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间变性乳腺癌中干细胞特征、上皮-间充质转化、基底样表型、增殖和雄激素受体标志物的表达及其对预后的影响。

Expression of markers of stem cell characteristics, epithelial-mesenchymal transition, basal-like phenotype, proliferation, and androgen receptor in metaplastic breast cancer and their prognostic impact.

机构信息

Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland.

Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland.

出版信息

Acta Oncol. 2021 Sep;60(9):1233-1239. doi: 10.1080/0284186X.2021.1950927. Epub 2021 Jul 20.

Abstract

BACKGROUND

Metaplastic breast cancer (MpBC) is a heterogeneous subtype of invasive mammary carcinoma associated with epithelial-mesenchymal transition (EMT) and cancer stem cell characteristics. Data regarding prognostic markers and potentially actionable targets for therapy are still limited. The present study aimed to characterize the immunohistochemical landscape of this rare malignancy and to identify potential prognostic factors and targets for therapy.

MATERIAL AND METHODS

A total of 75 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for Ki-67 (MIB-1), epidermal growth factor receptor (EGFR), cytokeratin 5/6, vimentin, CD44, and androgen receptor (AR) and correlated their expression with clinicopathologic features and clinical outcomes. The -values for survival analyses were corrected for multiple testing (threshold 0.01).

RESULTS

Most tumors expressed CK5/6 (73%), EGFR (59%), CD44 (81%), and vimentin (87%). Eighty-nine percent had a high Ki-67 index. Eighty-four percent were classified as basal-like (CK 5/6 or EGFR positive). AR was expressed in 21% of the tumors. The basal-like phenotype was significantly ( = 0.009) associated with inferior disease-free (DFS) and breast-cancer-specific overall survival (BCOS) with borderline significance ( = 0.01). In addition, a low Ki-67 index was associated with improved DFS ( = 0.033) and BCOS ( = 0.03).

CONCLUSION

Most MpBCs express basal markers (CK5/6, EGFR), epithelial-mesenchymal transition marker vimentin, and the stem cell marker CD44. Expression of basal-like markers was significantly related to inferior DFS. All the 11 patients with a lack of expression of basal markers survived without relapse.

摘要

背景

化生性乳腺癌(MpBC)是一种具有上皮-间充质转化(EMT)和癌症干细胞特征的异质性浸润性乳腺导管癌。关于预测标志物和潜在治疗靶点的数据仍然有限。本研究旨在描述这种罕见恶性肿瘤的免疫组织化学特征,并确定潜在的预后因素和治疗靶点。

材料与方法

本研究共纳入了 15 年间诊断为 MpBC 的 75 例患者。我们对 Ki-67(MIB-1)、表皮生长因子受体(EGFR)、细胞角蛋白 5/6、波形蛋白、CD44 和雄激素受体(AR)进行免疫组织化学分析,并将其表达与临床病理特征和临床结果相关联。生存分析的 -值经多重检验校正(阈值 0.01)。

结果

大多数肿瘤表达 CK5/6(73%)、EGFR(59%)、CD44(81%)和波形蛋白(87%)。89%的肿瘤 Ki-67 指数较高。84%的肿瘤被归类为基底样(CK5/6 或 EGFR 阳性)。21%的肿瘤表达 AR。基底样表型与无病生存率(DFS)和乳腺癌特异性总生存率(BCOS)显著相关(=0.009),具有边界意义(=0.01)。此外,低 Ki-67 指数与改善 DFS(=0.033)和 BCOS(=0.03)相关。

结论

大多数 MpBC 表达基底标志物(CK5/6、EGFR)、上皮-间充质转化标志物波形蛋白和干细胞标志物 CD44。基底标志物的表达与DFS 显著相关。11 例缺乏基底标志物表达的患者均未复发且存活。

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