Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical School, Dallas, TX, USA.
Cancer Biomark. 2010;9(1-6):385-96. doi: 10.3233/CBM-2011-0166.
As with other epithelial cancers, lung cancer develops over a period of several years or decades via a series of progressive morphological changes accompanied by molecular alterations that commence in histologically normal epithelium. However the development of lung cancer presents certain unique features that complicates this evaluation. Anatomically the respiratory tree may be divided into central and peripheral compartments having different gross and histological anatomies as well as different functions. In addition, there are three major forms of lung cancer and many minor forms. Many of these forms arise predominantly in either the central or peripheral compartments. Squamous cell and small cell carcinomas predominantly arise in the central compartment, while adenocarcinomas predominantly arise peripherally. Large cell carcinomas are not a single entity but consist of poorly differentiated forms of the other types and, possibly, some truly undifferentiated "stem cell like" tumors. The multistage origin of squamous cell carcinomas, because of their central location, can be followed more closely than the peripherally arising adenocarcinomas. Squamous cell carcinomas arise after a series of reactive, metaplastic, premalignant and preinvasive changes. However, long term observations indicate that not all tumors follow a defined histologic course, and the clinical course, especially of early lesions, is difficult to predict. Peripheral adenocarcinomas are believed to arise from precursor lesions known as atypical adenomatous hyperplasias and may have extensive in situ growth before becoming invasive. Small cell carcinomas are believed to arise from severely molecularly damaged epithelium without going through recognizable preneoplastic changes. The molecular changes that occur prior to the onset on invasive cancers are extensive. As documented in this chapter, they encompass all of the six classic Hallmarks of Cancer other than invasion and metastasis, which by definition occur beyond preneoplasia. A study of preinvasive lung cancer has yielded much valuable biologic information that impacts on clinical management.
与其他上皮性癌症一样，肺癌经过数年或数十年的时间，通过一系列伴有分子改变的进行性形态学变化而发展，这些改变始于组织学正常的上皮。然而，肺癌的发展具有某些独特的特征，这使得评估变得复杂。解剖学上，呼吸树可分为中央和周围部分，具有不同的大体和组织解剖结构以及不同的功能。此外，有三种主要类型的肺癌和许多次要类型。这些类型中的许多主要发生在中央或周围部分。鳞状细胞癌和小细胞癌主要发生在中央部分，而腺癌主要发生在周围。大细胞癌不是一个单一的实体，而是由其他类型的低分化形式组成，可能还有一些真正未分化的“干细胞样”肿瘤。由于其位于中央，鳞状细胞癌的多阶段起源可以比外周起源的腺癌更密切地跟踪。鳞状细胞癌发生在一系列反应性、化生、癌前和癌前病变之后。然而，长期观察表明，并非所有肿瘤都遵循明确的组织学过程，尤其是早期病变的临床过程难以预测。周围性腺癌被认为起源于称为非典型腺瘤性增生的前体病变，并且在侵袭之前可能具有广泛的原位生长。小细胞癌被认为起源于严重分子受损的上皮，而没有经历可识别的癌前病变变化。在侵袭性癌症发生之前发生的分子变化是广泛的。正如本章所记录的，它们涵盖了癌症的六个经典标志中的除侵袭和转移之外的所有标志，根据定义，侵袭和转移发生在癌前病变之外。对肺癌的癌前病变的研究产生了许多有价值的生物学信息，这些信息影响临床管理。
