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肿瘤间质比、肿瘤间质成熟度、肿瘤浸润免疫细胞与食管胃结合部腺癌预后及新辅助治疗反应的关系

英文原题:Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma.

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Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma.

PubMed 2024/02/21(内容时间) Virchows Arch Q2 · IF 3(JCR 2025)

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中文摘要

准确预测预后和新辅助治疗反应对食管胃结合部腺癌(EGJA)患者至关重要。因此,我们旨在研究多种指标的预测能力,包括肿瘤间质比(TSR)、肿瘤间质成熟度(TSM),以及肿瘤浸润免疫细胞(TIICs)的密度和空间分布,如 T 细胞、B 细胞和肿瘤相关巨噬细胞(TAMs)。共纳入 695 例患者的切除和活检标本,来自国家癌症中心(NCC)和癌症基因组图谱(TCGA)队列。TSR 和 TSM 基于组织学评估进行评价。TIICs 在切除标本中通过免疫组织化学(IHC)染色后使用 QuPath 进行定量,而活检标本中则采用 Klintrup-Mäkinen(KM)分级评估 TIIC。间质水平高或间质不成熟的患者预后相对较差。

此外,肿瘤周边 CD8 + T 细胞计数高,以及肿瘤中心或肿瘤周边 CD68 + TAM 计数低,是独立的不良预后因素。

值得注意的是,结合 TSM 和 CD163 + TAMs 的组合模型在两个独立队列中均成为独立预后因素(分别为 HR 3.644,95% CI 1.341-9.900,p = 0.011 和 HR 1.891,95% CI 1.195-2.99,p = 0.006)。

此外,术前活检中间质水平高与新辅助治疗反应差相关(p < 0.05)。总之,我们的研究结果表明,TSR、TSM、CD8 + T 细胞、CD68 + TAMs 和 CD163 + TAMs 在一定程度上预测 EGJA 患者的预后。

值得注意的是,结合 TSM 和 CD163 + TAM 的组合模型可显著有助于预后分层。此外,术前活检标本中评估的高间质水平与新辅助治疗反应差相关。

展开英文摘要原文

Accurate predictions on prognosis and neoadjuvant therapy response are crucial for esophagogastric junction adenocarcinoma (EGJA) patients.

Therefore, we aimed to investigate the predictive abilities of several indicators, including tumor stroma ratio (TSR), tumor stroma maturity (TSM), and the density and spatial distribution of tumor-infiltrating immune cells (TIICs), such as T cells, B cells, and tumor-associated macrophages (TAMs). Resection and biopsy specimens of a total of 695 patients were included, obtained from the National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA) cohorts.

TSR and TSM were evaluated based on histological assessment. TIICs were quantified by QuPath following immunohistochemical (IHC) staining in resection specimens, while the Klintrup-Mäkinen (KM) grade was employed for evaluating TIIC in biopsy specimens. Patients with high stromal levels or immature stroma had relatively worse prognoses.

Furthermore, high CD8 + T cell count in the tumor periphery, as well as low CD68 + TAM count either in the tumor center or in the tumor periphery, was an independent favorable prognostic factor. Significantly, the combination model incorporating TSM and CD163 + TAMs emerged as an independent prognostic factor in both two independent cohorts (HR 3. 644, 95% CI 1. 341-9. 900, p = 0. 011 and HR 1. 891, 95% CI 1. 195-2. 99, p = 0. 006, respectively).

Additionally, high stromal levels in preoperative biopsies correlated with poor neoadjuvant therapy response (p < 0. 05).

In conclusion, our findings suggest that TSR, TSM, CD8 + T cell, CD68 + TAMs, and CD163 + TAMs predict the prognosis to some extent in patients with EGJA.

Notably, the combined model incorporating TSM and CD163 + TAM can contribute significantly to prognostic stratification.

Additionally, high stromal levels evaluated in preoperative biopsy specimens correlated with poor neoadjuvant therapy response.

论文信息

作者
Cheng N、Wang B、Xu J、Xue L、Ying J
第一作者单位
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China.China
通讯作者单位
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan, Chaoyang District, Beijing, 100021, China. jmying@cicams.ac.cn.China
期刊
Virchows Archiv : an international journal of pathology2025 Feb
原文标识
PubMed 38383941 · DOI 10.1007/s00428-024-03755-2