伴微乳头结构肺腺癌的病理和临床特征研究进展

2011年,国际肺癌研究协会（InternationalAssociationfortheStudyof LungCancer,IASLC）、美国胸科学会（Americanthoracicsociety,ATS）和欧洲呼吸学会（European Respiratory Society,ERS）同时将微乳头结构（micropapillary pattern,MPP）为主型肺腺癌划分为一种独立的病理类型,并将其定义为微乳头型肺腺癌（micropapillary-predominant adenocarcinoma,MPA）,其组织学特异性和临床特殊性受到了学者的广泛关注。伴微乳头结构肺腺癌（lung adenocarcinoma with a micropapillary pattern,MPPAC）常具有侵袭性强、转移率高、术后易复发等预后不良的生物学行为。目前,MPPAC的临床诊断有赖于术后病理组织学检查,但针对其病理学异质性、分子生物学特点、临床特征和预后等方面的系统性研究较少。本文对MPPAC的病理和临床特征相关研究进展作一综述。     

伴微乳头结构的肺腺癌恶性潜能机制研究

  目的  探讨伴微乳头成分的肺腺癌(pulmonary adenocarcinoma with a micropapillary pattern, MPPAC)上皮间质转化和增殖调亡特征, 为临床评价其恶性潜能提供理论依据。  方法  根据2011年发表的肺腺癌新分类诊断标准, 以是否伴有微小乳头状结构(micropapillary pattern, MPP)将120例肺腺癌病例分为64例MPP阳性组, 56例MPP阴性组。免疫组织化学法检测Vimentin、E-cadherin、Capase-3、pEGFR的表达。  结果  120例肺腺癌病例中pECFR在女性(P=0.035)、非吸烟(P=0.017)患者中高表达。Vimentin在MPP阳性组的表达(28.1%)高于MPP阴性组(16.1%)并且其多表达于微乳头结构腔内散落的细胞; Caspase-3在MPP阳性组高表达(P=0.001)。  结论  微乳头结构的腔内散落细胞表现间质表型有利于癌细胞浸润转移, 伴乳头结构的肺腺癌有其独特的分子生物学特征。      

伴微乳头成分的肺腺癌EGFR KRAS基因突变和临床病理学特征相关研究

  目的   探讨伴微乳头成分的肺腺癌(pulmonary adenocarcinoma with a micropapillary pattern, MPPAC) EGFR、KRAS基因突变情况及其临床病理学特征。   方法   根据2011年的肺腺癌新分类诊断标准, 以是否伴有微小乳头状结构(micropapillary pat tern, MPP), 将144例肺腺癌病例分为MPP阳性组77例和MPP阴性组77例。MPP阳性组中又按MPP所占比例分为(+、++、+++) 三亚组。RT-PCR法检测两组EGFR、KRAS基因突变情况。   结果   在144例肺腺癌病例中EGFR突变62例(43.1%), KRAS突变9例(6.25%), EGFR突变与性别(P=0.018) 和肿瘤体积(P=0.016) 有关。MPP阳性组EGFR突变率高于MPP阴性组(P < 0.001);KRAS突变率低于MPP阴性组(P=0.016)。EGFR基因突变频率在MPP三亚组中无明显不同(P=0.932)。   结论   伴微乳头结构的肺腺癌EGFR突变频率高于肺腺癌其它亚型, KRAS突变频率低于肺腺癌其它亚型, 说明其有独特的分子生物学特点。      

肺微乳头型腺癌诊疗及预后的研究进展

肺微乳头型腺癌发病率低, 术后易复发和转移, 患者预后差。文章总结了肺微乳头型腺癌的影像学与组织病理学特征, 并讨论了外科术式、化疗及靶向药物治疗方案对患者预后的影响, 旨在加深对肺微乳头型腺癌的认识。     

CT值鉴别纯磨玻璃密度的肺原位腺癌与微浸润腺癌的价值

摘 要：［目的］ 探讨平扫CT值对表现为纯磨玻璃密度的肺原位腺癌（AIS）和微浸润腺癌（MIA）的鉴别诊断价值。［方法］ 回顾性分析表现为纯磨玻璃密度的肺原位腺癌32例、微浸润腺癌45例的术前资料,比较两组病例平扫CT值,并通过ROC曲线确定两组病例CT值的最佳截断点。［结果］ 原位腺癌与微浸润腺癌的CT值不同（-595.37±79.49Hu vs -497.62±121.08Hu;Z=-3.406,P<0.05）,CT值对于原位腺癌与微浸润腺癌的诊断价值较好（曲线下面积0.729,95%CI：0.618~0.839,P<0.05）,-491.55Hu为AIS与MIA的最佳CT值截断点（灵敏度为48.9%,特异性为93.7%）。［结论］ 平扫CT值对于肺原位腺癌和微浸润腺癌的诊断有一定指导意义,当CT值＞-491.55Hu时,病灶为MIA可能性大;当CT值＜-491.55Hu时,病灶为AIS可能性大。     

肺腺癌癌胚抗原计量学的研究

本文对术后随访已逾5年的51例肺腺癌进行癌胚抗原(CEA)的标记研究,对其中36例进行计量学研究,结果阳性率为80％,最高值为220.0125,最低值为0。在29例管状腺癌中,以中等度分化者平均值最高(105.0725)。CEA计量与肺门淋巴结转移与否及肿瘤大小之间无萌显关系(P>0.05),计量值在11～100之间者预后好(P<0.05)。     

The Value of Multislice Spiral Computed Tomography in Demonstrating the Relationship between Bronchial and Peripheral Lung Cancer

OBJECITVE To investigate the value of multislice spiral computed tomography (MSCT) in demonstrating the relationship between bronchial and peripheral lung cancer.METHODS MSCT was used to conduct volumetric targeted scans of 0.5 mm collimation for 53 cases of peripheral lung cancer and to demonstrate the relationship between bronchial and peripheral lung cancer by multiplanar reconstrUctions(MPR) images, curved multiplanar reformations(CMPR) and surface shaded display(SSD). The results were compared with macroscopic and microscopic specimens.RESULTS 1) All the bronchi at the 3rd to 7th order were displayed clearly and completely with this CT protocol. The tumors that were related to the bronchus included 29 (96.7%) adenocarcinomas and 13 (76.5%) squamous-cell carcinomas. Statistical analysis showed that there was no significant difference between the two groups (x2 =2.8, P ＞0.05). 2) The tumorbronchus relationship was divided into four subtypes, i.e. type Ⅰ: the bronchus was obstructed by a tumor, type Ⅱ: the bronchus was obstructed when penetrated by a tumor with tapered narrowing; type Ⅲ: the bronchial lumen shown within the tumor was unobstructed and intact, type Ⅳ: the bronchus ran at the periphery of a tumor, with an intact or narrowed lumen.3) Type Ⅰ occurred in 58.5% (31 cases), in which squamous-cell carcinoma was slightly more common than adenocarcinoma. Both type Ⅱ and type Ⅲ were seen in 15.1%(eight cases of each), of which all were adenocarcinomas. The incidence rate of type Ⅳ was 28.3% (15 cases), of which adenocarcinoma was slightly more frequent than squamous-cell carcinoma. 4)Squamous-cell carcinoma was more common than adenocarcinoma in the tumors in the fourth-order bronchus, whereas adenocarcinoma was more common than squamous-cell carcinoma in tumors with a relationship to the sixth-order bronchus.CONCLUSION MSCT with volumetric targeted scans of ultra-thin sections were conducted followed by MPR,CMPR and SSD reconstruction. This procedure can accurately demonstrate the relationship between the nature of tumors and bronchus and thereby to some extent reflect pathological changes.     

Characteristics of advantages of positron emission tomography over computed tomography for N-staging in lung cancer patients

OBJECTIVE: We analyzed the characteristics of advantages of positron emission tomography (PET) over computed tomography (CT) for N-staging in lung cancer patients. METHODS: Preoperative PET and CT scans were performed for 2057 lymph node stations in 205 patients with peripheral-type lung cancer. The advantages of PET over CT for N-staging were analyzed among lymph node locations and histological subtypes. RESULTS: The pathological N-stages were N0 in 143 patients, N1 in 31, N2 in 24 and N3 in 7. PET was able to diagnose N0, N2 and N3 diseases more accurately than CT (P=0.03, 0.01 and 0.02, respectively), but there was no significant difference between the two modalities for N1 disease. In the upper mediastinal lymph node stations, both false-negative and false-positive were significantly less frequent with PET than with CT (P=0.001). In the lower mediastinal and supra clavicle lymph nodes, PET showed a lower frequency of false-negative than CT (P=0.04 and 0.003, respectively), but there was no significant difference in the frequency of false-positive between the two modalities. Among histological types, PET could stage adenocarcinoma with less frequent false-negative and squamous cell carcinoma with less frequent false-positive than CT (P=0.02 and 0.005, respectively). CONCLUSION: For N-staging, PET was superior to CT for the following: (1) more accurate for N0, N2 and N3 diseases but not for N1; (2) lower frequency of false-positive in the upper mediastinal nodes; and (3) lower frequencies of false-negative in adenocarcinoma and false-positive in squamous cell carcinoma. Recognizing these advantages of PET could make the N-staging of lung cancer more accurate.     

Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner

The aim of this study was to evaluate the usefulness of annual screening for lung cancer by low-dose computed tomography (CT) and the characteristics of identified lung cancers. Subjects consisted of 5483 general population aged 40-74 years, who received initial CT scans in 1996, followed by repeat annual scans for most subjects in 1997 and 1998, with a total of 13 786 scans taken during 1996-1998. Work-up examinations for patients with suspicious lesions were conducted using diagnostic CTs. The initial screening in 1996 detected suspicious nodules in 279 (5.1%) of 5483 subjects, and 22 (8%) were confirmed surgically to have lung cancer. Corresponding figures in 1997 and 1998 screening studies were 173 (3.9%) of 4425 and 25 (14%) of 173, and 136 (3.5%) of 3878 and 9 (7%) of 136, respectively. The sensitivity and specificity of detecting surgically confirmed lung cancer were 55% (22/40) and 95% (4960/5199) in 1996 and 83% (25/30) and 97% (4113/4252) in 1997 screening, respectively. 88% (55/60) of lung cancers identified on screening and surgically confirmed were AJCC stage IA. Our trial allowed detection of nearly 11 times the expected annual number of early lung cancers. Repeat CT allowed the detection of more aggressive, rapidly growing lung cancers, compared to those in the initial screening.     

多层螺旋CT灌注成像在胸部肿瘤诊断和治疗中的应用

目的：探讨多层螺旋CT（MSCT）胸部肿瘤灌注成像方法及临床应用价值。方法：对11例胸部肿瘤患者进行MSCT灌注成像,先用常规CT平扫确定肿瘤中心部位,然后进行肿瘤灌注扫描,扫描部位以肿瘤中心为主,采用电影扫描技术（1r/0.75s）层厚0.6mm流速5ml/s剂量50ml,注射造影剂同时进行CT扫描,扫描总时间40s。扫描图象经工作站处理,计算并分析图象和灌注参数,包括：动脉灌注量AP（ArtPerf）,静脉灌注量PP（PortPerf）,总灌注量TP（TotalPerf）和灌注指数PI。结果：所有肿瘤的灌注图象均可以清晰直观的显示肿瘤大小和轮廓。所有肿瘤灌注参数均明显增高。可定量检测肿瘤内部组织灌注状态。图象清晰,分辨率高。结论：SSMSCT灌注成像检查是一种准确且简捷的定量评估肿瘤血流灌注状态的检查方法。     

Three-year findings of an early lung cancer detection feasibility study with low-dose spiral computed tomography in heavy smokers.

BACKGROUND: Low-dose spiral computed tomography (sCT) showed a four-fold increase in the detection rate in high-risk subjects and a higher percentage of stage I lung cancer in comparison with chest X-ray. However, there is a considerable discrepancy among studies in the percentage of lung nodules, overall lung cancer and stage I detection rate. Subjects and methods: From April to December 2001, 520 asymptomatic volunteers aged >or=55 years with a history of cigarette smoking >or=20 pack-years and no previous cancer were enrolled to receive an annual sCT of the chest for five consecutive years. RESULTS: Seventy three per cent were male, median age was 59 years and 91% were current smokers. At baseline, nodules >or=5 mm were detected in 114 (22%) undergoing sCT; the size of lung nodules ranged from 5 to 9.9 mm in 81.5% of the cases. Five (1%) cases of lung cancer were detected. In two additional cases a pathological diagnosis of atypical adenomatous hyperplasia was made. Three new cases of lung cancer were detected in the second and third year of the study. One interval case was detected during the third year. CONCLUSIONS: Despite some promising data, convincing evidence from ongoing randomized trials is needed to support the routine use of sCT as a recommended tool for screening of lung cancer.     

双源计算机断层扫描在肺癌病理类型及临床分期中的应用价值

目的双源CT在肺癌病理类型及临床分期中的应用价值。方法对86例肺癌患者行双源CT检查,依据病理类型分为腺癌组和鳞状细胞癌组,比较两组患者主动脉达峰时及达峰后第40、60、100秒的净增CT值;依据第8版国际肺癌TNM分期标准,比较不同TNM分期(Ⅰ期13例,Ⅱ期26例,Ⅲ期34例,Ⅳ期13例)患者的标准化碘浓度(NIC)。以受试者工作特征(ROC)曲线及曲线下面积(AUC)分析NIC对肺癌TNM分期的诊断效能。结果腺癌组患者在主动脉达峰时及达峰后第100秒的净增CT值均高于鳞状细胞癌患者,差异均有统计学意义(P﹤0.05);达峰后第40、60秒,两组患者净增CT值比较,差异均无统计学意义(P﹥0.05)。随TNM分期的增加,肺癌患者的NIC值随之增加,差异有统计学意义(P﹤0.05),其中Ⅲ、Ⅳ期肺癌患者的NIC值均高于Ⅰ、Ⅱ期患者,差异均有统计学意义(P﹤0.05)。NIC诊断肺癌TNM分期的AUC为0.925(95%CI:0.855~0.995),灵敏度为86.1%,特异度为88.6%,最佳截断值为0.425。结论双源CT定量参数能间接反映肿瘤的病理类型,在肺腺癌和鳞状细胞癌及临床分期的诊断中发挥重要作用。     

Advances and perspectives in lung cancer imaging using multidetector row computed tomography

The introduction of multidetector row computed tomography (CT) into clinical practice has revolutionized many aspects of the clinical work-up. Lung cancer imaging has benefited from various breakthroughs in computing technology, with advances in the field of lung cancer detection, tissue characterization, lung cancer staging and response to therapy. Our paper discusses the problems of radiation, image visualization and CT examination comparison. It also reviews the most significant advances in lung cancer imaging and highlights the emerging clinical applications that use state of the art CT technology in the field of lung cancer diagnosis and follow-up.     

Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: a nested case-control study

We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RARbeta2, p16(INK4A) and RASSF1A genes was evaluated by methylation-specific PCR in tumor samples of 29 CT-detected lung cancer patients, of which 18 had tumor-sputum pairs available for the analysis, and in the sputum samples from 112 cancer-free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT-detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RARbeta2, 12/29 (41.4%) for p16(INK4A) and 15/29 (51.7%) for RASSF1A. Twenty-three of twenty-nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RARbeta2 and 1/18 (5%) for both RASSF1A and p16(INK4A). At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer-free smokers was observed in 58/112 (51.7%) for RARbeta2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RARbeta2, p16(INK4A) and RASSF1A promoters is present in spiral CT-detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection.     

多排螺旋CT显示支气管与外周肺癌关系的价值

目的 研究多排螺旋CT(MSCT)显示支气管与外周肺癌关系中的价值。方法 采用MSCT对53例外周肺癌行层厚为0．5mm的容积靶扫描,通过多层面或曲面重建(MPR or CMPR)以及表面遮盖显示(SSD)的方法,显示支气管与外周肺癌的关系。将结果与手术标本、病理切片对照。结果 (1)全部第3—7级支气管均全程清晰、完整的显示,肿瘤与支气管有关系者：30例腺癌中29例(96．7％),17例鳞癌中13例(76．5％)。(2)肿瘤-支气管关系分为4型：Ⅰ型：支气管被肿瘤截断;Ⅱ型：支气管进入肿瘤锥状中断;Ⅲ型：支气管在肿瘤内保持通畅;VI型：支气管紧贴肿瘤边缘走行,形态正常或受压移位。(3)Ⅰ型发生率为58．5％(31／53),其中鳞癌略多于腺癌;Ⅱ型和Ⅲ型均为15．1％(8／53),仅见于腺癌;Ⅳ型为28．3％(15／53),腺癌略多于鳞癌。(4)与第4级支气管相关的肿瘤,鳞癌多于腺癌;与第6级支气管相关的肿瘤,腺癌多于鳞癌。结论 采用MSCT,超薄层靶扫描后行MPR、CMPR和SSD重建能准确地显示肿瘤-支气管关系,反映一定的病理改变。     

tRNA-based prognostic score in predicting survival outcomes of lung adenocarcinomas

As the most abundant noncoding RNA in cells, tRNA plays an important role in tumorigenesis and development. The report of tRNA on the pathogenesis of lung adenocarcinoma is rare. It is of great clinical significance to explore the relationship between tRNA expression and prognosis of lung adenocarcinoma. The expression level of tRNAs in lung adenocarcinoma tissues and paracarcinoma tissues was detected using a tRNA RT-qPCR array. A total of 104 lung adenocarcinomas were included in the analysis of the correlation between candidate tRNAs expression and prognosis. A tRNA-based prognostic model was constructed and validated using Cox proportional hazards regression. A nomogram was built to help clinicians develop treatment strategies. We screened a series of differentially expressed tRNAs between lung adenocarcinoma tissues and paracarcinoma tissues. Among these tRNAs, tRNA^Asn_ATT, tRNA^Ile_AAT, tRNA^Leu_TAA, mt-tRNA^Trp_TCA, mt-tRNA^Leu_TAA, tRNA^Pro_AGG, tRNA^Lys_CTT^-1 and tRNA^Leu_AAG were associated with the clinicopathological characteristics of lung adenocarcinoma. tRNA^Lys_CTT^-1, mt-tRNA^Ser_GCT and tRNA^Tyr_ATA were associated with cancer-specific survival. We constructed a prognostic model for lung adenocarcinoma using specific tRNA expression levels as reference factors. Multivariate analyses showed that tRNA-based prognostic score was a significant and important prognostic factor. The prognostic model based on the tRNAs expression signatures can help predict the prognosis of patients with lung adenocarcinoma.