Analysis of stromal PDGFR-β and α-SMA expression and their clinical relevance in brain metastases of breast cancer patients

Background Breast cancer brain metastasis (BCBM) is a growing therapeutic challenge and clinical concern. Stromal cancer-associated fibroblasts (CAFs) are crucial factors in the modulation of tumorigeneses and metastases. Herein, we investigated the relationship between the expression of stromal CAF markers in metastatic sites, platelet-derived growth factor receptor-beta (PDGFR-beta), and alpha-smooth muscle actin (alpha-SMA) and the clinical and prognostic variables in BCBM patients. Methods Immunohistochemistry (IHC) of the stromal expression of PDGFR-beta and alpha-SMA was performed on 50 cases of surgically resected BCBM. The expression of the CAF markers was analyzed in the context of clinico-pathological characteristics. Results Expression of PDGFR-beta and alpha-SMA was lower in the triple-negative (TN) subtype than in other molecular subtypes (p = 0.073 and p = 0.016, respectively). And their expressions were related to a specific pattern of CAF distribution (PDGFR-beta, p = 0.009; alpha-SMA, p = 0.043) and BM solidity (p = 0.009 and p = 0.002, respectively). High PDGFR-beta expression was significantly related to longer recurrence-free survival (RFS) (p = 0.011). TN molecular subtype and PDGFR-beta expression were independent prognostic factors of recurrence-free survival (p = 0.029 and p = 0.030, respectively) and TN molecular subtype was an independent prognostic factor of overall survival (p < 0.001). Conclusions Expression of PDGFR-beta in the stroma of BM was associated with RFS in BCBM patients, and the clinical implication was uniquely linked to the low expression of PDGFR-beta and alpha-SMA in the aggressive form of the TN subtype.

Automated summary

This study investigated the relationship between the expression of stromal cancer-associated fibroblast (CAF) markers, platelet-derived growth factor receptor-beta (PDGFR-beta) and alpha-smooth muscle actin (alpha-SMA), and clinical and prognostic variables in breast cancer brain metastasis (BCBM) patients. The expression of PDGFR-beta and alpha-SMA was lower in the triple-negative (TN) subtype compared to other molecular subtypes. High PDGFR-beta expression was associated with longer recurrence-free survival (RFS). TN molecular subtype and PDGFR-beta expression were independent prognostic factors for both recurrence-free survival and overall survival.