肺腺癌中微乳头结构临床病理及预后意义的探讨

目的探讨肺腺癌中微乳头结构对肿瘤侵袭行为及其对预后的影响。方法选择具有完整临床病理及随访资料结果的肺腺癌91例,将病例分成微乳头结构阳性组（41例）和阴性组（50例）。阳性组按照该成分占肿瘤的多少又分成微乳头结构＋（占肿瘤的1％～10％）,＋＋（占肿瘤的11％～30％）,＋＋＋（超过肿瘤的30％）。结果总的5年生存率是64．8％。临床分期5年生存率分别为Ⅰ期88．9％、Ⅱ期46．2％、Ⅲ期23．8％。不同临床分期病例间的生存率差异有统计学意义（P=0．000）。微乳头结构含量多少与临床分期、肿瘤大小和5年生存率无关,P值分别是0．065、0．358、0．206。而微乳头结构阳性组和阴性组5年生存率分别是：41．5％和84．0％,P=0．000,且淋巴结转移率前者（65．9％）明显高于后者（20．0％）,P=0．000。有无微乳头结构与临床分期和肿瘤大小有关,P值均为0．000,即分期越晚,肿瘤越大,出现此结构的几率越高。而有无微乳头结构与性别、吸烟史无关。同一临床分期中阳性组与阴性组5年生存率分别是：Ⅰ期：78．6％、92．6％（P=0．1548）;Ⅱ期：30．0％,100％（P=0．0598）;Ⅲ期：17．7％,28．6％（P=0．4045）,但差异无统计学意义。结论肺腺癌中微乳头结构成分提示肿瘤高侵袭转移行为,是影响预后的重要因素,该病理形态的出现应提醒临床采取积极治疗措施并密切随访。     

人肺腺癌裸鼠皮下移植瘤淋巴转移模型的构建与筛选

目的构建人肺腺癌的裸鼠皮下移植瘤模型,探讨不同注射部位对肿瘤生长和淋巴转移的影响。方法 20只BALB/c裸鼠随机分为4组,每组5只。分别于左侧背部近腋窝、右侧背部近腋窝、左侧后肢和左后爪垫皮下注射A549细胞株,建立人肺腺癌移植瘤模型,考察各组裸鼠肿瘤生长和淋巴结转移情况。结果各组裸鼠成瘤明显,模型构建成功。背部近腋窝种植2组裸鼠肿瘤比后肢和爪垫种植的肿瘤出现时间早,生长速度快(P<0.05)。左侧背部近腋窝、右侧背部近腋窝、左侧后肢和左后爪垫皮下移植瘤的淋巴结转移率分别为41.7%、42.9%、23.1%和21.4%。其中左侧背部近腋窝注射最为方便。结论裸鼠左侧背部近腋窝皮下注射A549细胞操作方便,肿瘤易生长,淋巴转移率高,是构建人肺腺癌皮下移植瘤淋巴转移模型的优选方案。     

转移潜能不同的小鼠肺腺癌亚系的生物学性质的比较

本文利用来源于同一母系的具不同转移潜能的亚系LA1、LAD、LA5,比较研究了它们的细胞电泳速度、运动性及其与不同靶细胞或基质的粘附性。结果表明:三个亚系细胞的电泳速度、运动性与其转移潜能相一致,瘤细胞自身粘附性及其与成纤维细胞的粘附性与其转移潜能则相反。可见瘤细胞电泳速度的加快,运动能力的增强及自身粘附性的下降均有利于其侵袭和转移。     

肺腺癌预后代谢相关基因的生物信息学分析

目的 基于代谢基因的生物信息学构建肺腺癌预后模型及验证。方法 获取癌症基因组图谱(TCGA)数据库和基因表达数据集(GEO)肺腺癌相关数据,套索(LASSO)回归构建多基因预后模型并计算风险值(RS)。单因素、多因素Cox独立预后分析,通过受试者工作特征(ROC)曲线评价模型的ROC曲线下面积(AUC)并进行生存分析。构建列线图评价模型的可行性,通过基因集富集分析(GSEA)进行代谢基因功能富集分析。肿瘤免疫评估资源(TIMER)数据库分析患者RS与免疫细胞浸润以及与免疫检查点分子表达的相关性。结果 运用TCGA数据库基于18个代谢相关基因构建肺腺癌预后模型,RS可以作为独立的预后因子。ROC曲线下面积为0.713。生存分析显示,与高风险组相比,低风险组总体生存率更高,预后模型与免疫细胞的浸润以及与免疫检查点分子的表达有关。结论 代谢相关基因肺腺癌预后模型的RS是独立预后因子,模型具有较高的预后判断价值。     

肺腺癌罕见部位转移3例并文献复习

目的探讨3例罕见部位肺腺癌转移病例的临床病理学特征、诊断、鉴别诊断及预后。方法收集3例肺腺癌转移至卵巢、十二指肠、前列腺的临床资料,对其进行HE及免疫组化染色,并复习相关文献。结果例1女性,47岁,单侧附件囊实性占位,形态学有管囊状结构,首先考虑原发性肿瘤。免疫表型:Napsin A、TTF-1、CK7、CK(AE1/AE2)、ALK(D5F3)、CA125、Mucin-1、CEA阳性;例2女性,70岁,内镜提示十二指肠多发新生物,形态学示小肠黏膜间出现分化差的癌细胞。免疫表型:CK(AE1/AE2)、CK8/18、Napsin A、TTF-1阳性;例3男性,73岁,前列腺穿刺标本,形态学显示前列腺组织间可见分化差的癌伴坏死。免疫表型:CK(AE1/AE3)、CK8/18、TTF-1阳性,Ki-67增殖指数较低,结合肺部占位,可考虑肺腺癌转移。结论 3例患者均以转移灶就诊,为肺腺癌罕见转移部位,尤其例1以单侧附件单囊性附壁结节形式出现的转移癌极其罕见,ALK基因为融合型,值得关注;肺腺癌转移至小肠及前列腺可能提示患者预后较差。     

高表达SKA3预示肺腺癌患者预后不良

目的:旨在揭示纺锤体与动粒相关蛋白3(SKA3)在肺腺癌中的表达、潜在的临床价值及其可能的调节机制.方法:利用癌症基因组图谱(TCGA)数据库RNA表达数据分析SKA3在肺腺癌中的表达,Wilcoxon秩和检验和逻辑回归分析肺腺癌患者的临床病理学特征与SKA3之间的相关性.Cox回归和Kaplan-Meier生存分析与...     

肺腺癌眼球转移1例并文献复习

目的通过分析1例肺腺癌眼部转移病例,探讨肺腺癌眼球转移的临床和病理特征。方法回顾性分析1例肺腺癌眼球转移病例的临床表现、病理特征及免疫组化表型,并进行文献复习。结果患者男性,51岁,以右眼渐进性视力下降6月为主诉入院。镜下可见(眼球)视神经盘处中度异型腺体呈浸润性生长,并产黏液伴坏死形成,累及视网膜、脉络膜及巩膜,未侵透巩膜,压迫视神经,但未见明确侵犯;视神经断端及周围软组织未见癌浸润。免疫组化染色结果:AE1/AE3(+)、CK7(+)、TTF-1(+)、Napsin A(+)、CDX-2(-)、HMB45(-)、CK20(-)、Vimentin(-)、Ki67(80%+)。综上:腺癌,中分化,结合临床考虑肺脏来源。结论对于以眼部症状首发,有肺癌家族史和胸片提示肺部结节的患者,还应进一步完善相关检查,以缩短疾病的诊断周期,及早进行对症治疗。     

高转移肺腺癌细胞系Anip973中存在3p24的断裂重排

目的 确认一对细胞来源相同、转移能力不同的人肺腺癌细胞系AGZY83－a和Anip-973中3号染色体短臂的分子细胞遗传学差异。方法 采用3p涂染探针对两细胞系进行G显带后荧光原位杂交。结果 两细胞系共同存在标记染色体der(3;5)(3pter→3p10∷5q10→5qter)和der(1)t(1;12;3)(3pter→3q12∷12q24→12q15∷1p22→lqter)。不同的是，低转移细胞系AGZY83－a中存在1条正常的3号染色体；而在高转移细胞系Anip973中，存在1条涉及3号染色体断裂重排的标记染色体＋（？∷3p24→3qter)，断裂点发生于转移相关基因RAB5A的染色体区域。结论 高转移肺腺癌细胞系Anip973中3号染色体上RAB5A基因区3p24的断裂重排与该基因的高表达一致。     

C-erbB2过度表达对肺腺癌预后的临床观察

目的：前瞻性探讨C-erbB2表达等指标对肺腺癌的复发及生存期的影响。方法：采用免疫组化等方法检测70例肺腺癌的病理标本C-erbB2表达等，并长期随访患者。结果：患者的KPS评分、肿块大小、有无远处转移、TNM分期以及C-erbB2表达等与肺腺癌复发及生存期有关（P〈0．05）。结论：患者的KPS评分、肿块大小、有无淋巴结转移、TNM分期以及C-erbB2表达等指标可以预测肺腺癌的预后。     

rhPRL对骨髓移植小鼠结肠腺癌肺转移的实验性治疗及免疫机？…

通过体内实验进一步观察荷瘤小鼠放疗加骨髓移植后并用ｒｈＰＲＬ的治疗效果。选用Ｃ５７ＢＬ／６纯系小鼠，静脉注入同基因结肠腺癌细胞（ＭＣＡ－３８），待定向形成大量肺转移结节（１０ｄ）时进行全身致死放疗并进行ＳＢＭＴ，同时进行ｒｈＰＲＬ治疗。在治疗开始的１０ｄ和２０ｄ分别处死部分动物观察肺癌结节、骨髓ＣＦＵ－Ｃ、脾脏Ｔ细胞丝裂原反应与ＮＫ活性，最终计算生存期。结果表明ｒｈＰＲＬ对荷瘤小鼠具明显的治疗效果     

Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and prognosis of lung adenocarcinoma

Metastasis is a major cause of cancer recurrence or death. This study attempted to quantitatively identify different proteins in metastatic lung adenocarcinoma. The N/T quotient [number of metastatic lymph nodes (n)/tumor diameter (cm)] was used to select samples with an extreme metastatic phenotype. Among the six fresh frozen lung adenocarcinoma specimens, the three showing the highest N/T quotient represented the metastatic group, and others with the greatest tumor diameters without metastasis represented the non-metastatic group. After 2-dimensional electrophoresis, the significantly different protein spots were selected by image analysis and analyzed with MALDI-TOF mass spectrometry. Acyl-CoA thioesterase 8 isoform c (ACOT8) was one of most overexpressed proteins in the metastatic group, and it was validated by Western blot and immunohistochemical staining on 108 paraffin-embedded tumor samples. High ACOT8 expression was correlated with lymph node metastasis (p = 0.002), recurrence (p = 0.034), predominant histologic subtypes (p = 0.007), and higher stage (p = 0.005). In multivariate analysis, high ACOT8 expression was significantly associated with increased risks of lymph node metastasis (p = 0.009) and cancer-related death (p = 0.030), independent of clinical factors. ACOT8 may be a candidate prognostic biomarker and therapeutic target of lung adenocarcinoma.     

Surgical treatment of non-small cell lung cancer with isolated synchronous brain metastases

This study is a retrospective examination of our experiences with patients who underwent treatment of isolated synchronous brain metastases coupled with primary non-small cell lung cancer. From January 1995 to June 2004, 12 patients presented with isolated synchronous brain metastases coupled with primary non-small cell lung cancer. The patient was comprised of 8 men and 4 women. The median age was 52 yr, in a range of 32 to 75 yr. Median follow-up duration was 10.6 months, in a range of 2 to 55.8 months. Recurrence developed in 7 patients, and the median interval from 1st treatment to recurrence was 4.5 months (2.8-6.5 months). The overall 1-yr survival rate was 61.7%. The 1-yr survival rates for pathologic N0 and N1 cases were 75% and 66.7%, respectively. The median survival duration for pathologic N2 was 6.2 months (95% CI, 4.8-7.5 months). The 1-yr survival rate for cases of single brain metastasis was 75%. Based on our current observations, we could speculate that aggressive management of primary non-small cell lung cancer and isolated synchronous brain metastases was beneficial in a selected group of patients, as long as the brain lesions and pulmonary lesions were limited or resectable.     

Immunolocalization of glycodelin in human adenocarcinoma of the lung, squamous cell carcinoma of the lung and lung metastases of colonic adenocarcinoma

Glycodelin (Gd), which is localized in cells of bronchial epithelium, type II pneumocytes and alveolar macrophages in rats and humans, plays an important role in the pulmonary immune response in asthmatic inflammation. In this study, sections of paraffin-embedded tumor adjacent lung tissue and sections of adenocarcinoma of the lung, squamous cell carcinoma of the lung and metastases of colonic adenocarcinoma were investigated for the distribution and expression of Gd using a polyclonal anti-Gd antibody. Glycodelin protein is located in the cytoplasm of bronchial epithelial cells, pneumocytes and alveolar macrophages. Furthermore, Gd is expressed in adenocarcinoma and squamous cell carcinoma of the lung as well as in lung metastases of colonic adenocarcinoma. Densitometric analyses showed a significantly increased expression of glycodelin protein in cancer tissue compared to tumor adjacent lung tissue. The Gd protein level was 1.7–2.6-fold increased in lung carcinoma compared to tumor adjacent lung tissue. The Gd protein level did not differ from each other between the investigated types of cancer tissue. Because these data validate the recent findings of Gd mRNA expression, it may be concluded that glycodelin plays an important role in the pathogenesis of lung cancer and lung metastases.     

Cribriform pattern in lung invasive adenocarcinoma correlates with poor prognosis in a Chinese cohort

The 2011 International　Association　for　the　Study　of　Lung　Cancer/American　Thoracic　Society/European　Respiratory　Society (IASLC/ATS/ERS) lung adenocarcinoma classification and the following 2015 WHO classification have both been validated for their predictive values of histologic subtypes for prognosis. We sought to investigate the clinicopathological and prognostic significance of the cribriform pattern in lung adenocarcinomas. Histologic subtypes were evaluated in 395 patients who underwent complete resection for invasive lung adenocarcinomas between 2011 and 2013. Cribriform pattern was correlated with clinicopathological factors as well as molecular and survival data. One hundred and thirty cases (33%) were present with cribriform pattern (5–100%; mean?±?SD, 24% ± 22%). Thirty two (8%) of those were reclassified into cribriform predominant tumors. Presence of cribriform pattern (≥5%) was significantly associated with lymph/vascular invasion (P＜0.001), nodal positivity (P = 0.003), higher T stage(P = 0.005) and higher TNM stage (P = 0.001). Cribriform pattern (≥10%) was highly associated with worse disease-free survival (DFS) and overall survival (OS) (mean DFS: 42.6 months, P?<?0.001; mean OS: 64.1 months, P = 0.012). The DFS or OS for cribriform predominant tumors was similar to that for solid or micropapillary tumors. In multivariate analysis, cribriform pattern (≥10%) or cribriform predominant subtype was an independent predictor for DFS. Cribriform pattern was a specific pattern compared to other acinar patterns, presenting with more aggressive behavior. Moreover, presence of cribriform pattern was a strong predictor for worse prognosis and should be considered a high grade pattern. Our study provides further evidence for cribriform pattern to be acknowledged as an independent subtype in the future classification.     

Prognosis of non-small cell lung cancer with synchronous brain metastases treated with gamma knife radiosurgery

The clinical outcome and prognostic factors of patients with synchronous brain metastases from non-small cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKS) were analyzed. A total of 35 patients with NSCLC underwent GKS as an initial treatment for metastatic brain lesions of synchronous onset. The period of survival and various prognostic factors such as age, gender, performance status, multiplicity of the brain lesions, intracranial tumor volume, and extent of the primary tumor were analyzed. The overall median survival time for this series was 12 months (range 0.75 to 43 months) from the diagnosis. Of the 21 patients who were no longer alive at the conclusion of this study, only 7 (33.3%) died of neurological causes. Multivariate analysis of these data revealed that N stage, whole-brain radiotherapy (WBRT), and chemotherapy were significant predictors for survival (p<0.05). Survival of patients with NSCLC and synchronous brain metastases is mainly dependent upon the progression of the systemic disease, provided that the cerebral lesions are treated adequately with local treatment modalities including radiosurgery. Application of radiosurgery as an initial treatment option and aggressive local and systemic modalities to control extracranial disease may improve survival.     

CA724 is a novel factor for predicting the unresectability in pancreatic adenocarcinoma

This study aimed to assess the relationship between serum CA724 levels and the unresectability of pancreatic adenocarcinoma. A total of 302 patients with pancreatic adenocarcinoma were analyzed for the potential association between serum CA724 levels and the unresectability of pancreatic adenocarcinoma. Serum CA724 levels in patients with unresectable pancreatic adenocarcinoma were remarkably higher than those with resectable pancreatic adenocarcinoma (P < 0.001). Patients with elevated serum CA724 levels exhibited a 12.27-fold higher risk of unresectability than those with normal serum CA724 levels after adjusting for age, sex, and tumor location (95% CI = 5.28-28.51, P < 0.001). The analysis of receiver operating characteristics demonstrated that CA724 had superior predictive value to other tumor markers (AUC was 0.77 ± 0.03, 0.65 ± 0.04, and 0.62 ± 0.04 for CA724, CA125, and CA199, respectively). CA724 appeared to be a better predictor of unresectability than CA199 and CA125.     

Correlated low IGF2BP1 and FOXM1 expression predicts a good prognosis in lung adenocarcinoma

IGF2BP1 and FOXM1 are shown to be critical in the regulation of caner progression. However, the prognostic value of IGF2BP1 in lung adenocarcinoma and its relationship with FOXM1 still remains unclear. In this study, the expression and biological significance of both IGF2BP1 and FOXM1 were evaluated in 188 lung adenocarcinoma, at mRNA and protein levels. We showed that mRNA and protein levels of IGF2BP1 and FOXM1 were upregulated in lung adenocarcinoma compared to adjacent non-cancerous tissues. High IGF2BP1 expression was correlated with a poor prognosis for lung adenocarcinoma patients. Moreover, IGF2BP1 expression was positively associated with FOXM1 expression. Meanwhile, the findings indicated that low IGF2BP1 combined with low FOXM1 expression, was negatively correlated with pathological stage and lymph node metastasis, predicted good outcomes for lung adenocarcinoma patients. Additionally, low IGF2BP1 and FOXM1 expression status, is an independent prognostic factor for lung adenocarcinoma after surgical resection. We demonstrate that low IGF2BP1 and FOXM1 expression can serve as a potential factor for the clinical diagnosis and prognosis of lung adenocarcinoma, and targeted inhibition of IGF2BP1 and FOXM1 might be an alternative strategy for the management of lung adenocarcinoma.     

Clonal selection of adenocarcinoma of the lung as determined by loss of heterozygosity

Although the most frequently altered oncogenes and tumor suppressor genes in non-small cell lung carcinoma (NSCLC) have been recognized, the exact mechanisms responsible for the progression and phenotypic expression of carcinoma, particularly adenocarcinoma of the lung are uncertain. Fifty-six cases of adenocarcinoma of the lung (11 bronchioloalveolar carcinoma [BAC], 25 stage 1, 20 stage 2) and paired 19 lymph node metastases (LNM) of stage 2 adenocarcinomas were analyzed for loss of heterozygosity (LOH). Analysis included a panel of 14 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 10q, and 17p. LOH on chromosomes 1p (P = 0.0209) and 17p (P = 0.0274) was more frequently present in stage 1 adenocarcinomas than in BAC. There was no significant difference between BAC, stage 1 and stage 2 adenocarcinoma in the frequency of LOH at individual chromosomal arms. The pattern of LOH in LNM of stage 2 adenocarcinoma was similar to the primary tumor. Overall fractional allelic loss (FAL) was significantly different between BAC and stage 1 invasive adenocarcinoma (P = 0.0013), and it was significantly higher in stage 1 adenocarcinoma than in stage 2 adenocarcinoma (P = 0.0062) and their LNM (P = 0.0001). Stage 2 adenocarcinomas showed significantly higher overall FAL than their LNM (P = 0.022). Our study failed to identify a single target gene responsible for progression of lung adenocarcinoma. A trend towards lower overall FAL in advanced stage tumors and in their metastases suggests that clonal selection may play a role in lung adenocarcinoma progression.     

岩藻糖在肺癌及其脑转移癌组织中的表达和意义

目的 观察岩藻糖在肺癌及其脑转移癌组织中的表达,探讨岩藻糖与肺癌脑转移及预后的关系。方法 应用亲合组织化学染色法观察岩藻糖在３９例脑转移癌及其原发癌中的表达。结果 原发癌和转移癌均表达岩藻糖者２１例,均不表达者１２例,仅原发癌表达者２例,仅转移癌表达者４例;转移癌岩藻糖阳性强度强于原发癌,差异有显著性意义（Ｐ＝０．００１５）转移癌岩藻糖阳性面积百分比大于原发癌,差异有非常显著性意义（Ｐ＝０．００１     

肺腺癌巨噬细胞M2表型边缘极化效应观察及预后分析

目的:探讨肺腺癌边缘区巨噬细胞M2表型的极化效应、边缘/中心比值及对预后的影响。方法:采用双重免疫组化技术,观察巨噬细胞CD163+/CD68+表型(M2表型)在49例原位肺腺癌(AIS)、11例微小浸润性腺癌(MIA)、57例浸润性腺癌(IA)边缘区及中心区的分布规律和差异,探讨巨噬细胞边缘极化效应及边缘/中心比值在肺腺癌进程中的作用及机制。采用单因素Kaplan-Meier生存曲线分析及多变量Cox生存分析探讨M2表型边缘极化状态与预后的关系。结果:肺腺癌边缘区M2型巨噬细胞较中心区域呈现极性聚集,具有显著差异(P0.01)。根据中位数分高、低极化组,低极化组AIS中M2型巨噬细胞计数值与MIA及IA比较未见明显差别,但其在高、极化组AIS中的计数值依次低于MIA和IA,差异有统计学意义(均P0.01)。单因素Kaplan-Meier生存曲线分析及log-rank检验结果显示边缘区巨噬细胞M2表型数量及边缘/中心比值与生存时间呈负相关(2=44.71,P0.01;2=21.75,P0.01)。多变量Cox生存分析表明M2表型边缘高极化状态和边缘/中心比值是独立的预后危险因素(P0.01)。结论:巨噬细胞M2表型在肺腺癌边缘区存在边缘极化效应,其边缘极化状态和边缘/中心比值是独立的预后危险因素,因此术前穿刺判断边缘极化状态或术后活检检测M2型巨噬细胞型边缘/中心比值可能是评估预后的一种有效方法。