胃癌中感染、错配修复、人表皮生长因子受体2（HER2）与肿瘤浸润淋巴细胞之间的关联
Association between infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer.
作者信息
Castaneda Carlos A, Castillo Miluska, Bernabe Luis A, Sanchez Joselyn, Fassan Matteo, Tello Katherine, Wistuba Ignacio Ivan, Chavez Passiuri Ivan, Ruiz Eloy, Sanchez Juvenal, Barreda Fernando, Valdivia Daniel, Bazan Yaqueline, Abad-Licham Milagros, Mengoa Claudio, Fuentes Hugo, Montenegro Paola, Poquioma Ebert, Alatrista Raul, Flores Claudio J, Taxa Luis
机构信息
Faculty of Health Sciences, Universidad Cientifica del Sur, Lima 15038, Peru.
GECO PERU, Grupo de Estudios Clinicos Oncologicos del Peru, Lima 15038, Peru.
出版信息
World J Gastrointest Oncol. 2024 Jun 15;16(6):2487-2503. doi: 10.4251/wjgo.v16.i6.2487.
BACKGROUND
The influence of () 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 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). 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 -positive in 55.7% of samples. High IT-TIL was associated with grade-3 ( = 0.038), while ST-TIL with grade-1 ( < 0.001), intestinal-histology ( < 0.001) and no-recurrence ( = 0.003). dMMR was associated with high TIL levels in the ST ( = 0.019) and IB ( = 0.01) compartments, and ST-CD3 ( = 0.049) and ST-CD8 ( = 0.05) densities. HER2- was associated with high IT-CD8 ( = 0.009). -negative was associated with high IT-TIL levels ( = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments ( = 0.002-0.047) and CD8 density in the IT and ST compartments ( = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 ( = 0.003) and CD8/CD3 ( = 0.001 in IT and = 0.002 in ST) and high IT-CD3 ( = 0.021), ST-CD3 ( = 0.003) and CD3/CD163 ( = 0.002).
CONCLUSION
TIL levels were related to dMMR and -negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
背景
（）感染及胃癌（GC）特征对肿瘤浸润淋巴细胞（TIL）水平的影响尚未得到广泛研究。分析浸润免疫细胞亚型及生存率对于获取全面信息很有必要。
目的
确定错配修复缺陷（dMMR）、人表皮生长因子受体2（HER2）状态及（）感染的发生率及其与GC中TIL水平的关联。
方法
纳入503例切除的GC肿瘤样本，按照国际TIL工作组的建议评估TIL水平，并对瘤内（IT）、基质（ST）和浸润边缘（IB）区域进行评估。通过免疫组织化学（IHC）测定CD3、CD8和CD163免疫细胞密度以及dMMR和HER2状态。在一部分样本中通过常规组织学和定量聚合酶链反应（qPCR）评估（）感染情况。
结果
34.4%的样本存在dMMR，5%为HER2阳性，55.7%为（）阳性。高IT-TIL与3级相关（P = 0.038），而ST-TIL与1级相关（P < 0.001）、肠型组织学相关（P < 0.001）且无复发相关（P = 0.003）。dMMR与ST（P = 0.019）和IB（P = 0.01）区域的高TIL水平以及ST-CD3（P = 0.049）和ST-CD8（P = 0.05）密度相关。HER2阴性与高IT-CD8相关（P = 0.009）。通过常规组织学评估时，（）阴性与高IT-TIL水平相关（P = 0.009），通过qPCR评估时，与3个区域的高TIL水平相关（P = 0.002 - 0.047）以及IT和ST区域的CD8密度相关（P = 0.001）。总生存期较长与低IT-CD163（P = 0.003）、CD8/CD3（IT中P = 0.001，ST中P = 0.002）以及高IT-CD3（P = 0.021）、ST-CD3（P = 0.003）和CD3/CD163（P = 0.002）相关。
结论
TIL水平与dMMR和（）阴性相关。低CD8/CD3和高CD163/CD3与较低的复发率和较长的生存期相关。
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