肺癌患者的多原发恶性肿瘤

目的：总结肺癌患者多原发恶性肿瘤的诊断和治疗经验。方法：分析肺癌患者多原发恶性肿瘤４５例的临床病理资料,占同期手术病理证实１８３６例肺癌的２．５％。男３８例,女７例。多原发肺癌１６例,占０．９％,其中１５例为双原发癌,１例为三原发癌;肺癌与其他脏器恶性肿瘤２９例,占１．６％,其中２７例为双原发恶性肿瘤,２ 三原发癌。结果：多原发肺癌患者术后３和５年生存率为６０．０％（６／１０）和４４．４％（４／９     

The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic,Clinical and Radiologic Advances Since the 2004 Classification

The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to “pulmonary hamartoma,” (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and (c) PEComa, malignant, (12) introducing the entity pulmonary myxoid sarcoma with an EWSR1–CREB1 translocation, (13) adding the entities myoepithelioma and myoepithelial carcinomas, which can show EWSR1 gene rearrangements, (14) recognition of usefulness of WWTR1–CAMTA1 fusions in diagnosis of epithelioid hemangioendotheliomas, (15) adding Erdheim–Chester disease to the lymphoproliferative tumor, and (16) a group of tumors of ectopic origin to include germ cell tumors, intrapulmonary thymoma, melanoma and meningioma.     

High Prevalence of Concomitant Oncogene Mutations in Prospectively Identified Patients with ROS1-Positive Metastatic Lung Cancer

ObjectivesChromosomal rearrangements involving ROS1 define a rare entity of lung adenocarcinomas with exquisite sensitivity to molecularly targeted therapy. We report clinical outcomes and genomic findings of patients with ROS1-positive lung cancer who were prospectively identified within a multiplex biomarker profiling program at the West German Cancer Center.MethodsStandardized immunohistochemical (IHC) analysis, fluorescence in situ hybridization (FISH), and hotspot mutation analyses were performed in 1345 patients with advanced cancer, including 805 patients with metastatic lung adenocarcinoma. Clinical and epidemiological data were retrieved from the institutional database.ResultsROS1 positivity by IHC analysis was detected in 25 patients with lung cancer (4.8% of lung adenocarcinomas), including 13 patients (2.5%) with ROS1 FISH positivity with a cutoff of at least 15% of events. Of the ROS1 IHC analysis–positive cases, 36% presented with concomitant oncogenic driver mutations involving EGFR (six cases, five of which were clinically validated by response to EGFR-targeting agents), KRAS (two cases), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), and BRAF. Three cases initially classified as ROS1 FISH–negative passed the threshold of 15% positive events when repeat biopsies were analyzed at progression. The median overall survival of the ROS1-positive patients (104 months) was significantly superior to that of the 261 patients with EGFR/anaplastic lymphoma kinase/ROS1–negative lung adenocarcinoma (24.4 months, p = 0.044). Interestingly, the overall survival of the 13 ROS1-positive patients with lung cancer from initiation of pemetrexed-based chemotherapy was significantly prolonged when compared with that of 169 pemetrexed-treated patients with EGFR/anaplastic lymphoma kinase/ROS1–negative adenocarcinoma (p = 0.01).ConclusionsROS1-positive metastatic lung adenocarcinomas frequently harbor concomitant oncogenic driver mutations. Levels of ROS1 FISH–positive events are variable over time. This heterogeneity provides additional therapeutic options if discovered by multiplex biomarker testing and repeat biopsies.     

小细胞肺癌驱动基因研究进展

小细胞肺癌是一类具有高度侵袭性的肺恶性肿瘤,预后极差,近30年来,其治疗策略无明显进展。积极研究小细胞肺癌分子生物学特征,并筛选潜在驱动基因,有助于为小细胞肺癌开拓新的治疗途径,改善疾病预后。本文将对小细胞肺癌驱动基因研究相关进展进行综述。     

高表达p73 基因对肺腺癌细胞VEGF 、bFGF 表达抑制作用的研究

 目的 观察高表达的p73基因对肺腺癌细胞中VEGF、bFGF mRNA和蛋白表达水平的影响。方法 将p73基因以脂质体法转染A549细胞、H1299细胞，G418筛选阳性细胞克隆．采用RT-PCR半定量法检测转染前后VEGF、bFGF mRNA的表达水平，Western-blot半定量法检测蛋白表达水平。结果 转染p73基因后，A549细胞、H1299细胞中VEGF、bFGF mRNA和蛋白表达水平均下降，较未转染p73基因的细胞有显著性差异(P<0．05)。结论 高表达的p73基因能够降低肺腺癌细胞中VEGF、bFGF mRNA和蛋白表达水平，提示p73基因可能抑制人类肺腺癌的血管生成。     

非小细胞肺癌患者hOGG1基因启动子区域突变的研究

背景与目的 8-羟基鸟嘌呤DNA糖苷酶(8-hydroxygumine DNA glycosylase1,OGG1)是一种DNA修复酶,可以从DNA切除修复8-羟基鸟嘌呤(8-dihydro-8-oxoguanine,8-OH-G)。人类OGG1基因(hOGG1)的多态性可能会改变酶的活性而影响个体修复损伤DNA的能力,促进癌变。然而,hOGG1基因启动子区域的突变与非小细胞肺癌(non-small cell lung cancer,NSCLC)的关系尚不明晰。我们拟探讨hOGG1基因启动子区域的突变与NSCLC发生发展的潜在关系。方法选取苏州大学附属第一医院2003年1月-2005年12月新鲜手术切除的40例NSCLC组织标本,采用PCR-SSCP和直接测序的方法检测NSCLC及其对应的癌旁组织中hOGG1基因启动子区域的突变。结果在40例NSCLC患者中未发现hOGG1基因启动子区域的异常突变,但发现单核苷酸多态位点rs159153与TNM分期明显相关(P=0.008);同时发现吸烟者中淋巴结转移率明显较低(P=0.034)。结论单核苷酸多态位点rs159153和吸烟史可能对NSCLC的侵袭和转移潜在性提供预测。     

Fetal Adenocarcinoma of the Lung in a 25-Year-Old Woman

We report the case of a 25-year-old woman with a chance detection at x-ray of a well-defined mass in the right upper lobe during a medical examination. The patient suffered from a modest flu syndrome, with cough and fever. She was a current smoker. CT scan showed a homogeneous well-defined perihilar mass without calcifications, located in the right upper lobe and fully surrounded by aerated parenchyma. A right upper lobectomy with mediastinal lymph node sampling was performed. A pathologic diagnosis of well-differentiated fetal adenocarcinoma of the lung was made and staged as T2N0. Few cases of this type of malignancy have been reported in literature.     

DNA修复基因及其TP53共突变在肺腺癌免疫治疗疗效预测中的价值

目的 基于二代测序技术,探索DNA修复基因(DRGs)对肺腺癌免疫治疗疗效的预测价值.方法 选取癌症基因组图谱中肺腺癌两个独立数据集(分别为测试集和验证集).测试集中,依据肿瘤突变负荷评分15为阈值,分为低突变负荷组和高突变负荷组,分析不同肿瘤突变负荷与肺腺癌总生存的关系,并以KRAS/TP53共突变作为标准参照,分析...     

Analysis of EGFR Mutation Status in Algerian Patients with Non-Small Cell Lung Cancer

Background and objective: Epidermal growth factor receptor (EGFR) mutation status is used as a predictive biomarker for the tyrosine kinase inhibitors therapy in non-small cell lung cancer (NSCLC). The incidence of EGFR mutations appears to vary according to ethnic and geographical backgrounds. This retrospective study aimed to investigate the EGFR mutation status in Algerian NSCLC patients and its association with clinicopathological features. Methods: We examined the presence of EGFR mutations (Exons 19-21) in 58 unselected  NSCLC samples using PCR followed by direct sequencing. Results: The present study included 53 (91.4%) men and 5 (8.6%) women, with a median age of 59 (ranging from 44 to 94 years old). EGFR mutations were detected in 23 patients, with an overall rate of 39.6%. There were 21 (91.3%) cases with the exon-21 L585R single mutation and two (8.7%) with dual mutations of exon-19 deletions and L585R. EGFR mutations were more frequently found in patients with confirmed adenocarcinoma (14/27, 51.8%) than in non-adenomatous NCSCL subtypes (3/14, 21.4%; p=0.03). Furthermore, early stages of the disease were significantly associated with a higher rate of EGFR mutations (14/27, 51.8%) compared with those at  advanced stage (5/21, 23.8%; p=0.02). There were no significant differences in EGFR mutation frequency by age, gender, or smoking status. Conclusion: We found that Algerian NSCLC patients exhibited a high rate of EGFR mutations, which was quite similar to that in Asians population rather than Caucasian patients. Thus, TKI-based treatments may be more beneficial for Algerian patients with NSCLC. Further studies using a large number of patients are required to confirm our preliminary findings.     

nm23基因在肺癌中的表达

目的研究ｎｍ２３基因产物与肺癌临床病理间的关系。方法应用ＳＡＢＣ免疫组化法，检测６９例肺癌中ｎｍ２３基因产物二磷酸核苷激酶（ＮＤＰＫ）的表达情况。结果ｎｍ２３在肺癌中有较高表达，阳性率７９．７％（５５／６９），其中鳞癌１００％（３１／３１），腺癌７１．４％（２０／２８），小细胞癌４０％（４／１０），在鳞癌中的表达较腺癌及小细胞癌高（ｐ＜０．０５）。但ｎｍ２３的表达与肺鳞癌的分化程度无关（ｐ＞０．０５），与肺鳞癌、肺腺癌及其它肺癌有无肺门或纵隔淋巴结转移无关（ｐ＞０．０５）。结论提示肺癌的形成和转移与多基因、多步骤的遗传学改变有关，应将ｎｍ２３基因与其他因素进行同时研究，以准确反映肺癌恶性生物学行为的重要特点。     

Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis

IntroductionPathological examination of histopathological slides is a routine clinical procedure for lung cancer diagnosis and prognosis. Although the classification of lung cancer has been updated to become more specific, only a small subset of the total morphological features are taken into consideration. The vast majority of the detailed morphological features of tumor tissues, particularly tumor cells’ surrounding microenvironment, are not fully analyzed. The heterogeneity of tumor cells and close interactions between tumor cells and their microenvironments are closely related to tumor development and progression. The goal of this study is to develop morphological feature–based prediction models for the prognosis of patients with lung cancer.MethodWe developed objective and quantitative computational approaches to analyze the morphological features of pathological images for patients with NSCLC. Tissue pathological images were analyzed for 523 patients with adenocarcinoma (ADC) and 511 patients with squamous cell carcinoma (SCC) from The Cancer Genome Atlas lung cancer cohorts. The features extracted from the pathological images were used to develop statistical models that predict patients’ survival outcomes in ADC and SCC, respectively.ResultsWe extracted 943 morphological features from pathological images of hematoxylin and eosin–stained tissue and identified morphological features that are significantly associated with prognosis in ADC and SCC, respectively. Statistical models based on these extracted features stratified NSCLC patients into high-risk and low-risk groups. The models were developed from training sets and validated in independent testing sets: a predicted high-risk group versus a predicted low-risk group (for patients with ADC: hazard ratio = 2.34, 95% confidence interval: 1.12–4.91, p = 0.024; for patients with SCC: hazard ratio = 2.22, 95% confidence interval: 1.15–4.27, p = 0.017) after adjustment for age, sex, smoking status, and pathologic tumor stage.ConclusionsThe results suggest that the quantitative morphological features of tumor pathological images predict prognosis in patients with lung cancer.