Lung cancer in chromate workers: high-risk group for multiple lung cancer

We diagnosed eight (8.9%) lung cancer patients in 90 workers exposed to chromate compounds. The duration of exposure ranged from 8 to 31 years, with a mean value of 18 +/- 8 years. The histological classification was squamous-cell carcinoma in seven patients and adenocarcinoma in one patient. The site of origin of the primary tumors was located peripherally in two (25%) and centrally in six (75%). All but one of these patients underwent surgery. In three (37.5%) of these patients, lung cancer foci were detected during the postoperative follow-up by sputum cytology and bronchoscopy. Two of these three patients had multicentric cancer foci: double primary early squamous-cell carcinoma in one and early squamous-cell carcinoma + small-cell lung cancer in the other. In a high-risk group such as chromate workers, we should emphasize early detection of lung cancer by serial sputum cytology, chest x-rays, and bronchoscopy. Lung cancer patients with chromate exposure should be treated with due regard to the possibility of synchronous or metachronous cancer.     

The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer

STUDY OBJECTIVES: It is known that chromium is one of the important inhaled carcinogens that cause lung cancer. Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). However, the epigenetic effects of chromium are not understood. MATERIALS AND METHODS: We investigated the methylation of the p16 gene using a methylation-specific PCR method in 30 chromate lung cancers and 38 non-chromate lung cancers, and the expression of the p16 protein using immunohistochemistry in 25 chromate lung cancers. RESULTS: Ten (33%) chromate lung cancers showed methylation of the p16 promoter region. On the other hand, 10 (26%) of the non-chromate lung cancers also showed it. The frequency of p16 methylation in non-chromate lung cancer was 0%, 33% and 30% for low (< or =600), moderate (<600, >1000) and high (> or =1000) Brinkman indexes, respectively. However, the frequency of p16 methylation in chromate lung cancer was constant, irrespective of the Brinkman index. In chromate lung cancer, patients with chromate exposure of less than 15 years never had p16 methylation, while 40% (> or =25 years) or 43% (> or =15, <25 years) of patients with chromate exposure of more than 15 years did. In chromate lung cancer, chromate exposure, not smoking, mainly influenced the p16 methylation. Most of the chromate lung cancers with p16 methylation (85.7%) showed repression of the p16 protein. CONCLUSIONS: We speculate that not only genetic but also epigenetic alterations are involved in the carcinogenesis due to chromium.     

Frequent microsatellite instability in lung cancer from chromate-exposed workers

Although chromium has been the most extensively investigated metal with respect to mutagenicity and carcinogenicity, its genetic effects in humans are only partly understood. Our previous study demonstrated that lung cancer from chromate-exposed workers infrequently (20%) displayed p53 gene mutations as well as a particular mutation pattern. In the present study, we examined the replication error (RER) and loss of heterozygosity (LOH) in 38 lung cancers from 28 chromate-exposed workers (chromate lung cancer group) and in 26 lung cancer patients without chromate exposure (non-chromate lung cancer group), using six microsatellite markers containing CA repeats: D3S647 (3p23), D3S966 (3p21.3), D3S1289 (3p21.1), D5S346 (5q21-q22), D9S161 (9p21), and TP53 (17p13.1). The RER phenotype was defined as the presence of microsatellite instability (MSI) at two or more loci. Thirty (78.9%) of 38 tumors in the chromate lung cancer group exhibited RER. In contrast, only four (15.4%) of 26 tumors in the non-chromate lung cancer group exhibited RER. The frequency of RER in the chromate lung cancer group was significantly higher than that in the non-chromate lung cancer group (P < 0.0001). By contrast, the frequency of LOH at 3p, 5q, 9p, and 17p loci in tumors with chromate exposure was not significantly different from that in tumors without chromate exposure. In the chromate lung cancer group, the period of chromate exposure in workers with RER (24.5 +/- 6.7 yr) was significantly longer than that in workers without RER (17.0 +/- 3.5 yr) (P = 0.0046). In addition, a longer period of chromate exposure was associated with a tendency toward a higher frequency of MSI. This finding suggests that MSI may play a role in chromium-induced carcinogenesis. In addition to our previous study of p53 mutations, the present findings suggest that the carcinogenic mechanism of chromate lung cancer may differ from that of non-chromate lung cancer.     

Deaths from non-melanoma skin cancer in Western Australia

Objectives  Non-melanoma skin cancer (NMSC) is common, slow growing, and rarely metastasizes. However, there are still nearly 400 deaths from NMSC in Australia annually. We aimed to investigate the accuracy of NMSC death coding and to describe the characteristics of these deaths and the potential for prevention. Methods  Histology reports for all deaths coded as NMSC (ICD-10 C44.0-C44.9) by the Western Australian Cancer Registry for the years 1996–2005 were reviewed for type of cancer, body site (primary tumor and metastases), and level of available documentation. Results  Of 368 deaths recorded as being due to NMSC only 3 were found to be miscoded. An additional 53 deaths contained inadequate information to confirm NMSC as the cause of death. Of the confirmed cases, 219 were due to squamous cell carcinoma, 53 to Merkel cell carcinomas, and 40 to other skin cancers. Cases were mainly males and were elderly. Most of the primary squamous and Merkel cell carcinomas were in areas of maximum sun exposure (face, ears, and hands, and scalp in males). Conclusions  Misclassification of NMSC deaths in WA was minimal. The majority of NMSC deaths were due to squamous cell carcinomas; had primary sites associated with significant sun exposure; and occurred in older men.     

Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy

Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild-type samples and a 17%-fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes.     

7例肺腺癌转化小细胞癌患者的临床病理特征分析

目的:分析总结肺腺癌转化为小细胞癌的临床病理特征。方法:回顾性分析2014年1月至2018年12月7例于河北医科大学第四医院确诊为肺腺癌转化为小细胞肺癌(small cell lung cancer,SCLC)患者的临床、病理及随访资料。结果:随访截至2020年6月1日。肺腺癌发生小细胞癌转化的中位时间为31个月,转化前应用酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)的中位时间为14个月。3例患者的转化部位与原发部位相同。7例患者转化前神经元特异性烯醇化酶(neuron-specific enolase,NSE)水平均升高,病情进展部位多为多个部位,肺、骨、脑、胸膜及淋巴结常见。7例患者转化后的免疫组织化学指标显示TTF1均为阳性,而Napsin A均为阴性,Syn、CD56、AE1/AE3均为阳性,Ki67均为高表达,PD-L1均不表达转化后基因检测显示,6例患者仍保持原有EGFR基因突变类型。转化后治疗主要为以化疗为主的综合治疗,中位无进展生存期为6个月,5例患者死亡,中位生存时间为10个月。结论:肺腺癌一旦发生小细胞癌转化,疾病进展迅速,生存期...     

非小细胞肺癌组织中CDKI(P27keap1)和CDK4的表达与患者生存期的相关性研究

目的检测非小细胞肺癌患者肿瘤组织中CDKI和CDK4的表达,回顾性分析其与患者生存期的相关性。方法选择行手术切除的83例非小细胞肺癌患者为研究对象,免疫组化检测P27^keap1和CDK4的表达,并于患者出院后均进行随访,记录每位患者生存期,分析非小细胞肺癌患者肿瘤组织中CDKI和CDK4的>表达与患者生存期的相关性。结果不同病理类型非小细胞肺癌患者癌组织CDKI(P27 keap1)和CDK4表达阳性率无显著差异(P>0.05),而不同分化程度、TMN分期以及淋巴结转移非小细胞肺癌患者癌组织CDK4表达阳性率均存在显著差异(P<0.05);与keap1阳性非小细胞癌患者相比,阴性患者生存期显著缩短(P<0.05),与CDK4阳性非小细胞癌患者相比,阴性患者生存期显著延长(P<0.05);相关性分析结果显示:keap1表达阳性率与非小细胞肺癌患者生存期呈显著负相关(γ<0,P<0.05),CDK4与非小细胞肺癌患者生存期呈显著正相关(γ>0,P<0.05)。结论非小细胞肺癌组织中CDKI(P27^keap1)和CDK4的表达与该肿瘤的的发生和进展密切相关,并进一步影响患者生存期。     

Adrenomedullin expression does not correlate with survival in lung cancer

It is suggested that adrenomedullin (AM) plays a role in lung carcinogenesis although, to confirm this suggestion, further clinical studies are needed to determine its relationship with prognosis in lung cancer. Archived 50 paraffin-embedded tumor samples of the lung were retrospectively evaluated for AM expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system. The pulmonary resection specimens contained 22 squamous cell carcinomas, 15 adenocarcinomas, and 13 small cell carcinomas. Non-small cell carcinomas of the lung were more likely to express AM than small cell carcinomas of the lung. Ninety-one percent of squamous cell carcinomas and 87% of adenocarcinomas expressed AM at a moderate to strong level and grade2–4 (30-100%), which were significantly higher from the non-neo-plastic lung tissue. Twenty-three percent of small cell carcinomas of lung expressed AM. Interestingly, AM immunoreactivity was essentially weak and grade 1 (<%30) in this group. AM expression is upregulated in non-small cell carcinomas of the lung, whereas it is downregulated in small cell carcinomas and non-neo-plastic lung tissues. AM expression did not show any correlation with the differentiation of the tumor, the stage of cancer, and the overall survival of patients. These results did not support the role of adrenomedullin as an independent survival factor for lung cancer. However, AM inhibition in conjunction with other anti-angiogenic agents may be useful in the prevention and treatment of malignancies.     

白细胞介素-18mRNA在非小细胞肺癌中的表达及其临床意义

目的:检测IL-18mRNA在非小细胞肺癌及癌组织中的表达,探讨其对非小细胞肺癌发生和发展过程的影响。方法:为非小细胞肺癌患者35例,男24例,女11例,年龄42-76岁,平均56岁,其中鳞癌17例(48.57%),腺癌13例(37.14%),腺鳞癌5例(14.29%)。对照组均来自距离肿瘤边缘2-4cm的正常肺组织。肿瘤直径≥4cm者6例(17.14%);肿瘤直径<4cm者29例(82.86%)。用RT-PCR法检测35例肺癌肿瘤组织细胞内和癌旁正常组织中的IL-18mRNA水平的表达。结果:在35例非小细胞肺癌中IL-18mRNA阳性表达率为100%,与癌旁正常组织比较,肺癌IL-18阳性表达率明显增高,差异有统计学意义(P<0.05)。结论:IL-18mRNA在NSCLC发展过程中发挥重要作用,其表达与患者年龄、性别和肿瘤组织类型无明显相关性,而与病理学分级、肿瘤T分期和有无淋巴结转移相关。     

Lung carcinoma with spindle and/or giant cell： a clinicopathological analysis of 17 cases

Objective: Lung carcinoma with spindle and (or) giant cell (LCSG) is a rare epithelial malignant tumor. The aim of our study is to investigate the clinicopathological and prognostic characteristics of 17 cases of LCSGs. Methods: Among 421 patients underwent resection of lung carcinomas, 17 cases of LCSG were studied for clinical, gross and histological parameters. Follow-up information was obtained and analyzed to clarify prognostically significant parameters. Results: The LCSG patients consisted of 15 males and 2 females, with the age ranging from 45 to 78 years (median, 58 years); 5 cases of stage Ⅰ, 3 of stage Ⅱ, 9 of stage Ⅲ by pathological TNM staging; 2 cases of exclusively spindle cell carcinoma, 5 cases of lung carcinoma with spindle cell, 10 cases of lung carcinoma with giant-cell carcinoma. Cough, chest distress, or chest pain were the most common presenting symptoms, occurring in 15 patients (88.2%). Of 5 patients in stage Ⅰ, 4 were alive and free of relapse for more than 5 years. The difference in survival was statistically significant between LCSG and squamous cell carcinoma patients (median survival, 36 vs. 61 months; P = 0.027). Lymph node metastasis and carcinoma with giant cell were the hazardous factors impacting postoperative prognosis of LCSG patients. Conclusion: LCSG patients in early stage may have an optimistic outcome. Lung carcinomas with giant cell displayed multiple cell components in histopathology, and poor outcome due to more lymph node involved.     

伊立替康联合顺铂治疗晚期非小细胞肺癌临床报告

目的评价伊立替康（CPT-11）联合顺铂（DDP）方案治疗晚期非小细胞肺癌（NSCLC）的疗效和不良反应。方法由国内4家医院协作研究完成。入组晚期NSCLC患者36例中,初次化疗24例,曾经化疗12例;全部患者均有可测量或可评价的指标。给药方法：CPT-1160mg／m^2静脉滴注,第1、8、15天;DDP80mg／m^2静脉滴注,第1天;28d为1个周期。结果36例患者共接受治疗97个周期,中位数为3个周期。可评价病例数为35例,无CR病例,PR8例（22．9％）,SD21例（60．0％）,PD6例（17．1％）。初治者有效率为29．2％（7／24）,复治者有效率为9．1％（1／11）,中位治疗至进展时间为199d,1年生存率为45．4％。Ⅲ、Ⅳ度不良反应发生率为粒细胞减少（16．7％）,脱发（13．9％）,腹泻（5．6％）,恶心呕吐（2．8％）。结论CPT-11联合DDP方案对晚期NSCLC治疗有效,患者耐受性良好,应进行深入研究。     

Folate receptor alpha expression in lung cancer: diagnostic and prognostic significance

With the advent of targeted therapies directed towards folate receptor alpha, with several such agents in late stage clinical development, the sensitive and robust detection of folate receptor alpha in tissues is of importance relative to patient selection and perhaps prognosis and prediction of response. The goal of the present study was to evaluate the expression of folate receptor alpha in non-small cell lung cancer specimens to determine its frequency of expression and its potential for prognosis. The distribution of folate receptor alpha expression in normal tissues as well as its expression and relationship to non-small cell lung cancer subtypes was assessed by immunohistochemistry using tissue microarrays and fine needle aspirates and an optimized manual staining method using the recently developed monoclonal antibody 26B3. The association between folate receptor alpha expression and clinical outcome was also evaluated on a tissue microarray created from formalin fixed paraffin embedded specimens from patients with surgically resected lung adenocarcinoma. Folate receptor alpha expression was shown to have a high discriminatory capacity for lung adenocarcinomas versus squamous cell carcinomas. While 74% of adenocarcinomas were positive for folate receptor alpha expression, our results found that only 13% of squamous cell carcinomas were FRA positive (p<0.0001). In patients with adenocarcinoma that underwent surgical resection, increased folate receptor alpha expression was associated with improved overall survival (Hazard Ratio 0.39, 95% CI 0.18-0.85). These data demonstrate the diagnostic relevance of folate receptor alpha expression in non-small cell lung cancer as determined by immunohistochemistry and suggest that determination of folate receptor alpha expression provides prognostic information in patients with lung adenocarcinoma.     

Gastrointestinal metastases from primary lung cancer

The aim of this study was to evaluate gastrointestinal metastases from primary lung cancer confirmed by autopsy. We identified and examined patients with a diagnosis of primary lung cancer over 33 years. We also reviewed patients with gastrointestinal metastases including the stomach, small bowel, and large bowel. This study comprised 470 patients with lung cancer. We detected 56 (11.9%) cases with gastrointestinal metastases. There were 12 (30%) cases with gastrointestinal metastases among 40 cases with large cell carcinoma. The histological type of large cell carcinoma led to a significantly higher rate of gastrointestinal metastases compared with that of non-large cell carcinoma (P = 0.004, odds ratio 3.524). Life threatening gastrointestinal metastases occurred in 12 cases and five occurred in large cell carcinoma. Gastrointestinal metastases from primary lung cancer may occur in the clinical course and result in life threatening gastrointestinal metastases, particularly if patients have the histological type of large cell carcinoma.     

白细胞介素-18mRNA在非小细胞肺癌中的表达及其临床意义

目的：检测IL-18mRNA在非小细胞肺癌及癌组织中的表达,探讨其对非小细胞肺癌发生和发展过程的影响。方法：为非小细胞肺癌患者35例,男24例,女11例,年龄42-76岁,平均56岁,其中鳞癌17例（48.57%）,腺癌13例（37.14%）,腺鳞癌5例（14.29%）。对照组均来自距离肿瘤边缘2-4cm的正常肺组织。肿瘤直径≥4cm者6例（17.14%）;肿瘤直径〈4cm者29例（82.86%）。用RT-PCR法检测35例肺癌肿瘤组织细胞内和癌旁正常组织中的IL-18mRNA水平的表达。结果：在35例非小细胞肺癌中IL-18mRNA阳性表达率为100%,与癌旁正常组织比较,肺癌IL-18阳性表达率明显增高,差异有统计学意义（P〈0.05）。结论：IL-18mRNA在NSCLC发展过程中发挥重要作用,其表达与患者年龄、性别和肿瘤组织类型无明显相关性,而与病理学分级、肿瘤T分期和有无淋巴结转移相关。     

Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma

Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss‐of‐heterozygosity (LOH), tumor ploidy and copy‐neutral allelic imbalance in lung cancer, microarray‐based genomic profiles from 2,141 tumors and cell lines including adenocarcinomas (AC, n = 1,206), squamous cell carcinomas (SqCC, n = 467), large cell carcinomas (n = 37) and small cell lung carcinomas (SCLC, n = 88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC array comparative genomic hybridization. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. Eighty‐nine recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. Thirteen and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n > 15) high‐level amplifications comprising established and putative oncogenes, differing in frequency and coamplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, LOH, copy‐neutral allelic imbalance and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease.     

Surgery versus stereotactic radiosurgery for single synchronous brain metastasis from non-small cell lung cancer

Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P<0.01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P>0.05).Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.     

间隙连接蛋白43和E-钙黏素在肺癌组织中的表达及临床意义

  目的 探讨间隙连接蛋白（Cx43）和上皮细胞钙黏素（E-钙黏素）在非小细胞肺癌中的表达特征及其临床意义。方法 应用免疫组化ABC法检测50例原发性肺癌组织中Cx43和E-钙黏素的表达情况，分析其表达与肺癌临床病理的关系。结果 Cx43和E-钙黏素在非小细胞肺癌中的阳性表达率分别为54 %和46 %，20例癌旁组织中均可见E-钙黏素和Cx43阳性表达。随着肿瘤进展，Cx43和E-cadherin表达逐渐降低，在Ⅰ、Ⅱ期非小细胞肺癌中阳性表达率明显高于Ⅲ、Ⅳ期；中、高分化的肺癌阳性表达率明显高于低分化的肺癌；肺癌伴淋巴结转移者的E-钙黏素表达水平低于无淋巴结转移者；Cx43表达与肺癌有无淋巴结转移无明显相关性。Cx43在肺腺癌组织中的阳性表达率明显高于鳞癌和大细胞未分化癌（P＜0.05）。E-钙黏素的表达与非小细胞肺癌的组织类型无明显相关性。     

肺鳞癌与人乳头瘤病毒相关性研究

目的:了解肺鳞癌组织中人乳头瘤病毒存在情况,并分析人乳头瘤病毒与肺癌发生部位、性别因素、角化程度、吸烟因素的关系.方法:采用地高辛标记的DNA探针对肺癌组织进行原位杂交检测,同时结合临床资料分析多种因素的相关性.结果:肺鳞癌组织,鳞状上皮生化组织、粘膜慢性炎组织HPV检出率分别为48.4%,27.4%,5.6%,各组比较差异显著(P＜0.01),中心型肺癌与周围型肺癌组织HPV检出率分别为50.6%和4.4%,两组比较差异显著(P＜0.01).男女两组HPV检出率分别为46.1%和54.3%,差异无显著性(P＞0.05).吸烟组HPV检出率为50.6%,非吸烟组为43.9%,差异不显著(P＞0.05).结论:肺癌组织中存在一定比例HPV感染,HPV感染与肺鳞癌关系密切,中心型肺癌与HPV感染密切相关,HPV感染与性别及吸烟因素未发现明显相关性.人乳头瘤病毒感染可能与肺癌发生发展有关.     

Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking

Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor that targets EGFR. We screened the EGFR in 469 resected tumours of patients with lung cancer, which included 322 adenocarcinomas, 102 squamous cell carcinomas, 27 large cell carcinomas, 13 small cell carcinomas, and five other cell types. PCR with a specific condition was performed to identify any deletion in exon 19, while mutant-allele-specific amplification was performed to identify a mutation in codon 858 of exon 21. EGFR mutations were found in 136 cases (42.2%) with adenocarcinoma, in one case with large cell carcinoma, and in one case with pleomorphic carcinoma. An in-frame deletion in exon 19 was found in 62 cases while an L858R mutation was found in 77 cases. In the 322 cases with adenocarcinoma, these mutations were more frequently found in women than in men (P=0.0004), in well differentiated tumours than in poorly differentiated tumours (P=0.0014), and in patients who were never smokers than in patients who were current/former smokers (P<0.0001). The mutation was more frequently observed in patients who smoked 相似文献   

肺癌胸水细胞块与组织学EGFR基因扩增检测对比研究

目的：对比肺癌胸水细胞块与组织学中EGFR基因扩增情况,探讨非小细胞肺癌患者阳性胸水细胞块检测EGFR基因扩增情况及临床意义。方法：收集60例非小细胞肺癌患者阳性胸水离心获取肿瘤细胞制作成石蜡细胞块,其中有28例的组织学对照,免疫组化分型后进行FISH检测EGFR基因,荧光显微镜观察基因扩增情况。结果：28例细胞块有组织学EGFR基因检测对照,在有组织学对照细胞块EGFR基因检测相符率100％。肺腺癌31例中,EGFR基因簇状扩增4例（12．9％）,点状扩增14例（45．2％）,无扩增13例（41．9％）,肺腺癌扩增率为58．1％;肺鳞癌25例中,EGFR基因簇状扩增2例（8．0％）,点状扩增9例（36．0％）,无扩增14例（56．0％）,肺鳞癌扩增率为44．0％;其他类型NSCLC患者4例中2例点状扩增,扩增率为50％。结论：肺腺癌及肺鳞癌胸水细胞块EGFR检测结果与组织学一致,EGFR基因在肺腺癌的扩增率高于肺鳞癌。应用FISH技术检测胸水细胞块中的EGFR基因扩增情况具有临床应用价值。