Department of Immunology, Graduate Program in Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Clin Breast Cancer. 2017 Oct;17(6):441-452.e2. doi: 10.1016/j.clbc.2017.04.007. Epub 2017 Apr 21.
The influence of cancer-associated fibroblasts (CAFs) and high mobility group box 1 (HMGB1) has been recognized in several cancers, although their roles in breast cancer are unclear. The present study aimed to determine the levels and prognostic significance of α-smooth muscle actin-positive (ASMA) CAFs, plus HMGB1 and receptor for advanced glycation end products (RAGE) in cancer cells.
A total of 127 breast samples, including 96 malignant and 31 benign, were examined for ASMA, HMGB1, and RAGE by immunohistochemistry. The χ test and Fisher's exact test were used to test the association of each protein with clinicopathologic parameters. The Kaplan-Meier method or log-rank test and Cox regression were used for survival analysis.
ASMA fibroblast infiltration was significantly increased in the tumor stroma compared with that in benign breast tissue. The levels of cytoplasmic HMGB1 and RAGE were significantly greater in the breast cancer tissue than in the benign breast tissues. High ASMA expression correlated significantly with large tumor size, clinical stage III-IV, and angiolymphatic and perinodal invasion. In contrast, increased cytoplasmic HMGB1 correlated significantly with small tumor size, pT stage, early clinical stage, luminal subtype (but not triple-negative subtype), and estrogen receptor and progesterone receptor expression. The levels of ASMA (hazard ratio, 14.162; P = .010) and tumor cytoplasmic HMGB1 (hazard ratio, 0.221; P = .005) could serve as independent prognostic markers for metastatic relapse in breast cancer patients. The ASMA-high/HMGB1-low profile provided the most reliable prediction of metastatic relapse.
We present for the first time, to the best of our knowledge, the potential clinical implications of the combined assessment of ASMA fibroblasts and cytoplasmic HMGB1 in breast cancer.
癌症相关成纤维细胞（CAF）和高迁移率族蛋白 B1（HMGB1）的影响已在多种癌症中得到认可，尽管它们在乳腺癌中的作用尚不清楚。本研究旨在确定α-平滑肌肌动蛋白阳性（ASMA）CAF 以及 HMGB1 和晚期糖基化终产物受体（RAGE）在癌细胞中的水平及其预后意义。
共检测了 127 例乳腺样本，包括 96 例恶性和 31 例良性，通过免疫组织化学检测 ASMA、HMGB1 和 RAGE。使用卡方检验和 Fisher 确切检验检测每种蛋白与临床病理参数的相关性。采用 Kaplan-Meier 法或对数秩检验和 Cox 回归进行生存分析。
与良性乳腺组织相比，肿瘤基质中 ASMA 纤维浸润显著增加。乳腺癌组织细胞质中 HMGB1 和 RAGE 的水平明显高于良性乳腺组织。高 ASMA 表达与肿瘤体积大、临床分期 III-IV 级以及血管淋巴管和周围淋巴结侵犯显著相关。相反，细胞质 HMGB1 水平升高与肿瘤体积小、pT 分期、临床早期、腔型（而非三阴性型）以及雌激素受体和孕激素受体表达相关。ASMA（危险比，14.162；P=0.010）和肿瘤细胞质 HMGB1（危险比，0.221；P=0.005）的水平可作为乳腺癌患者转移性复发的独立预后标志物。ASMA 高/HMGB1 低的特征可提供转移性复发最可靠的预测。
据我们所知，这是首次提出联合评估乳腺癌中 ASMA 成纤维细胞和细胞质 HMGB1 的潜在临床意义。
