromal microenvironment, which determines the aggressiveness of the tumor process. This study was supported by the research programs Development and Validation of Complex Treatment Technology for Breast Cancer Patients of Young Age (0122U201203), Features of expression and methylation status of stromal microenvironment remodeling genes in breast cancer tissue (0123U102991), Stress-induced tumor microenvironment factors as risk drivers of breast cancer progression (0124U000078).