Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, RI.
Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, RI.
Clin Breast Cancer. 2018 Jun;18(3):e373-e379. doi: 10.1016/j.clbc.2017.08.007. Epub 2017 Aug 19.
Expression of clusterin correlates with tumor progression and therapeutic response in several human malignancies, including breast cancer. However, its predictive value in the neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether clusterin expression in breast cancer correlated with clinical pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy (NAC).
We determined the clusterin expression pattern in 72 triple negative breast cancers (TNBC) treated with NAC before surgery. Clusterin expression was evaluated by immunohistochemistry and was correlated with pathologic characteristics and response to NAC using residual cancer burden score.
Immunohistochemistry analysis revealed a differential pattern of expression between tumor and stroma. Clusterin expression in the tumor associated stroma as opposed to expression by the neoplastic epithelium was significantly associated with neoadjuvant-treated TNBC. Low stromal clusterin, low stromal content, and high tumor-infiltrating lymphocytes were associated with a significantly greater likelihood of achieving a good pathologic response as reflected by lower residual cancer burden scores (P = .002, P = .003, and P = .001, respectively). Tumor and/or stromal clusterin expression were not associated with patient age, tumor histologic grade, stage, and lymph node status.
This study suggests a potential role for the assessment of stromal clusterin as a predictive biomarker for response of TNBC to neoadjuvant therapy. Further validation of this biomarker in a large study is needed.
在包括乳腺癌在内的几种人类恶性肿瘤中，簇集蛋白的表达与肿瘤进展和治疗反应相关。然而，其在乳腺癌新辅助治疗中的预测价值尚未得到探索。本探索性研究的目的是确定乳腺癌中簇集蛋白的表达是否与临床病理特征相关，以及其表达是否可预测新辅助化疗（NAC）的反应。
我们在 72 例接受 NAC 治疗的三阴性乳腺癌（TNBC）患者中确定了簇集蛋白的表达模式。通过免疫组织化学评估簇集蛋白的表达，并使用残留肿瘤负担评分来评估其与病理特征和 NAC 反应的相关性。
免疫组化分析显示肿瘤和基质之间存在不同的表达模式。与肿瘤上皮细胞表达相反，肿瘤相关基质中的簇集蛋白表达与新辅助治疗的 TNBC 显著相关。低基质簇集蛋白、低基质含量和高肿瘤浸润淋巴细胞与较低的残留肿瘤负担评分（分别为 P =.002、P =.003 和 P =.001）显著相关，提示获得良好病理反应的可能性更高。肿瘤和/或基质簇集蛋白表达与患者年龄、肿瘤组织学分级、分期和淋巴结状态无关。
本研究提示评估基质簇集蛋白作为预测 TNBC 对新辅助治疗反应的生物标志物具有潜在作用。需要在更大的研究中进一步验证该生物标志物。
