胃癌中幽门螺杆菌感染、错配修复、HER2 与 TIL（肿瘤浸润淋巴细胞）的关联

英文原题：Association between Helicobacter pylori infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer.

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Association between Helicobacter pylori infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer.

PubMed 2024/06/15（内容时间） World J Gastrointest Oncol Q3 · IF 2.7（JCR 2025）

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靶点：HER2 胃癌地区：其他

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研究概要

TIL 水平与 dMMR 和 H 相关。

中文摘要

背景

幽门螺杆菌（H. pylori）感染及胃癌（GC）特征对TIL（肿瘤浸润淋巴细胞）水平的影响尚未得到充分研究。需要分析浸润免疫细胞亚型和生存情况以获得全面信息。

目的

确定错配修复缺陷（dMMR）、HER2状态和H. pylori感染率，并分析其与GC中TIL水平的关系。

方法

纳入503份切除胃癌肿瘤样本，按国际TIL工作组建议评估TIL水平，分别分析瘤内、间质及浸润边缘区。通过免疫组化检测CD3、CD8、CD163免疫细胞密度及dMMR和HER2状态；在部分样本中采用常规组织学和定量PCR评估H. pylori感染。

结果

样本中dMMR占34.4%，HER2阳性占5%，H. pylori阳性占55.7%。瘤内TIL较高与3级分级相关（P=0.038）；间质TIL与1级分级（P<0.001）、肠型组织学（P<0.001）及无复发（P=0.003）相关。dMMR与间质区（P=0.019）和浸润边缘区（P=0.01）TIL较高，以及间质CD3（P=0.049）和CD8（P=0.05）密度相关。HER2阴性与瘤内CD8较高相关（P=0.009）。常规组织学检测H. pylori阴性与瘤内TIL高相关（P=0.009）；qPCR检测阴性则与三个区室TIL较高（P=0.002至0.047）及瘤内、间质CD8密度较高相关（P=0.001）。较长总生存期与较低瘤内CD163（P=0.003）和CD8/CD3比值（瘤内P=0.001，间质P=0.002），以及较高瘤内CD3（P=0.021）、间质CD3（P=0.003）和CD3/CD163比值（P=0.002）相关。

结论

TIL水平与dMMR及H. pylori阴性相关。较低CD8/CD3和较高CD163/CD3与较少复发及较长生存相关。

展开英文摘要原文

BACKGROUND

The influence of Helicobacter-pylori ( H. pylori ) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC.

METHODS

Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples.

RESULTS

dMMR was found in 34.4%, HER2+ in 5% and H. pylori -positive in 55.7% of samples. High IT-TIL was associated with grade-3 ( P = 0.038), while ST-TIL with grade-1 ( P < 0.001), intestinal-histology ( P < 0.001) and no-recurrence ( P = 0.003). dMMR was associated with high TIL levels in the ST ( P = 0.019) and IB ( P = 0.01) compartments, and ST-CD3 ( P = 0.049) and ST-CD8 ( P = 0.05) densities. HER2- was associated with high IT-CD8 ( P = 0.009). H. pylori -negative was associated with high IT-TIL levels ( P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments ( P = 0.002-0.047) and CD8 density in the IT and ST compartments ( P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 ( P = 0.003) and CD8/CD3 ( P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 ( P = 0.021), ST-CD3 ( P = 0.003) and CD3/CD163 ( P = 0.002).

CONCLUSION

TIL levels were related to dMMR and H. pylori -negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

论文信息

作者: Castaneda CA、Castillo M、Bernabe LA、Sanchez J、Fassan M、Tello K、Wistuba II、Chavez Passiuri I
第一作者单位: Faculty of Health Sciences, Universidad Cientifica del Sur, Lima 15038, Peru.
通讯作者单位: GECO PERU, Grupo de Estudios Clinicos Oncologicos del Peru, Lima 15038, Peru. ccastaneda@gecoperu.org.
期刊: World journal of gastrointestinal oncology2024 Jun 15

原文标识: PubMed 38994161　·　DOI 10.4251/wjgo.v16.i6.2487

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