间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
肿瘤细胞治疗研究
英文原题:Molecular Classification of Gastric Cancer With Emphasis on PDL-1 Expression: The First Report From Iran.
Molecular Classification of Gastric Cancer With Emphasis on PDL-1 Expression: The First Report From Iran.
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胃癌是致死性肿瘤之一,患者尚无有效治疗,5 年生存率仍约为 25%–30%。寻找可靠生物标志物以实现早期诊断、靶向治疗和生存预测,是该领域的优先事项。
本研究旨在了解伊朗南部一组患者胃癌的分子分型。
在一项横断面研究中,选取 50 份组织量足以进行免疫组化(IHC)染色的胃癌标本。检测 HER2、错配修复基因 MLH1、MSH2、MSH6、PMS2 及 PD-L1,并比较标志物阳性频率与生存和结局的关系。 结果与结论:4 例(8.0%)检出错配修复缺陷(dMMR)。PMS2 缺失的 4 例中,1 例(25%)肿瘤细胞(TC)表达 PD-L1。然而,1 例 MLH1 缺失病例及 4 例 PMS2 缺失病例中的 3 例,其肿瘤细胞和TIL(肿瘤浸润淋巴细胞)均未检出 PD-L1,差异无统计学意义。50 例均表达 MSH2 和 MSH6,其中 24% 的病例肿瘤细胞表达 PD-L1,32% 的病例 TIL 表达 PD-L1。2 例(2/50,4.0%)HER2 阳性病例的肿瘤细胞和 TIL 均表达 PD-L1;在 HER2 阴性组中,肿瘤细胞 PD-L1 阳性率为 26.2%(11/42),TIL 阳性率为 28.6%(12/42)。HER2 阴性肿瘤细胞中的 PD-L1 表达率显著高于 HER2 阳性肿瘤细胞(P=0.033)。6 例(12.0%)HER2 免疫组化结果不确定,肿瘤细胞均未表达 PD-L1。自胃癌检出至死亡或随访终止的最短和最长生存时间分别为 1 个月和 87 个月。总生存期均值±标准差和中位数±标准差分别为 30.69±4.88 个月和 18±1.45 个月;1 年和 3 年生存率分别为 40% 和 24%。PD-L1 表达与生存无关,但与 Lauren 肠型及 HER2 阴性相关。肿瘤细胞或 TIL 中 PD-L1 阳性均不是胃癌的独立预后因素。
Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer.
In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran.
In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. RESULTS AND CONCLUSION: In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs ( P = .033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean SD and median SD of overall survival time were 30.69 4.88 and 18 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer.
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