Chuang Jody C, Shrager Joseph B, Wakelee Heather A, Neal Joel W
Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, California.
Division of Thoracic Surgery, Stanford University School of Medicine, Stanford, California.
Clin Ther. 2016 Jul;38(7):1567-76. doi: 10.1016/j.clinthera.2016.06.005. Epub 2016 Jun 29.
Adenocarcinoma remains the most common subtype of lung cancer in the United States. Most patients present with tumors that are invasive and often metastatic, but in some patients, multiple precursor in situ or minimally invasive adenocarcinoma tumors develop that can be synchronous and metachronous. These precursor lesions harbor the same spectrum of genetic mutations found in purely invasive adenocarcinomas, such as EGFR, KRAS, and p53 mutations. It is less clear, however, whether separate lesions in patients who present with multifocal disease share common underlying genetic driver mutations.
Here we review the relevant literature on molecular driver alterations in adenocarcinoma precursor lesions. We then report 4 patients with multifocal EGFR mutant adenocarcinomas in whom we performed molecular testing on 2 separate lesions.
In 2 of these patients, the mutations are concordant, and in 2 patients, the mutations are discordant. A review of the literature demonstrates increasing evidence that lesions with discordant mutations may confer a more favorable prognosis because they are unlikely to represent metastases.
Our findings suggest that the emergence of the dominant EGFR driver alteration is often independent between lesions in patients with multifocal adenocarcinomas, and thus the same targeted therapy may not be effective for all lesions. However, genetic testing of multiple lesions can help to distinguish separate primary tumors from metastatic disease.
在美国，腺癌仍然是肺癌最常见的亚型。大多数患者表现为侵袭性且常为转移性的肿瘤，但在一些患者中，会出现多个原位或微侵袭性腺癌前体肿瘤，这些肿瘤可以是同时性的和异时性的。这些前体病变具有与纯侵袭性腺癌相同的一系列基因突变，如表皮生长因子受体（EGFR）、 Kirsten 大鼠肉瘤病毒癌基因（KRAS）和抑癌基因p53突变。然而，对于多灶性疾病患者中不同的病变是否共享共同的潜在基因驱动突变，目前尚不清楚。
在此，我们回顾了有关腺癌前体病变分子驱动改变的相关文献。然后报告了4例多灶性EGFR突变腺癌患者，我们对其2个不同的病变进行了分子检测。
在这些患者中，2例的突变是一致的，2例的突变是不一致的。文献综述表明，越来越多的证据表明，具有不一致突变的病变可能预示着更有利的预后，因为它们不太可能是转移灶。
我们的研究结果表明，在多灶性腺癌患者中，主要的EGFR驱动改变的出现通常在不同病变之间是独立的，因此相同的靶向治疗可能并非对所有病变都有效。然而，对多个病变进行基因检测有助于区分独立的原发性肿瘤和转移性疾病。
