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AR、SKP2、SOX10、PD-L1及TIL表达在三阴性乳腺癌中的意义

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  • 1.上海中医药大学附属曙光医院宝山分院病理科·上海市宝山区中西医结合医院病理科,上海 201900
    2.海军军医大学第一附属医院病理科,上海 200433
范德生 E-mail:hellen4099@126.com

收稿日期: 2023-11-07

  网络出版日期: 2024-07-04

基金资助

上海市宝山区医学重点专科项目(BSZK-2023-BP06);上海市宝山区卫生健康系统优秀学科带头人培养计划(BSWSYX-2024-4)

The clinicopathologic significance of AR, SKP2, SOX10, PD-L1 and TILs expression in triple-negative breast cancer

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  • 1. Department of Pathology, Baoshan Branch of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Hospital of Traditional Chinese and Western Medicine of Baoshan, Shanghai 201900, China
    2. Department of Pathology, First affiliated hospital, The Navy Military Medical University, Shanghai 200433,China

Received date: 2023-11-07

  Online published: 2024-07-04

摘要

目的:探索雄激素受体(androgen receptor,AR)、S期激酶相关蛋白2(S-phase kinase-associated protein 2,SKP2)、性别决定区Y相关的HMG盒含因子10(sry-related HMG box-containing factor 10,SOX10)、程序性死亡配体1(programmed death-ligand 1,PD-L1)及肿瘤浸润性淋巴细胞(tumor infiltrating lymphocyte,TIL)在三阴性乳腺癌(triple negative breast cancer,TNBC)表达与临床病理特征和预后的关系。方法:根据苏木精-伊红染色(hematoxylin-eosin, HE)染色切片评判109例TNBC瘤巢内TIL的比例,采用Leica Bond-Max全自动免疫组化仪检测TNBC组织中AR、SKP2、SOX10、PD-L1的表达。分析以上各生物指标与临床病理特征间的关系,并采用kaplan-Meier、Log-rank进行生存分析。结果:95例患者获得随访,中位随访时间为48个月,中位无病生存时间(disease-free survival, DFS)为42个月,中位总生存时间(overall survival, OS)48个月。在TNBC中,AR阳性表达与淋巴结转移阴性(P=0.009)、肿瘤最大径<2 cm(P=0.008)相关,TIL高表达与低级别TNBC相关(P=0.007),SKP2阳性表达与神经/脉管侵犯阳性(P=0.011)、高级别TNBC相关(P=0.002),SOX10阳性表达与淋巴结转移阳性(P=0.022)、高级别TNBC(P=0.005)相关,PD-L1阳性表达与淋巴结转移阳性(P=0.020)、神经/脉管侵犯阳性(P=0.006)、高级别TNBC(P=0.042)相关。生存分析显示,SKP2、SOX10阳性表达与更差的DFS(P=0.007、P<0.001)和OS(P=0.013、P<0.001)相关,TIL高表达与更好的DFS(P=0.016)及OS(P=0.004)相关。在生物表志物的联合表达中,AR+/SKP2-、AR+/SOX10-与更好的DFS(P=0.004、P<0.001)及OS(P=0.007、P=0.001)相关,SOX10+/低TIL、PD-L1+/低TIL与更差的DFS(P<0.001、P=0.008)及OS(P=0.001、P=0.002)相关,AR-/低TIL者具有更差的OS(P=0.014)。SKP2(HR=4.143,95%CI为1.578~10.875)、SOX10(HR=7.578,95%CI为2.067~27.782)的阳性表达是影响TNBC患者DFS的独立预后因子,SKP2(HR=3.758,95%CI为1.400~10.084)、SOX10(HR=5.131,95%CI为1.316~20.000)及TIL(HR=0.375,95%CI为0.154~0.917)的阳性表达是TNBC患者OS的独立预后因子(P均<0.05)。结论:在TNBC中,AR阳性、TIL高表达与具有更好预后的临床病理特征相关,SKP2、SOX10和PD-L1与具侵袭性的临床病理特征相关。SKP2、SOX10及TIL表达与TNBC预后相关,提示这些生物指标可能成为TNBC新的预后因子,同时它们也有可能成为潜在的治疗靶点。

本文引用格式

刘娟, 殷丽娟, 范德生 . AR、SKP2、SOX10、PD-L1及TIL表达在三阴性乳腺癌中的意义[J]. 诊断学理论与实践, 2024 , 23(02) : 162 -172 . DOI: 10.16150/j.1671-2870.2024.02.010

Abstract

Objective To explore the expression of androgen receptor (AR), S-phase kinase associated protein 2 (SKP2), Sry-related HMG box-containing factor 10 (SOX10), programmed death-ligand 1 (PD-L1) and tumor infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) and their relationships with clinical prognosis. Methods The proportion of TILs in 109 TNBCs was assessed on Hematoxylin-eosin stained sections ,and Leica Bond-Max automatic immunohistochemistry apparatus was used to detect the expressions of AR,SKP2,SOX10 and PD-L1 in TNBC tissue. The relationship between the above indicators and clinicopathological charactersitics was analyzed. Univariate survival analysis was performed by Kaplan-Meier, and survival by Log rank test. Multivariate survival analysis was performed by cox regression model. Results A total of 95 patients were followed-up with a median follow-up time of 48 months. For 95patients,the median disease-free survival (DFS) time was 42 months, and median overall survival (OS) time were 48 months. In TNBC, the expression of AR was associated with negative lymph node metastasis, maximum tumor diameter <2 cm. High expression of TILs was associated with low grade TNBC. The expression of SKP2 was associated with positive nerve/vasculature invasion and high grade TNBC. The expression of SOX10 was associated with high grade TNBC and positive lymph node metastasis. The expression of PD-L1 was associated with positive lymph node metastasis, positive nerve/vascular invasion, and high grade TNBC (all the P<0.05 as above). Survival analysis demonstrated that the positive expression of SKP2 or AR SOX10 was correlated with worse DFS (P=0.007、P<0.001) and OS (P=0.013、P<0.001), and patients with high expression of TILs showed better DFS (P=0.016) and OS (P=0.004). TNBC patients with AR+/SKP2- or AR+/SOX10- had better DFS (P=0.004、P<0.001) and OS (P=0.007、P<0.001), while those with SOX10+/low TILs or PD-L1+/low TILs had worse DFS (P=0.000、P=0.008) and OS (P=0.001、P=0.002), and AR-/low TILs had worse OS (P=0.014). Multivariate survival analysis showed positive expression SKP2 (HR=4.143, 95%CI 1.578-10.875), or SOX10 (HR=7.578, 95%CI 2.067-27.782) were independent prognostic factors for worse DFS, postive expression SKP2 (HR=3.758, 95%CI 1.400-10.084), or SOX10 (HR=5.131, 95%CI 1.316-20.000), were independent prognostic factors for worse OS (all the P<0.05 as above) and higher TILs(HR=0.375,95%CI 0.154-0.917) was independent prognostic factors for better OS(all the P<0.05 as above). Conclusions High expression of AR and TILs in TNBC indicate better prognosis, while SKP2, SOX10 and PD-L1 expression demonstrate more aggressive clinicopathological features in TNBC. The expression of SKP2, SOX10 and TILs in TNBC are associated with prognosis, suggesting that these indicators may serve as new prognostic factors and potential therapeutic targets in TNBC.

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