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Syndecan-1表达在伴远处转移的浸润性乳腺癌中的临床/预后意义及其与肿瘤免疫的相关性

Clinical/prognostic significance of Syndecan-1 expression in invasive breast carcinoma with distant metastasis and its correlation with tumor immunity.

作者信息

Wang Huan, Zhang Yu, Yang Ziqi, Jiang Yong, Wu Lixue, Wang Rui, Zhang Zhang

机构信息

Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Pathology, Langzhong People's Hospital, Langzhong, Sichuan, China.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Pathol Res Pract. 2023 Oct;250:154787. doi: 10.1016/j.prp.2023.154787. Epub 2023 Aug 28.

DOI:10.1016/j.prp.2023.154787
PMID:37678063
Abstract

OBJECTIVE

Breast Cancer (BC) is the most common malignant tumor for women in the world. 90% of BC-associated deaths are attributed to distant metastasis (DM). Therefore, there is an urgent need for a novel molecular target for the treatment of distant metastatic breast cancer (DMBC). Syndecan-1 (SDC-1) is a cell surface heparan sulfate proteoglycan (HSPG). This study aims to study the expression patterns of SDC-1 in invasive breast carcinoma (IBC) with DM and to analyze its relationship with different clinicopathologic features, stromal tumor infiltrating lymphocytes (sTILs) status and the clinical outcomes.

METHODS

A total of 50 DM breast cancer and 100 non-distant metastasis (non-DM) breast cancer patients in West China Hospital, Sichuan University from January 1, 2011 to December 31, 2011 were collected. Immunohistochemical (IHC) method was used to detect the expression of SDC-1, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 in 150 specimens of patients with IBC. STILs were used to evaluate immune cells in the stromal tissue within the tumor. Various clinicopathologic characteristics were retrospectively analyzed, and follow-up information were collected for prognosis analyses. The expression pattern difference of SDC-1 in the DM group and the non-DM group and its correlation with clinicopathologic characteristics of IBC were analyzed.

RESULTS

Compared with the non-DM group, SDC-1 had higher cytoplasmic (90.0%) and stromal diffuse (70.0%) expressions and lower stromal peritumoral (18.0%) expression in the DM group. SDC-1 cytoplasmic expression was significantly associated with HER2-positive and high Ki-67 index in DM group, and with high histological grade and lymph node (LN) metastasis in non-DM group (P < 0.05). Compared with the non-DM group, the membranous expression of SDC-1 in the DM group was related to higher histological grade and T stage, higher frequency of LN involvement. Meanwhile, the expression pattern of SDC-1 in tumor stroma was associated with sTILs status (P < 0.05). The different combinations of SDC-1 staining patterns were correlated with clinicopathological features, biomarkers and sTILs status between DM group and non-DM group.There was no significant difference in overall survival between DMBC with different expression patterns of SDC-1.

CONCLUSION

The cytoplasmic and stromal expressions of SDC-1 in the primary lesion of IBC are closely associated with DM, and the stromal expression of SDC-1 is correlated with tumor immune microenvironment. SDC-1 is expected to be a potential new marker for predicting the risk of DM in IBC.

摘要

目的

乳腺癌(BC)是全球女性中最常见的恶性肿瘤。90%的乳腺癌相关死亡归因于远处转移(DM)。因此,迫切需要一种用于治疗远处转移性乳腺癌(DMBC)的新型分子靶点。Syndecan-1(SDC-1)是一种细胞表面硫酸乙酰肝素蛋白聚糖(HSPG)。本研究旨在探讨SDC-1在伴有DM的浸润性乳腺癌(IBC)中的表达模式,并分析其与不同临床病理特征、基质肿瘤浸润淋巴细胞(sTILs)状态及临床结局的关系。

方法

收集2011年1月1日至2011年12月31日在四川大学华西医院就诊的50例DM乳腺癌患者和100例非远处转移(非DM)乳腺癌患者。采用免疫组织化学(IHC)方法检测150例IBC患者标本中SDC-1、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)和Ki-67的表达。用sTILs评估肿瘤内基质组织中的免疫细胞。回顾性分析各种临床病理特征,并收集随访信息进行预后分析。分析DM组和非DM组中SDC-1的表达模式差异及其与IBC临床病理特征的相关性。

结果

与非DM组相比,DM组中SDC-1的细胞质表达较高(90.0%)、基质弥漫性表达较高(70.0%),而基质肿瘤周围表达较低(18.0%)。DM组中SDC-1的细胞质表达与HER2阳性和高Ki-67指数显著相关,在非DM组中与高组织学分级和淋巴结(LN)转移相关(P<0.05)。与非DM组相比,DM组中SDC-1的膜性表达与较高的组织学分级和T分期、较高的LN受累频率相关。同时,SDC-1在肿瘤基质中的表达模式与sTILs状态相关(P<0.05)。DM组和非DM组中SDC-1染色模式的不同组合与临床病理特征、生物标志物和sTILs状态相关。SDC-1表达模式不同的DMBC患者总生存期无显著差异。

结论

IBC原发灶中SDC-1的细胞质和基质表达与DM密切相关,SDC-1的基质表达与肿瘤免疫微环境相关。SDC-1有望成为预测IBC中DM风险的潜在新标志物。

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