PDJ amplicon in triple negative breast cancer.
PDJ amplicon in triple negative breast cancer.
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DOI：
10.1038/s41598-023-27887-8
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发表时间：
2023-01-12
影响因子：
4.6
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中科院分区：
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靶向PD-L1、PD-L2和JAK 2的染色体9p24.1扩增（PDJ扩增子）存在于三阴性乳腺癌（TNBC）亚组中，并与不良临床结局相关。然而，PDJ+ TNBC的患病率在采用不同方法询问感兴趣样本的研究中差异很大。为了严格评估PDJ扩增子在TNBC中的患病率、其预后价值以及其是否通过化疗富集，我们询问了360个TNBC样品，包括来自在新辅助治疗环境中治疗的患者的74个手术切除，以及来自非裔美国妇女的31个病例和255个切除的非转移性病例的组织微阵列（TMA）。用靶向9p24.1 PDJ扩增子、9q24.3和9q34.1的3色荧光原位杂交（FISH）测定。平均PDJ信号> 4.5拷贝，并且PDJ/9 q24比值≥ 2和/或PDJ/9q34.1比值≥ 2的样本称为扩增（PDJ+）。相关性分析包括肿瘤浸润淋巴细胞（TIL）与TNBC中PDJ扩增子的相关性。此外，我们研究了PDJ+和PDJ− TNBC中PDJ扩增子的肿瘤内拷贝数。患者（n = 6）的匹配的新辅助治疗前后活检可用于评价治疗对PDJ状态的影响。我们的研究对TNBC中PDJ扩增子的患病率、分布和临床相关性进行了严格的分析。
Amplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1. Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 ≥ 2 and/or PDJ/9q34.1 ≥ 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ− TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC.
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