Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Gastric Cancer. 2024 Jan;27(1):86-101. doi: 10.1007/s10120-023-01446-6. Epub 2023 Nov 29.
Gastric adenocarcinoma is a highly heterogeneous malignancy with varying prognoses. In clinicopathological practice, we noticed a special tubular adenocarcinoma with diffuse neutrophils infiltrating (TADNI). However, the proportion and characteristics of TADNI remain unclear. This study aimed to evaluate the features of TADNI and explore probable treatments.
We divided 289 tubular adenocarcinoma cases into the TADNI and non-TADNI (nTADNI) groups by histological neutrophil quantity and performed immunohistochemistry of treatment-associated markers (CXCR1, CXCR2, PD-L1, CD8, HER2 and VEGFR2). Then we evaluated the clinical and morphological features in these cases. We also compared the value of histological features and peripheral blood neutrophil test. In addition, multiomics bioinformatic analyses were performed using the public datasets.
In our cohort, TADNI accounted for 10.4% of all tubular adenocarcinoma cases. These cases had worse prognoses (especially the neutrophils mainly outside the tubes) than nTADNI cases. The histological identification of TADNI had more prognostic value than peripheral blood neutrophils. CXCR1/CXCR2 expression was significantly high in TADNI group which indicated that CXCR1/CXCR2 inhibitors might be beneficial for TADNI patients. There were no significant differences in the expression of PD-L1, CD8, HER2 and VEGFR2. The analyses of TCGA data confirmed that TADNI cases had poorer prognoses and higher CXCR1/CXCR2 expression. Bioinformatic results also revealed molecular features (more hsa-mir-223 expression, fewer CD8-positive T cells and regulatory T cells, tighter communication between tumor cells' CXCR1/CXCR2 and neutrophils' CXCL5/CXCL8) of this type.
TADNI is a special morphological subtype with poorer prognoses and unique molecular characteristics, which might benefit from CXCR1/CXCR2 inhibitors.
胃腺癌是一种高度异质性的恶性肿瘤，具有不同的预后。在临床病理实践中，我们注意到一种特殊的管状腺癌，其弥漫性中性粒细胞浸润（TADNI）。然而，TADNI 的比例和特征尚不清楚。本研究旨在评估 TADNI 的特征，并探讨可能的治疗方法。
我们根据组织学中性粒细胞数量将 289 例管状腺癌病例分为 TADNI 组和非 TADNI（nTADNI）组，并对治疗相关标志物（CXCR1、CXCR2、PD-L1、CD8、HER2 和 VEGFR2）进行免疫组织化学染色。然后，我们评估了这些病例的临床和形态学特征。我们还比较了组织学特征和外周血中性粒细胞检测的价值。此外，还使用公共数据集进行了多组学生物信息学分析。
在我们的队列中，TADNI 占所有管状腺癌病例的 10.4%。这些病例的预后比 nTADNI 病例更差（尤其是中性粒细胞主要位于管外）。TADNI 的组织学鉴定比外周血中性粒细胞更有预后价值。TADNI 组中 CXCR1/CXCR2 的表达明显升高，表明 CXCR1/CXCR2 抑制剂可能对 TADNI 患者有益。PD-L1、CD8、HER2 和 VEGFR2 的表达无显著差异。TCGA 数据分析证实 TADNI 病例的预后较差，且 CXCR1/CXCR2 表达较高。生物信息学结果还揭示了这种类型的分子特征（hsa-mir-223 表达较多，CD8 阳性 T 细胞和调节性 T 细胞较少，肿瘤细胞的 CXCR1/CXCR2 与中性粒细胞的 CXCL5/CXCL8 之间的通讯更紧密）。
TADNI 是一种预后较差且具有独特分子特征的特殊形态亚型，可能受益于 CXCR1/CXCR2 抑制剂。
