Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes

BackgroundProgrammed cell death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable targets for specific immunotherapy. This study investigated the expression of PD-L1 in surgically resected stage I adenocarcinomas and correlated this with known major driver mutations and clinical outcomes.Materials and methodsOne hundred and sixty-three patients with surgically resected stage I adenocarcinomas were explored. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ⩾5% of tumour cells were scored as positive for PD-L1 overexpression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing and anaplastic lymphoma kinsase (ALK) by immunohistochemistry. The correlations of PD-L1 expression with major driver mutations and clinicopathologic parameters were analysed.ResultsThe overall frequency of PD-L1 overexpression was 39.9% (65/163). PD-L1 had higher positive results in tumours with higher grade differentiation and vascular invasion and PD-L1 expression was not associated with the expressions of EGFR, KRAS, BRAF and ALK. Multivariate analysis revealed that abnormal carcinoembryonic antigen (CEA) and higher grade of differentiation were risk factors for poor relapse-free survival (RFS) and PD-L1 expression correlated with better RFS. Advanced pathologic stage was the independent risk for poor overall survival (OS).ConclusionsThe PD-L1 expression can be used as a prognostic indicator predictive of RFS in patients with surgically resected stage I lung adenocarcinomas. There may be a possibility for immunotherapy targeting the PD-L1 pathway in patients with lung adenocarcinoma in the future.     

靶向高通量测序在非小细胞肺癌中的临床应用

  目的  对8种与非小细胞肺癌（non-small cell lung cancer,NSCLC）个性化治疗高度相关的驱动基因进行检测,分析基因变异与临床病理特征的关系。  方法  收集天津医科大学肿瘤医院2016年6月至2017年8月212例NSCLC患者样本,对EGFR、KRAS、BRAF、ALK、MET、ERBB2、ROS1、RET 8种基因进行高通量测序。  结果  8种基因中EGFR基因变异率高达52.8%,其次为KRAS（8.5%）、ALK（8.0%）、ERBB2（6.1%）、MET（3.8%）、BRAF（1.4%）、RET（0.9%）、ROS1（0.9%）,75%样本检出至少1个驱动基因变异,驱动基因变异间呈现强烈互斥。最常见的EGFR突变为19外显子缺失和L858R突变,EGFR T790M突变与前面两个突变位点伴随出现。19外显子缺失患者携带非EGFR T790M突变比例低于L858R突变患者携带非EGFR T790M突变比例（P=0.04）。15.2%EGFR突变伴EGFR扩增,携带EGFR扩增且EGFR突变率 > 40%患者比例高于无EGFR扩增且EGFR突变率 > 40%患者（P < 0.01）。女性、不吸烟、腺癌患者易发生EGFR特别是EGFR敏感突变（P < 0.01）。肺腺癌（P=0.013）、临床分期晚（P=0.048）、淋巴结转移（P=0.027）患者携带EGFR扩增比例高。男性（P=0.009）、左侧肺癌（P=0.048）,吸烟患者（P=0.037）KRAS突变发生率较高。携带非KRAS突变、ALK融合的患者更年轻（P=0.005,P=0.031）,而携带KRAS突变患者年龄较高（P=0.055）。  结论  高通量测序可同时高效检测NSCLC患者中8种与靶向治疗相关驱动基因的变异谱,为临床医生的个体化诊疗提供参考,以多基因为基础的高通量测序为NSCLC诊疗提供更多的可能性。      

肺癌驱动基因与非小细胞肺癌生存关系的相关性研究

目的探讨非小细胞肺癌驱动基因EGFR、KRAS、BRAF、PIK3CA、ALK、MET、HER-2、RET、ROS-1与患者预后相关性,寻找更有效防治分子靶标。方法利用Kaplan-Meier(KM)plotter在线数据库分析EGFR、KRAS、BRAF、PIK3CA、ALK、MET、HER-2、RET、ROS-1表达与非小细胞肺癌患者总生存期(overall survival OS),性别与吸烟状态等参数的相关性,并得出相应的危险比(Hazard ratio,HR)、95%置信区间(CI)和P值。结果研究结果显示:高表达EGFR、BRAF、MET、RET、ROS-1的患者有较好的OS。进一步引入吸烟状态和性别参数显示,BRAF、MET,PIK3CA、HER-2、ALK的表达与患者的吸烟状态存在相关性(P<0.05)。BRAF、MET、EGFR、ALK表达与OS的相关性存在性别差异(P<0.05)。结论各驱动基因在患者预后评判中既是独立因素,又相互作用,吸烟状态与性别也是决定患者预后的关键因素,提示临床治疗时要对患者进行综合的评判,要进行多基因的共同分析、多靶点的联合治疗才能使病人获得更大的收益。     

Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma

BackgroundProgrammed cell death-ligand 1 (PD-L1) is expressed in a subgroup of lung cancer that may benefit from immunotherapy. The interaction between PD-L1 expression and tumour infiltrating lymphocytes (TIL) remains poorly understood. This study investigated the expression of PD-L1 in surgically resected stage I pulmonary squamous cell carcinoma (SqCC) and correlated it with TILs in tumour microenvironments, common driver mutations, and clinical outcomes.Materials and methodsOne hundred and five patients with surgically resected stage I squamous cell carcinoma were examined. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ≥5% of tumour cells were scored as positive for PD-L1 expression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing, while anaplastic lymphoma kinase (ALK), phosphoinositide 3-kinase catalytic alpha (PI3KCA), and fibroblast growth factor receptor 1 (FGFR1) were analysed by immunohistochemistry. The correlations of PD-L1 expression with each subtype of TIL, driver mutations, clinicopathologic parameters, and clinical outcomes were analysed.ResultsThere was positive PD-L1 expression in 56.2% (59/105) of patients. PD-L1 expression was not associated with the common clinicopathologic features and mutations of EGFR, KRAS, BRAF, ALK, PI3KCA, and FGFR1. As regards TILs composition, tumour PD-L1 expression was significantly associated with increased tumour epithelial CD8+ T cells and stromal CD4+ T cells. Otherwise, PD-L1 (+) tumour cells were negatively correlated with PD-L1 (+) immune cells within tumour stroma. By multivariate analysis, tumour PD-L1 expression and increased CD4+ T cell infiltrations in the tumour stroma were independent predictors of better overall survival and had a trend of better disease-free survival.ConclusionsPD-L1 expression is associated with a favourable immune microenvironment in stage I pulmonary SqCC and correlates with better clinical outcome.     

PD-L1 is highly expressed in lung lymphoepithelioma-like carcinoma: A potential rationale for immunotherapy

ObjectivesProgrammed cell death-ligand 1 (PD-L1) and driver mutations are found in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung are unclear.Materials and methodsSixty-six patients with pulmonary LELCs were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Tumors with moderate-to-strong membrane staining in ≥5% of tumor cells were positive for PD-L1 overexpression. The presence of driver mutations in the genes for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were determined by immunohistochemistry. Correlations of PD-L1 expression and driver mutations with clinicopathologic parameters were analyzed.ResultsThe overall frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%, respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1 expression was not associated with driver mutations. Multivariate analysis revealed that smoking and advanced stage were independent risk factors for poor overall survival, whereas PD-L1 positivity was not significantly associated with patient outcome.ConclusionThere are high PD-L1 expression and infrequent driver mutations in LELCs compared with conventional NSCLCs. The high expression of PD-L1 in EBV and inflammation associated LELC may provide a rationale for immunotherapy in this subtype of lung cancer.     

PD-1/PD-L1 expression in non-small-cell lung cancer and its correlation with EGFR/KRAS mutations

This study was aimed to detect the correlation among EGFR/KRAS status and PD-1/PD-L1 expression in non-small-cell lung cancer (NSCLC) patients. PD-1 and PD-L1 expressions were detected by immunohistochemistry in 100 surgically resected lung adenocarcinoma tissues and were statistically correlated with clinicopathological characteristics including EGFR and KRAS statuses. Besides, the overall survival (OS) times were analyzed. There was a statistical significances between PD-1 expression in tumor and KRAS status (P = 0.043), with a higher mutation rate in with lower PD-1 expression patients. There was a statistical significance between PD-L1 expression in tumor and EGFR status (P = 0.012), with a higher mutation rate in patients with lower PD-L1 expression. The OS of patients with EGFR mutation was significantly longer than those without EGFR mutation. The OS of patients with lower PD-L1 in tumor was significantly longer than those with higher PD-L1 expression. We found negative associations between PD-L1 expression in tumor and mutated EGFR status, as well as between PD-1 expression in tumor and mutated KRAS status.     

Clinical characteristics associated with ALK rearrangements in never-smokers with pulmonary adenocarcinoma

Objectives

Anaplastic lymphoma kinase (ALK) rearrangement is a validated predictive marker to define patients with non-small cell lung cancer (NSCLC) who can benefit from selective ALK inhibitors. Therefore, accurate assessment of its prevalence and clinical characteristics is increasingly important in the treatment of NSCLC. Also, this ALK rearrangement was previously reported to be more common in patients with no smoking history or those with adenocarcinoma.

Patients and methods

Never-smokers with completely resected pulmonary adenocarcinoma were screened for ALK rearrangements using Nanostring's gene expression platform. Clinicopathologic data, such as information about epidermal growth factor receptor (EGFR) and KRAS mutation status were retrospectively reviewed.

Results

Of 231 tumors screened, 20 (9%) had an ALK rearrangement and all were confirmed to be positive with immunohistochemical and fluorescent in situ hybridization analysis. Of the tumors with available data on the EGFR/KRAS mutation status, EGFR and KRAS mutation rates were 64% (69/108) and 5% (5/102), respectively. Amongst the tumors that were free of EGFR and KRAS mutations, the proportion of ALK rearrangements reached up to 33%. At the time of data cut-off, total of 68 tumors were recurred. Although the recurrence rate was similar between the ALK-positive and negative groups (30% vs. 29%), there was a tendency for ALK-positive tumors to recur more frequently in the pleural space (15% vs. 5%). The five-year disease-free survival (61%) and overall survival rates (79%) in the ALK-positive group were similar to those in the ALK-negative group (51% and 83%, respectively). Even after excluding two patients treated with crizotinib after disease recurrence, overall survival was similar between the two groups.

Conclusion

In an NSCLC subpopulation based on smoking history, histology, and EGFR and KRAS mutation status, the prevalence of ALK rearrangements is considerably high. However, ALK rearrangement status itself has no prognostic relevance in patients with completely resected NSCLC.     

Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients

Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC). The relationship between LKB1 mutations and clinicopathological characteristics and other common oncogene mutations in NSCLC is inadequately described. In this study we evaluated tumour specimens from 310 patients with NSCLC including those with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma histologies. Tumours were obtained from patients of US (n=143) and Korean (n=167) origin and screened for LKB1, KRAS, BRAF, and EGFR mutations using RT-PCR-based SURVEYOR-WAVE method followed by Sanger sequencing. We detected mutations in the LKB1 gene in 34 tumours (11%). LKB1 mutation frequency was higher in NSCLC tumours of US origin (17%) compared with 5% in NSCLCs of Korean origin (P=0.001). They tended to occur more commonly in adenocarcinomas (13%) than in squamous cell carcinomas (5%) (P=0.066). LKB1 mutations associated with smoking history (P=0.007) and KRAS mutations (P=0.042) were almost mutually exclusive with EGFR mutations (P=0.002). The outcome of stages I and II NSCLC patients treated with surgery alone did not significantly differ based on LKB1 mutation status. Our study provides clinical and molecular characteristics of NSCLC, which harbour LKB1 mutations.     

Association between certain non–small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death‐ligand 1 inhibition

This study aimed to analyze the association between driver mutations and predictive markers for some anti–tumor agents in non–small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC‐related driver genes. In addition, the slides were tested for PD‐L1, excision repair cross‐complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and β‐tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild‐type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild‐type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower β‐tubulin III expression. In addition, wild‐type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD‐L1 high expression. As a pilot validation, 21 wild‐type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo‐regimen where targeted therapy has not been a routine option. Further validation is warranted.     

非小细胞肺癌EGFR、KRAS基因突变与RRM1、TUBB3 mRNA表达水平的相关性

目的:探讨非小细胞肺癌（NSCLC）EGFR、KRAS基因突变与核苷酸还原酶亚基M1（RRM1）、Ⅲ型β微管蛋白（TUBB3）mRNA表达水平的相关性及其临床意义。方法:69例NSCLC组织标本来自解放军空军总医院胸外科2010年6月至2014年10月手术中从肿瘤中心切取。使用xTAG-液相芯片法检测EGFR、KRAS基因突变,分支DNA-液相芯片法检测RRM1、TUBB3 mRNA表达水平。结果:在69例NSCLC组织样本中,28例为EGFR基因突变（40.6%,28/69）,13例为KRAS基因突变（18.8%,13/69）,EGFR基因突变与性别（P=0.005）、病理类型（P=0.036）、吸烟史（P=0.029）相关。KRAS基因突变与性别相关（P=0.007）。TUBB3 mRNA的表达水平与病理类型相关（P=0.008）,RRM1 mRNA的表达水平与患者各临床病理特征无关（P＞0.05）。EGFR基因突变与RRM1、TUBB3 mRNA表达水平无关（P＞0.05）,KRAS基因突变与RRM1 mRNA表达水平无关（P＞0.05）,KRAS突变型患者TUBB3 mRNA表达水平比KRAS野生型患者高（P＜0.05）。结论:在NSCLC患者中,EGFR及KRAS基因的突变状态对评估患者使用吉西他滨及抗微管类药物的疗效有重要意义,尤其在KRAS突变型NSCLC患者中,抗微管类化疗药物的疗效可能不佳,这有利于指导化疗药物方案的制定,促进NSCLC的个体化治疗。     

ALK基因状态与晚期肺腺癌患者一线培美曲塞化疗疗效的关系

背景与目的 间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)是非小细胞肺癌(non-small cell lung cancer,NSCLC)的重要驱动基因之一,多项研究显示培美曲塞在ALK阳性肺癌中的疗效存在争议.本研究旨在继续探索以培美曲塞为基础的化疗在ALK阳性和阴性肺腺癌患者中的疗效.方法 回顾性分析郑州大学第一附属医院2015年1月-2016年4月经组织病理学证实的98例表皮生长因子受体(epidermal growth factor receptor,EGFR)、鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)、鼠类肉瘤滤过性毒菌致癌同源体B1(V-rafmurine sarcoma viral oncogene homolog B1,BRAF)均为阴性的晚期肺腺癌患者的临床资料.分析ALK基因状态、临床特征、化疗疗效及无疾病进展生存期(progression-free survival,PFS)之间的关系.结果 98例患者均进行了ALK基因检测,ALK基因断裂融合34例(34.7%),未发生断裂融合64例(65.3%).全部患者均接受一线培美曲塞联合铂类的化疗,客观缓解率(objective response rate,ORR)为21.4%,疾病控制率(disease control rate,DCR)为84.7%.ALK阳性肺腺癌患者的ORR和DCR均高于阴性患者(41.2%vs 10.9%,χ2=23.389,P<0.001;91.2%vs 81.3%,χ2=4.153,P=0.042),差异有统计学意义.ALK基因状态与年龄、性别、吸烟史、临床分期均无明显关系.ALK阳性肺腺癌的中位PFS为7.1个月(95%CI:6.1-8.1),阴性4.7个月(95%CI:3.818-5.582),二者的PFS差异有统计学意义(χ2=13.269,P<0.001).Cox回归多因素分析显示:培美曲塞联合铂类化疗的PFS与性别、年龄、吸烟、分期、与铂类药物的种类均无明显关系,ALK基因断裂融合是PFS相关的唯一变量(HR=0.392,95%CI:0.243-0.634,P<0.001).结论 ALK阳性相比ALK阴性肺腺癌患者一线应用以培美曲塞为基础的化疗有更大的临床获益.     

非小细胞肺癌驱动基因检测及其与临床病理特征的相关性

目的:探讨非小细胞肺癌(NSCLC)驱动基因的变化情况及其与临床病理特征的相关性。方法:回顾性分析我院2016年01月至2020年07月NSCLC患者607例临床及病理学特征资料,采用扩增阻滞突变系统(ARMS)荧光PCR法检测EGFR突变,RT-PCR法检测ALK、ROS1基因融合,荧光原位杂交法（FISH）检测MET基因扩增。结果:607例NSCLC组织中325例(53.5%,325/607)检测到基因改变,分别为EGFR突变（45.5%,276/607）、ALK融合（5.1%,31/607）、ROS1融合（1.3%,8/607）和MET扩增（2.8%,17/607）,EGFR双位点突变15例（2.5%,15/607）,双驱动基因改变7例（1.2%,7/607）,其中EGFR突变与ALK融合阳性共存3例,EGFR突变与ROS1融合阳性共存2例,EGFR突变与MET扩增阳性共存2例。EGFR在女性、非吸烟、腺癌患者中突变率更高（P＜0.05）,EGFR突变更容易发生在以贴壁为主型、腺泡为主型、乳头为主型、微乳头为主型腺癌中（P＜0.05）;ALK融合多见于女性、年轻、非吸烟、实性为主型的腺癌患者（P＜0.05）;MET基因扩增在老年男性患者中发生率更高（P＜0.05）。结论:在NSCLC中EGFR突变率较高,驱动基因联合突变不容忽视,基因分型对临床治疗具有重要指导意义。     

The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs

Backgrounds

Recent clinical trials have shown that immune-checkpoint blockade yields remarkable response in a subset of non–small cell lung cancer (NSCLC) patients. However, few studies directly focus on the association between epidermal growth factor receptor (EGFR) mutational status and programmed cell death-ligand 1 (PD-L1) expression. We examined whether PD-L1 is related to clinicopathologic factors and prognosis in patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs).

Methods

One-hundred and seventy patients with advanced NSCLC were explored. Paraffin-embedded tumour sections were stained with PD-L1 antibody. EGFR mutation was examined by fluorescent quantitative polymerase chain reaction (PCR). The correlations between PD-L1 expression and EGFR status and survival parameters were analyzed.

Results

The overall frequency of PD-L1 over-expression was 65.9% (112/170). In lung adenocarcinoma, PD-L1 tended to be associated with mutant EGFR (PD-L1 overexpression in mutant and wild-type EGFR, 64/89 (71.9%) vs. 32/56 (57.1%), respectively; p=0.067). Subgroup analyses showed that high PD-L1 expression was associated with significantly shorter overall survival (OS) in EGFR wild-type patients (p=0.029) but not in EGFR mutant patients (p=0.932) treated with EGFR-TKIs. Even more, for EGFR mutant patients, higher expression of PD-L1 might only signal better outcome with TKIs.

Conclusions

High PD-L1 expression was likely to be associated with the presence of EGFR mutation in advanced lung adenocarcinoma. For EGFR wild-type patients, the PD-L1 over expression can be considered as a poor prognostic indicator of OS.     

Immunotherapy in the First-Line Setting in Wild-Type NSCLC

Treatment algorithms in the treatment of advanced non-small cell lung cancer (NSCLC) continue to evolve as new therapeutics show positive efficacy improvements. This review article summarizes the data for the use of immunotherapy for treatment in first-line stage IV NSCLC, organized by the following four sections: single-agent immunotherapy, immunotherapy and chemotherapy, dual immunotherapy, and dual immunotherapy and chemotherapy. The results are summarized and tabulated. Finally, application of the trial data is illustrated in four clinical scenarios depending on the programmed death-ligand 1 (PD-L1) expression levels. Single checkpoint inhibitors have become an easy and excellent treatment in patients whose tumors have high PD-L1 expression. Adding chemotherapy to immunotherapy benefits our patients. Immunotherapy, with or without chemotherapy, is now the standard of care in the first-line setting in patients without EGFR, ALK, or ROS driver mutations.     

肺癌驱动基因与PD-1/PD-L1信号通路相互作用在非小细胞肺癌发生发展中的研究进展

程序性死亡分子1(programmed death 1,PD-1)/程序性死亡分子1配体(programmed death 1 ligand,PD-L1)通路是免疫调节的重要通路,而这一通路在肿瘤组织中存在着异常激活,提示PD-1/PD-L1通路可能参与了肿瘤的免疫逃逸过程.肿瘤驱动基因在非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生发展中发挥着重要的作用,而对于肿瘤免疫逃逸的建立同样具有潜在的作用,这提示肿瘤驱动基因通路与PD-1/PD-L1通路可能存在相互作用.本文将对目前关于PD-L1与主要的肺癌驱动基因表皮生长因子受体基因(epidermal growth factor receptor,EGFR)、鼠类肉瘤病毒癌基因(Kirsten rate sarcoma viral oncogene homolog,KRAS)及棘皮微管样蛋白4-间变性淋巴瘤激酶融合基因(echinoderm microtubuleassociated protein-like 4-anaplastic lymphoma kinase,EML4-ALK)之间的关系及调控进行综述,总结肺癌驱动基因及PD-1/PD-L1通路相互作用在非小细胞肺癌发生发展中的作用.     

Expression of PD-1/PD-L1 in lung adenocarcinoma and its clinical significance

Objective This study aimed to investigate PD-1/PD-L1 expression in lung adenocarcinoma and its relationship with EGFR/KRAS mutation.Methods The expression levels of PD-1 and PD-L1 in lung adenocarcinoma were detected.Clinicopathological parameters were collected and followed up.The effects of PD-1 and PD-L1 expression on clinicopathological parameters and prognosis of patients with lung adenocarcinoma were statistically analyzed.Results PD-L1 and PD-1 were mainly located in the membrane and cytoplasm of tumor cells.The positive expression rates of PD-1 and PD-L1 were 53%and 40%,respectively.Positive PD-1 expression had a significant effect on the incidence of KRAS mutation(P<0.05),while PD-L1 expression significantly affected the incidence of EGFR mutation(P<0.05).Overexpression of PD-1 and PD-L1 had a significant negative effect on disease-free survival(DFS)in patients with lung adenocarcinoma(P<0.05)but had no significant effect on overall survival(P>0.05).EGFR gene mutation,high PD-1 expression,high PD-L1 expression,N stage,and AJCC stage were independent risk factors of DFS(P<0.05).Conclusion High PD-1/PD-L1 expression is closely related to the occurrence of lung adenocarcinoma and can be used as an independent factor to assess the prognosis of patients with lung adenocarcinoma.There were negative correlations between PD-L1 expression and EGFR mutation and between PD-1 expression and KRAS mutation.     

The Incidence of Brain Metastases in Stage IV ROS1-Rearranged Non–Small Cell Lung Cancer and Rate of Central Nervous System Progression on Crizotinib

Introduction

Central nervous system (CNS) metastases in lung cancer are a frequent cause of morbidity and mortality. There are conflicting data on the incidence of CNS metastases in stage IV ROS1-positive NSCLC and the rate of CNS progression during crizotinib therapy.

Immune Marker Profiling and Programmed Death Ligand 1 Expression Across NSCLC Mutations

Introduction

Programmed death 1/programmed death ligand 1 (PD-L1) axis inhibitors have been proven effective, especially in patients with tumors expressing PD-L1. Their clinical efficacy in patients with EGFR-activating mutations is still unclear, whereas KRAS mutations seem to be associated with good response.

非小细胞肺癌组织PD-L1的表达及其与临床因素的关系

目的:探索程序性死亡配体1 (programmed death-ligand 1,PD-L1)在中国非小细胞肺癌(non-small cell lung carcinoma,NSCLC)患者肿瘤组织中的表达水平及影响因素.方法:免疫组织化学法检测2008年4月至2014年8月天津医科大学肿瘤医院122例NSCLC初治患者肿瘤组织中PD-L1、PD-1和CD3+T细胞表达情况,采用x2和kruskal-wallis检验分析PD-L1表达在临床因素中分布差异性,用Person检验和Spearman检验分析PD-L1表达与EGFR基因型、CD3+T细胞数量及淋巴细胞PD-1表达的相关性,以及原发灶与淋巴结PD-L1表达相关性.结果:所有患者原发灶肿瘤细胞PD-L1表达百分比中位值1.5％(0～93.2％),PD-L1表达在TNM分期分布上有统计学差异(P =0.003),与TNM分期呈显著正相关(r=0.273,P=0.002),与性别、年龄、有无吸烟史、肿瘤最大径、病理类型、CEA水平分布无显著相关(P ＞0.05);PD-L1表达水平与CD3+T细胞数量、淋巴细胞PD-1表达水平无相关性,PD-L1表达阴性、低表达和高表达与表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变亦无显著相关(P ＞0.05);48例有淋巴结转移的NSCLC患者原发灶与相应转移淋巴结肿瘤细胞PD-L1表达水平无统计学相关性(P＞0.05).结论:NSCLC患者原发灶肿瘤细胞PD-L1表达在TNM分期分布上有差异,与CD3+T细胞数量、淋巴细胞PD-1表达水平、EGFR基因突变情况无相关性;原发灶与相应转移淋巴结之间肿瘤细胞PD-L1的表达亦没有相关性.     

EGFR、ALK和ROS1基因突变与肺腺癌病理分型的相关性研究

目的 分析EGFR、ALK和ROS1基因突变与非小细胞肺癌主要病理分型的相关性.方法 收集369例肺腺癌患者作为研究对象,采用ARMS荧光定量PCR法对样本进行EGFR、ALK和ROS1基因突变检测,按照2015年世界卫生组织(WHO)肺腺癌分型标准对其主要组织学分型确认,分析各基因突变与肺腺癌主要病理分型的相关性.结...