Flinders University and SA Pathology, Adelaide, South Australia, Australia.
Pathology. 2013 Apr;45(3):305-15. doi: 10.1097/PAT.0b013e32835f45fd.
Lung cancer is now the leading cause of death from cancer in Australia. Most patients are diagnosed with late-stage disease. Although diagnosis at pre-invasive stages could theoretically improve outcomes, mooted precursor lesions are often asymptomatic and often undetectable by non-invasive investigations. Nonetheless, they merit study to identify early and essential molecular steps involved in lung carcinoma pathogenesis, with the aim of developing therapies targeted against one or more such steps. Some lung cancers appear to develop via a series of progressive morphological changes with correlating molecular alterations, but others seem to arise in histologically normal epithelium, and these differences may reflect anatomically and functionally distinct epithelial compartments of the respiratory tract. Pre-invasive precursor lesions recognised by the World Health Organization (WHO) include squamous metaplasia with dysplasia and carcinoma in situ, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Other lesions that likely represent pre-invasive lesions, but which are not currently WHO-listed, include human papillomavirus (HPV)-related respiratory papillomatosis and mesothelioma in situ. No single cancer stem cell marker has been identified. Field cancerisation plays an important role in lung cancer development, and includes the spread of pre-invasive clones along the respiratory epithelium or the occurrence of multiple separate foci of pre-invasive abnormalities such as squamous dysplasia and carcinoma in situ.In addition to well-characterised step-wise progression in squamous cell carcinomas and some adenocarcinomas, alternative pathways exist, and are currently being investigated. In addition, molecular techniques, including miRNA screening on blood samples or cytology samples--such as sputum samples--may become clinically relevant and more accurate in predicting lung cancer progression.
肺癌是澳大利亚癌症死亡的主要原因。大多数患者被诊断为晚期疾病。尽管在侵袭前阶段诊断可以理论上改善结果，但推测的前驱病变通常是无症状的，并且通常无法通过非侵入性研究检测到。尽管如此，它们值得研究，以确定涉及肺癌发病机制的早期和基本分子步骤，目的是开发针对一个或多个此类步骤的治疗方法。一些肺癌似乎通过一系列具有相关性的分子改变的进行性形态变化发展，但另一些似乎起源于组织学正常的上皮细胞，这些差异可能反映了呼吸道的解剖学和功能上不同的上皮隔室。世界卫生组织（WHO）认可的侵袭前前驱病变包括鳞状化生伴异型增生和原位癌、非典型性腺瘤样增生和弥漫性特发性肺神经内分泌细胞增生。其他可能代表侵袭前病变但目前未被 WHO 列出的病变包括与人类乳头瘤病毒（HPV）相关的呼吸道乳头瘤病和间皮原位癌。尚未确定单一的癌症干细胞标志物。肿瘤发生在肺癌的发展中起着重要作用，包括侵袭前克隆沿着呼吸道上皮的扩散，或多个侵袭前异常灶如鳞状异型增生和原位癌的发生。除了在鳞状细胞癌和一些腺癌中已经很好地描述了逐步进展外，还存在其他途径，目前正在研究中。此外，分子技术，包括血液样本或细胞学样本（如痰样本）上的 miRNA 筛选，可能在临床上变得相关，并且更准确地预测肺癌的进展。
