Gazdar A F
Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas.
Tohoku J Exp Med. 1992 Oct;168(2):239-45. doi: 10.1620/tjem.168.239.
Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. These changes include activation of dominant oncogenes myc family, (K-ras and neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and RB as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, such studies have not been performed to date. Documentation of molecular changes in premalignant lesions and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
肺癌是在一系列形态学变化之后发生的，从正常上皮细胞发展到浸润性癌需要数年时间。形态学变化从增生发展到化生，再到发育异常，到原位癌，再到浸润性癌，最终发展为转移性癌。在小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）中都记录了多种分子变化。变化的数量估计为两位数。这些变化包括显性癌基因myc家族（K-ras和neu基因）的激活，以及隐性生长调节基因或抑癌基因（p53、RB以及3号染色体上未确定的一个或多个基因）的缺失。然而，细胞遗传学和分子遗传学研究表明，肺癌中可能还存在多个其他实际或潜在的DNA缺失的特定位点。其他变化可能包括耐药性的产生以及生长因子及其受体的产生。人们很想将特定的分子变化与特定的形态学变化联系起来，就像在结肠癌研究中所尝试的那样。然而，由于对呼吸道进行连续采样存在困难，迄今为止尚未进行此类研究。记录癌前病变中的分子变化及其预后影响的前瞻性研究对于合理设计化学预防试验是必要的。
