Hiroshima K, Toyozaki T, Kohno H, Ohwada H, Fujisawa T
Division of Pathology, Institute of Pulmonary Cancer Research, Chiba University School of Medicine, Japan.
Pathol Int. 1998 Nov;48(11):869-76. doi: 10.1111/j.1440-1827.1998.tb03853.x.
The present study is aimed to evaluate the genetic evidence for multicentricity of synchronous and metachronous multiple lung carcinomas. Nineteen cases of synchronous multiple lung carcinomas and 11 cases of metachronous multiple lung carcinomas were analyzed for p53 protein overexpression by immunohistochemistry (DO-7) and for genetic abnormality of the p53 gene by loss of heterozygosity (LOH) at chromosome 17p and by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. They were also analyzed for K-ras mutation. DNA from three patients was also sequenced by the dideoxy sequencing method to confirm the presence of mutations and determine the base substitutions. Different spectrums of genetic changes, which were evaluated by a combination of p53 mutation, LOH at chromosome 17p and p53 overexpression, were observed in 11 of 19 cases of synchronous multiple lung carcinomas (57.9%) in the present study. Similarly, five of 11 cases of metachronous multiple lung carcinomas (45.4%) showed a different pattern of genetic changes. The present data suggest that some of the multiple carcinomas have different clonal origins, although their histological types are identical, and support the use of genetic markers in the differential diagnosis between metastasis and second primary carcinoma of the lung.
本研究旨在评估同步性和异时性多发性肺癌多中心性的遗传学证据。通过免疫组织化学（DO-7）分析19例同步性多发性肺癌和11例异时性多发性肺癌的p53蛋白过表达情况，并通过17号染色体短臂杂合性缺失（LOH）及聚合酶链反应（PCR）-单链构象多态性（SSCP）分析检测p53基因的遗传异常。同时对其进行K-ras突变分析。对3例患者的DNA也采用双脱氧测序法进行测序，以确认突变的存在并确定碱基置换情况。在本研究中，19例同步性多发性肺癌中的11例（57.9%）观察到不同的遗传改变谱，这些改变通过p53突变、17号染色体短臂LOH及p53过表达的联合分析进行评估。同样，11例异时性多发性肺癌中的5例（45.4%）表现出不同的遗传改变模式。目前的数据表明，部分多发性癌尽管组织学类型相同，但具有不同的克隆起源，并支持在肺转移癌和第二原发性肺癌的鉴别诊断中使用遗传标志物。
