胸水中肺腺癌细胞与血清中PTN多效蛋白分子生物学的研究

通过检测PTN蛋白在肺腺癌患者术前血清标本及相对应的恶性胸水肺腺癌细胞2种不同标本中的表达及对比其表达的差异,探讨其诊断意义.利用Western-blot免疫印迹方法检测50例恶性胸水及相对应的术前血清,并对肺腺癌细胞进行石蜡包埋、免疫细胞化学检查.同时分别以10例正常献血者血清、20例胸水良性增生细胞作为对照.肺腺癌患者血清和恶性胸水细胞中PTN蛋白的表达分别高于对照组PTN蛋白的表达,恶性胸水中PTN蛋白的表达59.0％ (49/83)高于肺腺癌患者血清中PTN蛋白的表达32.5％ (27/83).差异均具有统计学意义(P＜0.05),恶性胸水肺腺癌细胞中的PTN蛋白表达和波形蛋白Vimentin呈正相关关系(P ＜0.01,r =0.728),而与钙粘连蛋白E-ca呈负相关.PTN蛋白在肺腺癌患者血清和恶性胸水细胞标本中高表达,恶性胸水肺腺癌细胞中PTN蛋白的表达高于血清中PTN蛋白的表达,肺腺癌细胞中PTN蛋白的表达与波形蛋白Vimentin表达相一致,肺腺癌细胞在转移过程中已发生了向间质细胞转化EMT的过程,同时增强了肺腺癌细胞的高侵袭性,而恶性胸水肺腺癌细胞PTN蛋白的高表达更促进了肺腺癌细胞的转移.提示对未发生胸水转移的肺腺癌患者进行血清中PTN蛋白的检测,对已发生胸水转移的肺腺癌患者同样要检测PTN蛋白,以期提高肺腺癌患者的诊断率.     

Slug和E-cadherin在非小细胞肺癌恶性胸水细胞中的表达变化

目的研究锌指转录因子Slug、E-cadherin和Vimentin在非小细胞肺癌恶性胸水细胞中的表达。方法应用免疫细胞化学和western blot检测Slug、E-cadherin和Vimentin在非小细胞肺癌胸水中的表达。结果在121例非小细胞肺癌胸水中,Slug、E-cadherin和Vimentin的阳性表达率分别为35.5%(43/121)、71.9%(87/121)和39.71%(48/121),在非小细胞肺癌细胞中Slug和E-cadherin阳性表达率均高于正常胸水,Slug表达的增强通常伴随E-cadherin表达下调及Vimentin表达的增强。结论 Slug与E-cadherin在胸水中非小细胞肺癌细胞中的表达呈负相关,在胸水中提取非小细胞肺癌细胞,研究Slug和E-cadherin,Vimentin的表达及其在上皮间质转化中的调节作用对探讨肿瘤细胞在人体中的转移进展很有意义。     

肺腺癌细胞中EGFR蛋白的表达与细胞内胶原化的相关性研究

目的探讨表皮生长因子受体（epidermal growth factor receptor,EGFR）在肺腺癌细胞中的表达及与细胞发生胶原化的相关性。方法从胸水中提取肺腺癌细胞为研究对象,以32例良性胸水中的增生上皮细胞、炎性细胞为对照,采用免疫细胞化学方法检测细胞中EGFR、E钙粘素蛋白、Vimentin、TTF-1和胶原蛋白亚型I的表达。Masson染色方法检测胶原纤维表达。结果78例胸水标本中,EGFR在肺腺癌细胞中的阳性率为79．5％,胶原蛋白亚型I为32．1％,Masson染色的阳性率为70．5％,明显高于对照组且EGFR和Masson染色的阳性表达结果的相关性具有统计学意义（P〈0．01）。结论EG—FR在肺腺癌细胞中阳性表达,可能与细胞内基质胶原蛋白形成有关。     

缺氧诱导因子-1在非小细胞肺癌胸水中的表达及其与肿瘤血管生成的关系

目的探讨缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)在非小细胞肺癌胸水细胞中的表达及其与肿瘤血管生成的关系。方法利用免疫组织化学、免疫细胞化学分别检测1180例非小细胞肺癌标本中HIF-1α和HIF-1β蛋白的表达以及非小细胞肺癌胸水细胞中血管生成标记物CD34和VEGF的表达情况,其中包括1060例非小细胞肺癌胸水标本以及用于对照的120例肺穿刺非小细胞肺癌组织标本。结果 HIF-1α在非小细胞肺癌穿刺组织中的表达率72.50%(87/120)明显高于非小细胞肺癌胸水中表达率17.55%(186/1060),差异有统计学意义(P0.05);HIF-1β在非小细胞肺癌穿刺组织中的表达率为77.50%(93/120),而在非小细胞肺癌胸水中表达率为81.42%(863/1060),差异无统计学意义(P0.05);CD34、VEGF在非小细胞肺癌胸水细胞中阳性表达率分别为77.92%(826/1060)、82.92%(879/1060)。HIF-1α与HIF-1β的表达呈显著正相关(r=0.093,P=0.002),HIF-1α与VEGF的表达呈显著正相关(r=104,P=0.001),HIF-1β与VEGF的表达无相关性(P0.05)。结论 HIF-1α在非小细胞肺癌穿刺组织与非小细胞肺癌胸水中的差异性表达,可能与非小细胞肺癌胸水细胞缺氧适应性调节有关,HIF-1与肿瘤血管生成密切相关。     

MMP-2 VEGF在肺腺癌细胞中的表达及其意义

目的研究探讨基质金属蛋白酶2(MMP-2)及血管内皮生长因子(VEGF)在胸腔积液、痰液中肺腺癌细胞的不同表达及二者在肺癌细胞侵袭转移过程中的相互关系。方法选择胸腔积液、痰液共计264例癌性及异型增生细胞标本经免疫细胞化学方法分别检测MMP-2 VEGF的表达情况。结果免疫细胞化学结果显示:MMP-2在胸腔积液中腺癌细胞、异型增生上皮细胞的表达率分别为71.7%(99/138)、16.7%(6/36),在胸膜炎和结核病变典型良性胸腔积液增生上皮细胞中不表达;在痰腺癌细胞中的表达率为39.1%(27/69),统计结果显示MMP-2在恶性胸腔积液腺癌细胞中的表达率明显高于在异型增生的上皮、增生的上皮及痰腺癌细胞的表达率(P均0.05)。VEGF在胸腔积液中腺癌细胞、异型增生上皮细胞的表达率分别为89.1%(123/138)、33.3%(12/36),在胸膜炎和结核病变典型良性胸腔积液增生上皮细胞中不表达;在痰腺癌细胞中的表达率为47.8%(33/69),VEGF在恶性胸腔积液腺癌细胞中表达率明显高于在异型增生的上皮细胞、增生的上皮细胞及痰腺癌细胞的表达率(P均0.05),且MMP-2同VEGF总阳性表达率之间成正相关(r=0.867,P=0.049)。结果 MMP-2 VEGF在胸水腺癌细胞中高表达,可能与肺腺癌的转移、侵袭有关;两者联合做免疫细胞化学检查对肺腺癌细胞病理诊断有辅助意义。     

联合抗体免疫组织化学检测胸水细胞对恶性间皮瘤诊断的应用价值分析

目的探讨在胸水沉渣包埋切片中,应用免疫组织化学技术诊断恶性间皮瘤时,联合抗体套餐的最佳选择。方法对523例胸水标本进行液基学检测,并对其中诊断结果为恶性间皮瘤的63例及肺腺癌的52例胸水标本进行离心沉渣后包埋、切片,采用免疫组织化学方法检测细胞角蛋白5/6(CK5/6)、细胞角蛋白7(CK7)、甲状腺转录因子-1(TTF-1)、波形蛋白(Vim)、P53、间皮细胞(MC)抗体、钙视网膜蛋白(CR)、表皮生长因子受体(EGFR)、E-钙粘蛋白(E-cad)、癌胚抗原(CEA)的表达,比较这些抗体的阳性表达率,特异性及敏感性,探讨诊断恶性间皮瘤联合抗体的最佳套餐选择,同时对临床较常见的粘液型及乳头状型恶性间皮瘤组化结果进行比较,分析恶性间皮瘤的形态学分型对免疫组化结果有否影响。结果在63例恶性间皮瘤患者中,CK5/6、MC、CR、EGFR、Vim的阳性表达率较高,在52例肺腺癌患者中,TTF-1和CEA的阳性率表达率最高;CK5/6、MC、CR、EGFR、Vim TTF-1、CEA特异性和(或)敏感性较高。结论诊断恶性间皮瘤的最佳联合抗体套餐选择为CK5/6、MC、CR、EGFR、Vim、TTF-1、CEA;粘液型及乳头状型恶性间皮瘤抗体阳性表达率无明显区别。     

Egfl7 与非小细胞肺癌上皮间质转化关系的研究

目的:研究Egfl7与非小细胞肺癌(NSCLC)上皮间质转化标志物E-cadherin,Vimentin的相关性,探讨Egfl7是否参与NSCLC的上皮间质转化(EMT)。方法:分别采用免疫组化法和RT-PCR法检测40例NSCLC组织和20例肺癌旁正常肺组织中Egfl7,E-cadherin和Vimentin蛋白和mRNA的表达情况。结果:1).NSCLC组织中的Egfl7蛋白和mRNA的表达水平明显高于癌旁正常肺组织;其差异有统计学意义(P<0.05)。Egfl7的表达水平与肺癌的临床分期、及淋巴结转移密切相关(p0.05)。结论:NSCLC组织中Egfl7高表达,Egfl7可能与NSCLC的侵袭性相关;Egfl7与E-cadherin呈负相关,与Vimentin表达成正相关,Egfl7可能参与了NSCLC患者的上皮间质转化(EMT)过程,阻断Egfl7信号可能会抑制NSCLC患者的ENT。     

Nucleostemin与MDM2在肺腺癌组织中的表达及意义

核干细胞因子(Nucleostemin,NS)是细胞增殖的调节因子,在肺腺癌组织中的表达及与鼠双微染色体2(murine double minute 2,MDM2)表达的相关性不清楚.通过反转录聚合酶链反应(RT-PCR)检测22对肺腺癌和癌旁正常组织NS mRNA的表达;应用免疫组织化学SP法检测45例肺腺癌和22例癌旁正常组织NS与MDM2蛋白的表达,分析其相关性及意义.研究发现,肺腺癌组织中NS mRNA的相对表达强度明显高于癌旁正常组织(P0.01).NS和MDM2蛋白在肺腺癌组织中的阳性表达率分别为73.3%(33/45)、57.8%(26/45),而癌旁正常组织中无阳性表达(P0.01).二者的阳性表达均与组织学分级相关(P0.05),并且表达呈正相关(P0.05),而与患者性别、年龄、肿瘤大小、TNM分期及淋巴结转移无关(P0.05).结果表明NS基因的高表达对肺腺癌细胞的恶性增殖发挥了重要作用,可能是通过p53通路对细胞周期影响所实现的.     

脑脊液中转移性腺癌细胞免疫表型的变化

目的探讨脑脊液中转移腺癌细胞在没有血供的条件下的生长特征,是否有血管内皮标记物CD34,CD105,FⅧ,淋巴管内皮标记物D2_40及碱性成纤维生长因子(b-FGF)的表达,并促进肺癌的脑转移及肿瘤细胞自我生存的调控。方法采集109例腺癌脑转移患者的脑脊液为研究对象,其中肺癌脑转移107例(包括49例肺癌术后5年内脑转移,58例无肺癌病史直接经脑脊液穿刺发现肺癌脑转移),乳腺癌2例。以40例主要成分为炎性细胞的脑脊液及40例原发性肺腺癌组织标本为对照,采用免疫化学染色方法检测脑转移腺癌细胞及腺癌组织中CD34,CD105,FⅧ,D2_40,b-FGF,VEGF及vimentin的表达。结果 109例脑脊液标本中,CD34,CD105,FⅧ,D2_40,b-FGF及VEGF在转移癌细胞中的阳性率分别为64.2%,67.9%,66.9%,63.8%,56.8%,70.6%明显高于脑脊液对照组(阳性率均为0)且差异具有统计学意义(P0.05)。vimentin在脑脊液转移腺癌细胞中阳性表达,表达率为88.1%。在原发肺癌标本中,CD34,CD105,FⅧ和VEGF表达较弱或不表达。D2-40在癌中不表达。B-FGF与Vimentin在原发肺腺癌中的表达率分别为50.1%和29.3%。结论在肺癌脑转移过程中,肿瘤细胞能够表达不同的血管生长因子,提示可能具备内皮细胞的生物学特性,可能有助于增强肿瘤细胞的转移能力和对环境的耐受能力。     

EGFR在晚期肺腺癌患者中的表达及临床意义

目的探讨表皮生长因子受体(EGFR)在晚期肺腺癌患者中的表达及其意义。方法收集60例晚期肺腺癌患者的胸腔积液及活检肺癌组织,采用免疫组化检测EGFR的表达,并探讨其表达与临床病理特征的关系。结果 EGFR在胸腔积液及肺癌组织中的阳性表达率分别为75.0%(45/60)、63.3%(38/60),两者差异无统计学意义(P0.05)。结论 EGFR均高表达于肺腺癌胸腔积液及腺癌组织,且与年龄、性别、吸烟史、分化程度及肿瘤的大小无明显相关,可指导肺腺癌患者的靶向治疗。     

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.     

Serum pleiotrophin as a diagnostic and prognostic marker for small cell lung cancer

Pleiotrophin (PTN) is involved in tumour progression, angiogenesis and metastasis. The purpose of this study was to investigate the expression level of PTN in the serum of patients with small cell lung cancer (SCLC) and to explore the clinical significance of PTN. Serum samples from 128 patients with SCLC, 120 healthy volunteers (HV) and 60 patients with benign lung disease (BLD) were collected. The levels of serum PTN were determined with ELISA and its correlation with the clinical data was examined. The serum PTN levels in SCLC patients were significantly higher than that in BLD patients (P < 0.05) or HV (P < 0.05). With a cutoff value of 258.18 ng/mL, the sensitivity and specificity of PTN to SCLC patients and BLD patients, SCLC patients and HV were 79.2% and 91.7%, 86.7% and 95.8% respectively. An area under the curve for all stages of SCLC resulting from PTN, which was significantly better than the other tumour markers tested including progastrin‐releasing peptide and neuron‐specific enolase. High serum PTN levels appear to correlate with poor survival in patients with SCLC. These results suggest that PTN levels in the serum could be a new effective biomarker for the diagnosis and prognosis of SCLC.     

Elevated expression of pleiotrophin in human hypertrophic scars

Hypertrophic scar (HS) is a cutaneous fibrotic disorder characterized by persistent inflammation, excessive proliferation of fibroblasts, and abundant accumulation of extracellular matrix (ECM) proteins. Pleiotrophin (PTN) is a highly conserved and secreted ECM-associated protein that belongs to a novel family of heparin-binding cytokines with multiple biological functions. The aim of this study was to detect and compare the expression and localization of PTN in HS tissues and normal skin tissues. Surgically removed HS tissue samples and site-matched normal skin specimens were obtained from 18 patients during the scar excision and reconstructive surgery. Semi-quantitative RT-PCR, Western blot analysis and immunohistochemistry were used to determine PTN gene expression and localization in skin tissues. Compared with the normal skin tissues, PTN was highly expressed at both mRNA and protein levels in HS tissues (P < 0.01). In immunohistochemical staining, PTN protein was localized in the cells of both epidermis and dermis in skin tissues, and there were increased staining intensity of PTN in HS tissues than in normal skin samples. In conclusion, elevated expression of PTN is likely to be involved in the pathogenesis of HS. Further studies are still required to elucidate the exact role of PTN in HS formation.     

肺癌患者血清CEA、CYFRA21-1和NSE的检测及临床意义

目的探讨外周血癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和神经元特异性烯醇化酶(NSE)的检测对肺癌的诊断、病理分型和疗效判断的临床用价值。方法采用化学发光法检测了62例肺癌患者、54例良性肺部疾病患者、36例健康人、40例肺癌患者手术前后血清CEA、CYFRA21-1和NSE的水平。结果肺癌患者手术前血清CEA、CYFRA21-1和NSE的含量明显高于良性肺部疾病组及正常对照组(P0.01)。鳞癌组、腺癌组和小细胞癌组之间肿瘤标志物CEA、CYFRA21-1和NSE水平差异有统计学意义。CEA阳性率以腺癌组最高(84%),CYFRA21-1阳性率以鳞癌组最高(85.2%),NSE阳性率以小细胞癌组最高(80.0%)。手术治疗后未复发转移组CEA、CYFRA21-1和NSE水平低于术前,而复发转移组与术前比变化不显著(P0.05)。结论血清CEA、CYFRA21-1和NSE的检测对不同病理类型肺癌患者的诊断、病情检测及疗效判断有较好的临床参考价值。     

Gene Expression Profiling in Human Lung Development: An Abundant Resource for Lung Adenocarcinoma Prognosis

A tumor can be viewed as a special “organ” that undergoes aberrant and poorly regulated organogenesis. Progress in cancer prognosis and therapy might be facilitated by re-examining distinctive processes that operate during normal development, to elucidate the intrinsic features of cancer that are significantly obscured by its heterogeneity. The global gene expression signatures of 44 human lung tissues at four development stages from Asian descent and 69 lung adenocarcinoma (ADC) tissue samples from ethnic Chinese patients were profiled using microarrays. All of the genes were classified into 27 distinct groups based on their expression patterns (named as PTN1 to PTN27) during the developmental process. In lung ADC, genes whose expression levels decreased steadily during lung development (genes in PTN1) generally had their expression reactivated, while those with uniformly increasing expression levels (genes in PTN27) had their expression suppressed. The genes in PTN1 contain many n-gene signatures that are of prognostic value for lung ADC. The prognostic relevance of a 12-gene demonstrator for patient survival was characterized in five cohorts of healthy and ADC patients [ADC_CICAMS (n = 69, p = 0.007), ADC_PNAS (n = 125, p = 0.0063), ADC_GSE13213 (n = 117, p = 0.0027), ADC_GSE8894 (n = 62, p = 0.01), and ADC_NCI (n = 282, p = 0.045)] and in four groups of stage I patients [ADC_CICAMS (n = 22, p = 0.017), ADC_PNAS (n = 76, p = 0.018), ADC_GSE13213 (n = 79, p = 0.02), and ADC_qPCR (n = 62, p = 0.006)]. In conclusion, by comparison of gene expression profiles during human lung developmental process and lung ADC progression, we revealed that the genes with a uniformly decreasing expression pattern during lung development are of enormous prognostic value for lung ADC.     

结肠癌患者血清及癌组织中VEGF的表达水平及临床意义

目的探讨结肠癌患者血清及癌组织中血管内皮生长因子（VEGF）的表达水平及临床意义。方法选择不同TNM分期的结肠癌患者88例,同时收集因外伤而切除部分结肠组织的患者43例作为对照组,采用酶联免疫吸附法（ELISA）检测不同患者在结肠癌手术前后血清中VEGF水平,利用实时定量PCR,免疫印迹及免疫组织化学染色法测定癌组织及正常对照组中VEGF表达水平,分析VEGF在血清及癌组织中表达水平与临床病理因素相关性。结果 TNM各期结肠癌患者手术前后血清VEGF水平均高于对照组,且差异有统计学意义（P〈0.05）。各期结肠癌患者术前血清VEGF表达高于术后表达水平,差异有统计学意义（P〈0.05）。与对照组相比,结肠癌组织中VEGF表达水平明显高于对照组,差异有统计学意义（P〈0.01）。结论血清及癌组织中VEGF表达水平与结肠癌的临床病理分级及血管浸润呈正相关,有望作为结肠癌病理分级和手术疗效及预后的评价指标。     

过表达BTG2增强人肺腺癌细胞的辐射敏感性

在肺癌类型中,肺腺癌占大多数,其总体生存率差,BTG2是抗增殖基因家族的一员,属于BTG/TOB家族。许多研究表明,B细胞易位基因2(BTG2)多种类型的肿瘤中存在异常表达,但其在肺腺癌放疗敏感性中发挥的调控作用尚不明确。本研究通过肺腺癌组织样本及在线数据库,探究BTG2在肺腺癌患者中的表达水平及其表达与临床预后之间的相关性,结果提示在具有放疗抗性的肺腺癌患者中,BTG2的表达水平显著降低,且在肺腺癌细胞系中,BTG2能对放疗产生响应,其在肺腺癌患者中的低表达状态与不良的预后相关(P＜0.05);在人肺腺癌A549和H1299细胞系中转染过表达BTG2(OE-BTG2)慢病毒,通过克隆形成检测过表达BTG2对肺腺癌细胞系的辐射敏感性的影响,实验证实过表达BTG2可显著增强A549和H1299细胞系的辐射敏感性(P＜0.05);并进一步通过WB、免疫组化检测BTG2及凋亡相关蛋白BAX的表达水平,结果证实:过表达BTG2可显著增加A549和H1299细胞辐射后的凋亡水平。最后通过裸鼠成瘤试验检测BTG2在活体中对肺腺癌辐射敏感性的影响,结果提示:在动物实验中,过表达BTG2可显著增强肺腺癌的辐射敏感性(P＜0.05)及增加辐射后BAX的表达水平。综上所述,BTG2在肺腺癌组织中处于低表达状态,并且与不良的临床预后紧密相关,过表达BTG2可促进凋亡过程,增加人肺腺癌细胞系的辐射敏感性,能为克服肺腺癌的辐射抗性提供新的靶点。     

Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells

Background

Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear.

Methods

We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA.

Results

We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway.

Conclusions

Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

     

Parafibromin expression in lung normal tissue and carcinoma: its comparison with clinicopathological parameters of carcinoma

Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its down-regulated expression is involved in the pathogenesis of parathyroid, gastric and colorectal carcinomas. To clarify the roles of parafibromin expression in lung carcinomas, it was examined by immunohistochemistry and in situ hybridization on tissue microarray containing lung carcinomas (n=144) and normal lung tissue (n=20), with a comparison to clinicopathological parameters of carcinomas. Lung carcinoma cell lines and tissues were studied for parafibromin expression by Western blot and RT-PCR. Down-regulated expression of parafibromin mRNA was found in lung carcinoma in comparison with matched normal tissue (p<0.05). Parafibromin protein was found in the cilia and nuclei of pseudo-stratified columnar epithelium, and the nuclei of lung carcinoma. According to immunostaining and in situ hybridization, there was no difference in parafibromin expression between histological subtypes of lung carcinoma (p>0.05). The Kaplan-Meier method indicated that nuclear parafibromin expression was positively correlated with adenocarcinoma patients (p<0.05). Down-regulated parafibromin mRNA expression might play an important role in lung carcinogenesis, but not in its histogenesis. Strong parafibromin expression in cilia of the pseudo-stratified columnar epithelium indicated its possible involvement in cell mobility. Parafibromin expression could be employed to indicate the favorable prognosis of patients with adenocarcinoma.