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Abstract：
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.
OBJECTIVE: 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).
CONCLUSIONS: 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.
OBJECTIVE: 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).
CONCLUSIONS: 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.
摘要：
背景：幽门螺杆菌的影响(H.pylori）感染和胃癌（GC）对肿瘤浸润淋巴细胞（TIL）水平的特征尚未得到广泛研究。为了获得全面的信息，必须分析浸润免疫细胞亚型以及生存。
目的：为了确定错配修复缺陷（dMMR）的发生率，GC中HER2状态和幽门螺杆菌感染及其与TIL水平的关系。
方法：包含503例切除的GC肿瘤的样本，并根据国际TIL工作组的建议评估TIL水平，并评估肿瘤内（IT），基质（ST）和侵入性边界（IB）区室。CD3，CD8和CD163免疫细胞的密度，通过免疫组织化学（IHC）确定dMMR和HER2状态。通过常规组织学和定量PCR(qPCR)对一部分样品中的幽门螺杆菌感染进行评估。
结果：dMMR占34.4％，5％的样品中HER2+和55.7％的幽门螺杆菌阳性。高IT-TIL与3级相关(P=0.038),而ST-TIL为1级（P<0.001），肠组织学（P<0.001）和无复发（P=0.003）。dMMR与ST（P=0.019）和IB（P=0.01）隔室中的高TIL水平相关，和ST-CD3（P=0.049）和ST-CD8（P=0.05）密度。HER2-与高IT-CD8相关(P=0.009)。通过常规组织学评估时，幽门螺杆菌阴性与高IT-TIL水平相关（P=0.009），通过qPCR评估时，3个隔室中的TIL水平较高（P=0.002-0.047），IT和ST隔室中的CD8密度较高（P=0.001）。较长的总生存期与低IT-CD163（P=0.003）和CD8/CD3（IT中P=0.001，ST中P=0.002）和高IT-CD3（P=0.021）有关，ST-CD3(P=0.003)和CD3/CD163(P=0.002)。
结论：TIL水平与dMMR和幽门螺杆菌阴性相关。低CD8/CD3和高CD163/CD3与较低的复发和较长的生存期相关。
目的：为了确定错配修复缺陷（dMMR）的发生率，GC中HER2状态和幽门螺杆菌感染及其与TIL水平的关系。
方法：包含503例切除的GC肿瘤的样本，并根据国际TIL工作组的建议评估TIL水平，并评估肿瘤内（IT），基质（ST）和侵入性边界（IB）区室。CD3，CD8和CD163免疫细胞的密度，通过免疫组织化学（IHC）确定dMMR和HER2状态。通过常规组织学和定量PCR(qPCR)对一部分样品中的幽门螺杆菌感染进行评估。
结果：dMMR占34.4％，5％的样品中HER2+和55.7％的幽门螺杆菌阳性。高IT-TIL与3级相关(P=0.038),而ST-TIL为1级（P<0.001），肠组织学（P<0.001）和无复发（P=0.003）。dMMR与ST（P=0.019）和IB（P=0.01）隔室中的高TIL水平相关，和ST-CD3（P=0.049）和ST-CD8（P=0.05）密度。HER2-与高IT-CD8相关(P=0.009)。通过常规组织学评估时，幽门螺杆菌阴性与高IT-TIL水平相关（P=0.009），通过qPCR评估时，3个隔室中的TIL水平较高（P=0.002-0.047），IT和ST隔室中的CD8密度较高（P=0.001）。较长的总生存期与低IT-CD163（P=0.003）和CD8/CD3（IT中P=0.001，ST中P=0.002）和高IT-CD3（P=0.021）有关，ST-CD3(P=0.003)和CD3/CD163(P=0.002)。
结论：TIL水平与dMMR和幽门螺杆菌阴性相关。低CD8/CD3和高CD163/CD3与较低的复发和较长的生存期相关。
