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

乳腺癌患者脑转移中基质PDGFR-β和α-SMA表达及临床意义分析

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作者:Md Rashedunnabi Akanda #, Eun-Jung Ahn #, Yeong Jin Kim, S M Abdus Salam, Myung-Giun Noh, Tae-Kyu Lee, Sung Sun Kim, Kyung-Hwa Lee, Kyung-Sub Moon

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-β), and alpha-smooth muscle actin (α-SMA) and the clinical and prognostic variables in BCBM patients.

Conclusions

Expression of PDGFR-β 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-β and α-SMA in the aggressive form of the TN subtype.

Methods

Immunohistochemistry (IHC) of the stromal expression of PDGFR-β and α-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-β and α-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-β, p = 0.009; α-SMA, p = 0.043) and BM solidity (p = 0.009 and p = 0.002, respectively). High PDGFR-β expression was significantly related to longer recurrence-free survival (RFS) (p = 0.011). TN molecular subtype and PDGFR-β 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-β 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-β and α-SMA in the aggressive form of the TN subtype.

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