Pelosi Giuseppe, Scarpa Aldo, Manzotti Michela, Veronesi Giulia, Spaggiari Lorenzo, Fraggetta Filippo, Nappi Oscar, Benini Elvira, Pasini Felice, Antonello Davide, Iannucci Antonio, Maisonneuve Patrick, Viale Giuseppe
Department of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy.
Mod Pathol. 2004 May;17(5):538-46. doi: 10.1038/modpathol.3800058.
We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.
我们采用聚合酶链反应-单链构象多态性分析及直接测序法，对27例肺多形性癌的第1外显子K-ras基因突变情况进行了研究。所有多形性癌均为双相性，即由腺、鳞或大细胞癌成分与梭形和/或巨细胞成分组成。27例病例中，6例（22%）出现K-ras密码子12突变，这一数字高于先前报道的纯肉瘤样多形性癌。5例肿瘤的上皮成分和肉瘤样成分均显示相同突变，而1例肿瘤的突变仅局限于上皮成分。所有突变均发生在吸烟者中，且均为颠换，包括2例由GGT（甘氨酸）突变为TGT（半胱氨酸），2例突变为GCT（丙氨酸），2例突变为GTT（缬氨酸）。未发现突变的发生及类型与患者生存或任何其他临床病理变量之间存在显著相关性，提示K-ras突变是这些肿瘤发生发展过程中的早期事件。我们的结果表明，大多数（尽管不是全部）肺双相性多形性癌起源于单克隆，且吸烟可能在这些肿瘤的K-ras改变发生过程中起致病作用，因为所有突变均为颠换。
