肺多原发癌或转移癌鉴别诊断研究进展

Differential diagnosis of multiple tumor:multiple primary cancer or metastatic cancer of lung

目的:总结肺多原发癌及转移癌发生的分子机制,以及临床鉴别诊断的新进展。方法:以"肺多原发癌、肺转移和诊断"等为关键词,检索2008-01-2012-12PubMed及CNKI期刊全文数据库。纳入标准:1)肺多原发癌及转移癌的分子机制;2)肺多原发癌及转移癌的外科治疗;3)分子及基因分析在肺多原发癌诊断中的价值。根据纳入标准,符合分析的文献26篇。结果:肺多原发癌发病率逐年上升,目前对肺多原发癌与转移癌的准确诊断仍较困难。复习文献发现,"区域癌变学说"被证实存在于肺组织中,致癌因子在不同位置的肺组织导致相异的基因突变,如微卫星杂合性缺失和p53基因突变等,最终形成具有异质性基因表型的多原发癌;相反的,转移癌与原发灶之间存在着相同或相似的组织学起源和基因表达谱,研究发现其微卫星杂合性缺失及p53基因突变相似。综上所述,肺多原发癌与转移癌之间起源的差异为分子或基因变化,可为多原发癌与转移癌的鉴别诊断提供理论依据。结论:基于肺多原发癌与转移癌形成的分子机制差异,发现可用于诊断的分子标志(如微卫星杂合性缺失和p53基因突变等),有助于肺多原发癌与转移癌鉴别诊断及改善患者的预后。

OBJECTIVE：To review current advances of the molecular mechanism and clinic diagnosis in multiple primary lung cancers and metastatic cancers. METHODS： Articles published between Jan. 2008 and Dec. 2012 had been retrieved with keywords of multiple primary lung cancer,intrapulmonary metastasis and diagnosis in PubMed and CNKI. In- clusive criteria：l） the molecular mechanism in multiple primary lung cancers or metastatic cancers;2） surgical therapy in multiple primary lung cancers or metastatic cancers; 3） the value of molecular and genetic analysis in diagnosis of multiple primary lung cancer. Totally 26 articles were in accordance with the inclusive criteria. RESULTS： The incidence rate of multiple primary lung cancer is increased,however the critically diagnosis of the multiple primary lung cancer and meta- static cancer remains a formidable challenge. After fully reviewed references, we discovered that the ＂field cancerization hypothesis＂ has been verified existed in lung tissues, carcinogens result in different gene mutations in different positions of lung tissues,and form multiple primary lung cancer with a heterogeneous genotype including loss of heterozoygosity, p53 gene mutation etc. On the contrary, there have the same or parallel histological type and gene expression profile（for exam- ple loss of heterozoygosity,p53 gene mutation） between primary tumor and metastatic tumor in metastatic cancer. From the studies mentioned above, based on the initial difference of multiple primary cancer and metastatic cancer, the molecular or genetic alternation may provide theoretical basis for differential diagnosis between multiple primary lung cancers and metastatic cancers. CONCLUSION： Based on the molecular mechanism difference of the formation of multiple primary lung cancers and metastatic cancers,find some biomarkers such as LOH and p53 somatic mutations, contribute to the proper differential diagnosis of multiple primary lung cancers and metastatic cancers, and improve the prognosis.