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胸腔灌洗的细胞学检查并结合p16和O6-甲基鸟嘌呤-DNA甲基转移酶基因启动子高甲基化研究在非小细胞肺癌胸膜转移变化诊断中的应用

Cytological examination of pleural cavity lavage accompanied by the study of gene promoter hypermethylation of p16 and O6-methylguanine-DNA-methyltransferase genes in diagnostics of non-small cell lung cancer metastatic changes into pleura.

作者信息

Kaczmarczyk Grzegorz, Lewandowski Roman, Trautsolt Wanda, Ziółkowski Adam, Kozielski Jerzy

机构信息

Department and Clinic of Lung Diseases and Tuberculosis in Zabrze, Silesian Medical University in Katowice, Poland.

出版信息

Contemp Oncol (Pozn). 2012;16(4):322-7. doi: 10.5114/wo.2012.30061. Epub 2012 Sep 29.

Abstract

AIM OF THE STUDY

Metastases of non-small cell lung cancer (NSCLC) into pleura disqualify a patient from surgery and present a bad prognostic index. The aim of the study was to find out whether washing out the pleural cavity in such cases and examining obtained washings for presence of cancer cells will help to detect early NSCLC metastases into pleura, and also whether negative results of the cytology determine whether hypermethylation of these genes will increase the sensitivity of this examination.

MATERIAL AND METHODS

The study consisted of the examination of 76 patients, including 59 operated on for NSCLC and 17 operated on for other reasons. Pleural washing fluid collected during the surgery was subjected to cytological examination as well as examined to determine the presence of promoter region hypermethylation of p16 and MGMT genes.

RESULTS

Positive cytological results of pleural lavage were confirmed in 4 persons (7%) with NSCLC. The presence of promoter region hypermethylation of one or both examined genes was found in 3 patients (18%) in the control group and in 47 (80%) in the study group. Sex, occupational exposure, smoking cigarettes, and NSCLC histological type did not have an influence on the presence of cancer cells or hypermethylation in the pleural lavage fluid. Positive cytology results were more frequent at the T4 stage of NSCLC. Hypermethylation was more frequent in the research group (p < 0.01). Cancer cells and hypermethylation did not occur more frequently in pleural lavage fluid of patients with metastases into pleura.

CONCLUSIONS

The cytological examination and promoter region hypermethylation assessment of the p16 gene and MGMT gene in pleural lavage cells do not allow one to detect early metastasis of NSCLC into pleura.

摘要

研究目的

非小细胞肺癌(NSCLC)转移至胸膜会使患者失去手术资格,并提示预后不良。本研究的目的是探究在此类病例中冲洗胸腔并检查所得冲洗液中是否存在癌细胞,是否有助于检测NSCLC早期胸膜转移,以及细胞学检查结果为阴性时,这些基因的高甲基化是否会提高该检查的敏感性。

材料与方法

本研究包括对76例患者的检查,其中59例因NSCLC接受手术,17例因其他原因接受手术。手术期间收集的胸腔冲洗液进行了细胞学检查,并检测了p16和MGMT基因启动子区域高甲基化情况。

结果

NSCLC患者中有4人(7%)胸膜灌洗细胞学检查结果为阳性。对照组3例患者(18%)以及研究组47例患者(80%)检测到一个或两个检测基因启动子区域高甲基化。性别、职业暴露、吸烟及NSCLC组织学类型对胸腔冲洗液中癌细胞的存在或高甲基化无影响。NSCLC T4期时,细胞学检查阳性结果更为常见。研究组高甲基化更为常见(p<0.01)。胸膜转移患者胸腔冲洗液中癌细胞和高甲基化的出现频率并未更高。

结论

对胸腔冲洗细胞进行细胞学检查以及p16基因和MGMT基因启动子区域高甲基化评估,无法检测出NSCLC早期胸膜转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ad0/3687432/76cc99ffc009/WO-16-19109-g001.jpg

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