非小细胞肺癌组织中FHIT和HER2的表达及其临床意义的研究

目的:探讨FHIT和HER2在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达,及两者的联合表达对判断NSCLC预后和转归的价值。方法:SP法检测90例NSCLC标本中FHIT和HER2的表达。结果:NSCLC组织中FHIT蛋白失表达率53.75%(43/80)显著低于肺良性病变组织的10%(1/10),其失表达率与吸烟(P=0.000)、组织学类型(P=0.004)、淋巴结转移(P=0.002)、pTNM分期(P=0.028)及3年无瘤生存率(P=0.047)存在相关性。HER2蛋白的过表达率62.50%(50/80)却显著高于肺良性病变组织的0(0/10),其过表达率则与淋巴结转移与否(P=0.030)、pTNM分期(P=0.018)及3年无瘤生存率(P=0.028)存在相关性。FHIT蛋白的失表达与HER2蛋白过度表达呈显著负相关,P<0.05。结论:FHIT基因蛋白的失表达和HER2基因蛋白的过表达可能在NSCLC发生和发展过程中起重要作用,并影响预后。     

ＦＨＩＴ和ｍｄｍ２蛋白在非小细胞肺癌中的表达及意义

目的：探讨ＦＨＩＴ和ｍｄｍ２蛋白在非小细胞肺癌（ＮＳＣＬＣ）中的联合表达以及与临床病理特征之间的关系及意义。方法：采用免疫组化法（ＳＰ法）检测ＦＨＩＴ和ｍｄｍ２蛋白在５３例肺癌组织和１９例癌旁正常肺组织的表达情况,并结合肺癌的临床病理特征进行对比分析。结果：５３例肺癌组织ＦＨＩＴ蛋白失表达率６２.２６％,１９例癌旁正常肺组织１００.００％表达ＦＨＩＴ蛋白,二者差异显著（Ｐ＜０.０５）。有吸烟史的ＦＨＩＴ蛋白失表达率为７０.７３％,无吸烟史的为３３.３３％,二者差异显著（Ｐ＜０.０５）。ＦＨＩＴ蛋白失表达率与肺癌的病理类型、细胞分化程度、ｐＴＮＭ分期、淋巴结转移有密切关系（Ｐ均＜０.０５）,而与患者年龄及性别无关（Ｐ＞０.０５）。５３例肺癌组织ｍｄｍ２蛋白过表达率５２.８３％,１９例癌旁正常肺组织均不表达ｍｄｍ２蛋白,二者差异显著（Ｐ＜０.０５）。ｍｄｍ２蛋白过表达率与肿瘤分化程度、ｐＴＮＭ分期、淋巴结转移显著相关（Ｐ＜０.０５）,而与患者年龄、性别、吸烟史及不同的病理类型之间无关（Ｐ＞０.０５）。在ＮＳＣＬＣ中,ＦＨＩＴ与ｍｄｍ２蛋白的表达呈负相关（Ｐ＜０.０５）。结论：ＦＨＩＴ蛋白失表达和ｍｄｍ２蛋白过表达可能促进了肿瘤的恶性增殖及转移,联合检测上述二项指标,可以作为判断非小细胞肺癌的恶性程度、转移潜能以及预后的重要参考。     

Aberrant methylation of the FHIT gene in chronic smokers with early stage squamous cell carcinoma of the lung

Fragile histidine triad (FHIT) gene plays an important role in the pathogenesis of lung cancer. However, the clinicopathological significance of CpG island hypermethylation of FHIT gene in non-small cell lung cancer (NSCLC) remains to be elucidated. We studied FHIT methylation in 254 NSCLCs in order to further understand the clinicopathological and prognostic significance of FHIT methylation in NSCLC. Methylation status of the FHIT gene was examined using Methylation-Specific PCR. All statistical analyses were two-sided, with a 5% type I error rate. Hypermethylation of the FHIT gene occurred more frequently in squamous cell carcinoma than adenocarcinoma. For 93 adenocarcinomas there was no statistically significant association between FHIT methylation and age, gender, smoking history, pathologic stage and p16 methylation. However, FHIT methylation in 125 squamous cell carcinomas was associated with exposure to tobacco smoke and p16 methylation, but not with age, gender and pathologic stage. Hypermethylation of FHIT in squamous cell carcinomas occurred more frequently in current smokers (45%) than in never-smokers (13%). FHIT methylation was significantly associated with p16 methylation in current- and ex-smokers (P = 0.02 and P = 0.01, respectively) with squamous cell carcinoma and in patients with pathologic stage I squamous cell carcinoma (P = 0.001). Patients with p16 methylation were 3.74 times [95% confidence interval (CI) = 1.62 - 7.95; P = 0.001] more likely to have FHIT methylation in squamous cell carcinoma. FHIT methylation in squamous cell carcinoma occurred at a 4.62 times (95% CI = 1.26 - 34.97; P = 0.02) higher prevalence in current smokers than in never-smokers. No prognostic effect of FHIT methylation was observed in stage I and stage II NSCLCs. In conclusion, hypermethylation of the FHIT gene did not have a prognostic significance in early stage NSCLCs. The FHIT methylation is associated with the p16 methylation and smoking in squamous cell carcinoma, suggesting that FHIT may cooperate with p16 for the development of squamous cell carcinoma of lung in individuals exposed to tobacco smoke.     

脆性组氨酸三联体基因及p53 基因在肺癌组织中的表达及意义

 目的 探讨脆性组氨酸三联体基因（FHIT）在肺癌组织中的表达及其与肺癌分化程度、组织学分类、p53表达的关系。方法 利用组织芯片，运用免疫组织化学技术，对110例肺癌及25例良性病变的肺组织标本分别进行FHIT、p53蛋白检测。结果 ①良性病变肺组织FHIT异常表达率为16％，而肺癌组织中FHIT异常表达率为85．5％。肺癌组织与良性病变肺组织相比，差异有极显著性（P〈0．01）；分化程度不同肺癌组织，FHIT表达差异有极显著性（P〈0．01），且FHIT基因表达与肺癌组织分化程度正相关（P〈0．01）；组织学分类不同的肺癌组织，FHIT基因表达差异无统计学意义（P〉0．05）；②p53阴性表达组和阳性表达组，FHIT的表达差异无统计学意义（P〉0．05）；p53异常表达率为53．6％，FHIT异常表达率为85．4％，两者比较差异有极显著性（P〈0．01）。p53异常表达与FHIT异常表达共同检出率为93．6％。结论 ①FHIT蛋白可能成为肺癌早期诊断的更有效分子标记物，p53蛋白与FHIT蛋白的联合检测有助于提高肺癌的检出率；②FHIT蛋白影响肺肿瘤细胞的分化方向，为临床药物开发提供新思路。     

FHIT和p53在原发性肺癌中的表达及其与淋巴结转移的关系

目的探讨原发性肺癌组织中FHIT和p53蛋白表达及其与淋巴结转移的关系。方法采用S-P免疫组织化学技术及HE染色,对FHIT和p53蛋白表达进行观察。结果57例原发性肺癌中淋巴结转移32例,转移率为56.1%。其中FHIT阴性表达者,淋巴结转移率显著高于阳性表达（P〈0.05）,呈负相关,而p53则以阳性表达者淋巴结转移率明显高于阴性表达者（P〈0.05）,呈正相关。结论FHIT和p53检测不仅对肺癌治疗有重要的参考价值,而且对肺癌有无淋巴结转移的判断及预后的估计确有较大的参考价值。     

脆性组氨酸三联体基因在宫颈癌前病变和宫颈癌中的表达及其与p53和HPV16/18的关系

目的 探讨脆性组氨酸三联体（FHIT）基因缺失与p53的过度表达和人乳头状瘤病毒16和（或）18（HPV16／18）感染在宫颈癌前病变（CIN）和宫颈癌（CC）发生发展中的作用和意义。方法 采用免疫组化SP法检测52例CIN和69例CC中的FHIT基因和p53的表达,以原位杂交方法检测HPV16／18感染情况,并以18例正常宫颈组织作为对照。结果 FHIT在正常宫颈组织（正常组）中呈阳性表达;FHIT在宫颈CIN组中的阴性率为30．8％,在CINⅢ期的表达,明显高于正常组和CINⅠ、Ⅱ期（P〈0．01）;在CC组中阴性率为66．7％（46／69）,明显高于正常组和CIN组（P〈0．01）,且随细胞分化的降低,FHIT阴性率上升。p53和HPV16／18在CC组的阳性率分别达56．5％（39／69）和84．1％（58／69）,均高于CIN和正常组（P〈0．05）,且CC组的p53阳性率随细胞分化的降低而升高（P〈0．01）。CIN和CC组的FHIT阳性和阴性者,p53阳性率差异均无统计学意义（P〉0．05）,相关性分析也显示无相关关系;但两组FHIT阴性者的HPV16／18感染率明显高于FHIT正常表达者（P〈0．01）,FHIT与HPV呈负相关关系。结论 FHIT基因缺失与宫颈癌发生有关,它在CIN中的缺失可能可作为高危型CIN人群的筛选和宫颈癌早期诊断指标。CIN和CC中的FHIT缺失常与p53过度表达同时存在,但两者间无相关性。HPV16／18可能是引起FHIT和p53异常的共同原因。     

脆性组氨酸三联体与肺癌的临床病理学研究

目的:探讨抑癌基因FHIT在肺癌组织中的表达缺失及其与临床病理因素的关系.方法:采用免疫组织化学S-P法检侧40例肺癌组织中FHIT蛋白表达情况,以癌旁组织作对照.结果:FHIT蛋白表达阴性率在肺癌为65.00%(26/40),FHIT蛋白在肿瘤组织中的表达明显低于癌旁正常组织(P<0.05).其中鳞癌为38.46%(5/13),腺癌为77.78%(21/27),其差异有显著性(P=0.01).FHIT与组织学类型、分化程度及性别有相关性(P<0.05).与年龄、肿瘤大小、临床分期、有无淋巴结转移无关(P>0.05).结论:FHIT在肺癌中失表达或表达下降可能与肺癌的发生有相关性.     

Reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients.

The FHIT gene, at 3p14.2, has been suggested to form a molecular target to damage induced by human lung carcinogens. We examined aberrant expression of the Fhit protein and allele loss at the FHIT gene in a series of lung cancer cases, mainly of non-small cell carcinoma (NSCLC) histology. We had detailed data on tobacco smoke exposure and occupational asbestos exposure available for the cases. The principal aim of the present study was to investigate whether absent or reduced Fhit expression or FHIT allele loss was associated with exposure to these pulmonary carcinogens. We detected reduced Fhit expression in 62% (33/53) of the cases analysed. Prevalence of allele loss at the FHIT locus was 22% (20/89). Reduced protein expression was common both in the asbestos-exposed (67%) and non-exposed cases (59%); [odds ratio (OR) 1.4, 95% confidence interval (CI) 0.4-4.9]. LOH frequencies differed somewhat between the two groups and were 25% vs. 16%, respectively (OR 1.8; 95% CI 0.5-5.9). Absent or reduced expression was common in smokers, with no significant difference found between current smokers and non-smokers (mainly former smokers) (OR 1.4, 95% CI 0.5-4.5). NSCLCs with squamous cell histology exhibited both aberrant expression (OR 3.1, 95% CI 0.9-10.3) and allele loss (OR 3.3, 95% CI 0.9-12.7) more frequently than adenocarcinoma. Finally, we found that FHIT allele loss was increased in stage II or more advanced disease (OR 2.5, 95% CI 0.9-7.4), and in poorly differentiated tumours (grade 3, OR 2.6, 95% CI 0.8-8.1). In conclusion, our present data support significance of FHIT inactivation in development of lung cancer.     

非小细胞肺癌组织中FHIT和p16基因表达的研究

背景与目的:探讨FHIT和p16基因在非小细胞肺癌(NSCLCs)中的表达及其与临床病理因素的关系.材料与方法:采用免疫组化SP法检测80例NSCLCs组织中FHIT和p16的表达.结果:在80例NSCLCs组织中,54例(67.5%)显示FHIT表达下降或缺失;63例(78.75%)p16蛋白表达下降.FHIT蛋白的表达异常与性别和组织学类型相关,而p16蛋白表达下降与肿瘤的淋巴结转移之间有相关性.结论:FHIT和p16蛋白异常表达分别与NSCLCs的性别、组织学类型及淋巴结转移相关,提示可能对肺癌的演变和进展具有重要作用.     

Frequent allelic deletion at the FHIT locus associated with p53 overexpression in squamous cell carcinoma subtype of Taiwanese non-small-cell lung cancers

The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a tumour suppressor gene involved in different tumour types including non-small-cell lung cancers (NSCLCs). In the current study, we examined for allelic deletion at the FHIT locus in 58 primary and microdissected NSCLCs, for which a clinicopathologic profile was available. We found a loss of 87.7% in heterozygosity (LOH) frequency at one or more microsatellite markers (D3S1289, D3S2408, D3S1766, D3S1312, D3S1600). Allelic deletion of D3S1766 was related to tumour histology in 10 of 11 squamous cell carcinomas (90.9%) displaying LOH compared with nine of 17 adenocarcinomas (52.9%; P=0.049). Besides, in the subset of adenocarcinomas, a higher rate of LOH at D3S1289 was observed in male (six out of eight, 75%) than in female patients (four out of 17, 23.5%; P=0.028). However, FHIT LOH was not correlated overall with a variety of clinical parameters including sex, smoking status, staging, lymph node metastasis and survival. These results indicated that the high frequency of FHIT gene disruption was important in the development of both squamous cell carcinomas and adenocarcinomas. Furthermore, there was no association between LOH at FHIT and protein expression, suggesting the presence of complex mechanisms of Fhit inactivation. On the other hand, the association between FHIT LOH and p53 protein overexpression assessment reached statistical significance (P=0.026), implying that common alterations affect the two genes in tumour progression.     

Loss of heterozygosity at loci of candidate tumor suppressor genes in microdissected primary non-small cell lung cancer

To investigate the etiological association of allelic loss at chromosomal regions containing tumor suppressor genes (TSGs) in non-small cell lung cancer (NSCLC) in Taiwan, we examined 48 microdissected NSCLC samples for loss of heterozygosity (LOH) at nine loci where TSGs are localized nearby. The associations of LOH at each locus with clinicoparameters and prognosis were also examined. The frequent LOH was observed using markers, D3S1285 near the FHIT gene (58.3%), D17S938 near the p53 gene (56.7%), D9S925 near the p16 gene (54.5%), and D13S153 near the RB gene (47.6%). The occurrence of LOH at each TSG locus was compared with the patients' clinicoparameters. The incidence of LOH at D17S938 (p53 gene) and D3S4545 (VHL gene) was significantly higher in squamous carcinoma tumors than in adenocarcinoma tumors (P = 0.003 and 0.024, respectively). LOH of these two loci also occurred frequently in tumors from smoker patients compared to that from nonsmoker patients (P = 0.013 and 0.025, respectively). LOH at D13S153 (RB gene) was also associated with smoking (P = 0.008). In addition, the prognostic analyses indicated that the patients with LOH at D18S535 (18q21, near the SMAD2/4 gene) had significantly longer post-operative survival time compared to those without LOH (P = 0.03). Our results suggested that LOH at FHIT, p53, and p16 genes may occur frequently in NSCLC patients in Taiwan. In addition, LOH at p53, RB, and VHL may associate with smoking or squamous carcinoma patients and LOH at SMAD2/4 may be correlated with better prognosis.     

5' cytosine-phospho-guanine island methylation is responsible for p14ARF inactivation and inversely correlates with p53 overexpression in resected non-small cell lung cancer.

PURPOSE AND EXPERIMENTAL DESIGN: The molecular mechanisms by which the p14ARF gene is altered in non-small cell lung cancer (NSCLC) are complex and unclear. Using genetic and epigenetic analyses, we examined various molecular alterations including the loss of protein and mRNA expression, and 5'CpG hypermethylation, allelic imbalance, and mutation of the p14ARF gene in a series of 102 NSCLC samples, in parallel with clinicopathological and prognostic analyses. To clarify the biological significance of p14ARF alterations, its relationship with p16INK4a and p53 alterations was also examined. RESULTS: We found that 34% of NSCLC patients had aberrant P14ARF protein expression, which was more frequent in adenocarcinomas (AD; 44%) than in squamous cell carcinomas (22%; P = 0.024). A high concordance was observed between alterations in protein and mRNA expression and 5'CpG hypermethylation (P 相似文献   

Cyclin D1 expression in non-small-cell lung cancers: its association with altered p53 expression, cell proliferation and clinical outcome.

Cyclin D1, like p16INK4 (p16) and retinoblastoma (RB) proteins, participates in the cell cycle control at the G1-S transition. We have previously demonstrated altered p16 and RB protein status in non-small-cell lung cancers (NSCLCs) and their potential synergistic effect with altered p53 protein on proliferative activity (Kinoshita et al (1996) Cancer Res 56: 5557-5562). In the present study, cyclin D1 expression was studied by immunohistochemistry in the same cohort of 111 resected NSCLCs as in our previous study, and the amount of the cyclin D1 gene was analysed by Southern blot analysis in 29 NSCLCs. Cyclin D1 expression was analysed in relation to the status of p53, p16 and RB proteins, and proliferative activity determined by the Ki-67 index. It was also analysed in relation to survival of 77 patients with NSCLCs which were potentially curatively resected between 1990 and 1995. We found that: (1) cyclin D1 was expressed in 13 (11.7%) of 111 NSCLCs; (2) the cyclin D1 gene was neither significantly amplified nor rearranged; (3) cyclin D1 expression significantly correlated with altered p53 protein expression (P = 0.04), whereas it did not correlate with p16 and RB protein status; (4) proliferative activity tended to be higher in cyclin D1-positive (+) tumours than in cyclin D1-negative (-) tumours, although this difference was not statistically significant (P = 0.08); and (5) patients with cyclin D1+ tumours survived longer than patients with cyclin D1- tumours (5-year survival rates, 89% and 64% respectively, by the Kaplan-Meier method; P = 0.045 by the log-rank test), and cyclin D1 expression tended to be a favourable prognostic factor (P = 0.08 in univariate analysis). These findings suggest the involvement of cyclin D1 in the development and progression of NSCLCs, their proliferative activity and clinical outcome of NSCLC patients.     

肺癌前病变、肺癌中FHIT基因表达的临床研究

背景与目的FHIT基因为近年发现的新的候选抑癌基因，位于3p14．2，跨越FRA3B易脆点，在包括肺癌在内的多种人类肿瘤中均存在异常表达。本研究旨在观察FHIT基因在人肺癌前病变、肺癌中的表达情况，探讨FHIT基因在肺癌发生、发展过程中的可能作用。方法采用免疫组化方法检测298例甲醛固定、石蜡包埋的标本（包括161例肺癌、51例肺癌前病变、30例正常肺组织、23例肺良性病变和33例肺癌转移淋巴结）中FHIT蛋白表达情况。结果FHIT蛋白在正常肺组织及肺良性病变组织中均无失表达，癌前病变组织和肺癌组织中失表达率分别为54．9％（28／51）和59．0％（95／161），肺癌转移淋巴结组织中失表达率为78．8％（26／33）；肺癌前病变、肺癌及转移淋巴结组织中FHIT蛋白失表达率显著高于正常肺组织及肺良性病变组织（P〈0．001）。肺癌组织中FHIT基因表达水平与肺癌组织学类型、肿瘤细胞分化程度、患者pTNM分期、淋巴结转移有密切关系（P〈O．05）。FHIT蛋白失表达组肺癌患者的术后5年生存率显著低于表达组（P〈0．01）。吸烟组患者FHIT基因失表达率69．1％显著高于无吸烟组49．5％（P〈0．01）。结论FHIT蛋白失表达可能是肺癌发生过程中的早期分子事件，与肺癌的发生、发展及预后有关；吸烟导致FHIT蛋白表达下降可能是诱发肺癌的原因之一。     

人非小细胞肺癌组织p63和p73的表达及意义

目的 :探讨p5 3家族新成员p6 3和p73在非小细胞肺癌 (NSCLC)中的表达及其临床意义。方法 :利用免疫组化S P法对 6 0例NSCLC和 7例正常肺组织检测p6 3和p73基因的蛋白表达。结果 :在NSCLC中 ,p6 3和p73蛋白表达的阳性率分别为 80 0 % (4 8/ 6 0 )、73 3% (4 4/ 6 0 ) ;与正常肺组织相比 ,p6 3和p73蛋白阳性表达的差异均有显著意义 ,P <0 0 5。p6 3蛋白表达与肺癌组织学类型 (P =0 0 0 0 3)和淋巴结转移有关 ,P =0 0 2 8;而与分化程度和临床分期无关 ,P >0 0 5。p73蛋白表达与肺癌组织学类型、淋巴结转移、分化程度和临床分期均无关 ,P >0 0 5。在肺癌中 ,p6 3蛋白和p73蛋白表达之间呈显著正相关 ,P =0 0 0 0 1。结论 :p6 3和p73高水平的表达协同促进肺癌的形成 ,p6 3是肺鳞癌恶性进展的一个标志物。     

p53、Cyclin D1及PCNA在非小细胞肺癌的表达

目的 研究非小细胞肺癌（NSCLC）中p53、Cyclin D1蛋白表达及与细胞增殖的关系。方法 应用免疫组织化学技术（SP法）检测74例NSCLC中p53、Cyclin D1蛋白和增殖细胞抗原（PCNA）的表达情况。结果 p53蛋白、CyclinD1蛋白在NSCLC中阳性表达率分别为55．41％和37．84％,均明显高于正常肺组织（P1＝0．0031,P2＝0．0429）。 p53蛋白表达与淋巴结转移有密切关系（P＝0．0222）。p53蛋白、CyclinD1蛋白表达分别与PCNA指数有密切关系（P1＝0．001,P2＝0．0009）。p53蛋白与CyclinD1蛋白表达之间未见明显关系（P＞0．05）。结论 p53蛋白和CyclinD1蛋白近表达参与了NSCLC的发生发展,有促进细胞增殖的作用。p53的诊断和评价NSCLC预后的重要参数。     

Cohypermethylation of p16 and FHIT promoters as a prognostic factor of recurrence in surgically resected stage I non-small cell lung cancer

Despite advances in the detection and treatment of lung cancer, the prognosis for patients with lung cancer is poor, partly as a result of recurrences. We retrospectively analyzed the relationship between recurrence and survival in patients with non-small cell lung cancers (NSCLC), and the promoter methylation of p16, GSTP1, FHIT, H-cadherin, and RARbeta2 genes to identify a prognostic molecular marker associated with the recurrence of NSCLC. Methylation status from 335 paraffin blocks was determined by methylation-specific PCR. Of the 335 NSCLC samples, promoter methylation was detected in 35% for p16, 39% for RARbeta2, 42% for H-cadherin, 7% for GSTP1, and 21% for FHIT. Recurrence was observed in 39% (132 of 335) of the patients. Recurrence was significantly associated with histology (P = 0.001) and pathologic stage (P = 0.009). Hypermethylation of any single gene was not associated with recurrence in patients. However, cohypermethylation of p16 and FHIT genes in stage I NSCLCs was associated with an increased risk of recurrence [odds ratio, 6.43; 95% confidence interval (CI), 1.04-20.19; P = 0.02] and poor recurrence-free survival after surgery (hazard ratio, 2.03; 95% CI, 1.09-6.23; P = 0.02). In addition, their survival after recurrence was also 4.62 times poorer (95% CI, 1.27-16.48; P = 0.005) than for those without cohypermethylation of both genes. In conclusion, the present study suggests that cohypermethylation of p16 and FHIT genes in patients with stage I NSCLC may be a valuable biomarker for predicting the recurrence-associated prognosis of the disease.     

非小细胞肺癌组织p53和c-erbB2及MRP蛋白的表达

目的探讨癌组织p53、c-erbB2、MRP蛋白表达与非小细胞肺癌（NSCLC）临床病理特征的关系及其预后评估意义。方法应用免疫组织化学方法检测NSCLC患者的肺组织切除标本p53、c-erbB2、MRP蛋白表达,并与其临床病理参数进行比较分析。结果NSCLC组织p53、c-erbB2、MRP蛋白表达阳性率分别为53.9%（82/152）、44.1%（67/152）及43.4%（66/152）。p53表达与性别、细胞分化程度、临床分期、淋巴结转移有显著关系（P〈0.05）,而c-erbB2与各因素间无统计学差异,肺腺癌MRP蛋白表达阳性率（67.6%）明显高于肺鳞癌（33.0%）,有统计学差异（P〈0.05）。癌组织p53、c-erbB2、MRP 3种蛋白表达均阳性者的1、2、3年生存率明显低于均阴性者（分别P=0.02、0.01和0.00）,p53、c-erbB2、MRP蛋白表达阳性者单纯手术后生存率也明显低于阴性者（P〈0.05）;p53、c-erbB2、MRP 3种蛋白表达均阴性者预后最好,1-2种阳性者次之,3种均阳性者预后最差（P〈0.05）。术后辅助化疗组MRP、c-erbB2蛋白表达阳性者的生存率低于阴性者（P〈0.01）,但p53蛋白表达阳性与阴性患者的生存率无统计学差异（P=0.82）;MRP与c-erbB2表达双阴性者生存率显著高于双阳性者,MRP或c-erbB2单一阳性的生存率介于前两者之间（P=0.01）。多因素Cox分析显示细胞分化程度、c-erbB2是影响NSCLC患者疗效和预后的独立预测因子。结论肿瘤组织p53、c-erbB2、MRP 3种蛋白同时高表达的NSCLC病例预后较差。术后检测p53、c-erbB2、MRP表达对评估可手术NSCLC患者疗效和预后有一定意义。     

脆性组氨酸三联体与肺癌的临床病理学研究

目的：探讨抑癌基因FHIT在肺癌组织中的表达缺失及其与临床病理因素的关系。方法-采用免疫组织化学S—P法检侧40例肺癌组织中FHIT蛋白表达情况,以癌旁组织作对照。结果：FHIT蛋白表达阴性率在肺癌为65．00％（26／40）,FHIT蛋白在肿瘤组织中的表达明显低于癌旁正常组织（P〈0．05）。其中鳞癌为38．46％（5／13）,腺癌为77．78％（21／27）,其差异有显著性（P=0．01）。FHIT与组织学类型、分化程度及性别有相关性（P〈0．05）。与年龄、肿瘤大小、临床分期、有无淋巴结转移无关（P〉0．05）。结论：FHIT在肺癌中失表达或表达下降可能与肺癌的发生有相关性。