Pulmonary preinvasive neoplasia
Pulmonary preinvasive neoplasia
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DOI：
10.1136/jcp.54.4.257
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发表时间：
2001-04-01
影响因子：
3.4
通讯作者：
Kerr, KM
中科院分区：
文献类型：
--
作者：
Kerr, KM
分子生物学的进展增加了我们对人肺肿瘤前病变生物学的认识。最近公布的WHO肺肿瘤分类定义了三种被认为是浸润前肿瘤的单独病变。这些是（1）鳞状不典型增生和原位癌（SD/CIS），（2）非典型腺瘤样增生（AAH）和（3）弥漫性特发性肺神经内分泌细胞增生（DIPNECH）。根据非典型细胞和有丝分裂像的分布，SD/CIS分为四个阶段（轻度、中度、重度和CIS）。大多数显示SD/CIS的气道表现出一系列等级;许多上皮细胞难以评估，并且该复杂系统的再现性仍有待建立。然而，详细的标准是受欢迎的，并提供了一个客观的框架，比较各种分子变化。已知与恶性转化相关的基因表达和染色体结构的改变可以在CIS中得到证实，在发育不良中较少，但也在形态正常的上皮中。这些变化可能是连续的，其频率和数量随着温度的升高而增加。目前对SD/CIS进展为浸润性“中央型”支气管癌的“风险”知之甚少。发生侵袭可能需要1至10年时间，但如果停止接触致癌物，病变可能是可逆的。AAH可能是肺外周“实质”腺癌的重要前驱病变：腺瘤-癌序列中的“腺瘤”。有很好的形态学证据表明，AAH可以从低级别发展到高级别，最后发展为细支气管肺泡癌（BAC;根据定义，这是一种非侵入性病变）。然后在BAC内发生侵袭，并发展为外周肺腺癌。与这种进展相关的分子事件尚未得到很好的理解，并且由于缺乏区分高级别AAH和BAG的明确标准，研究受到阻碍。尽管如此，与SD/CIS一样，肿瘤相关基因的表达模式与肿瘤进展一致。我们对正常或“吸烟”人群中AAH的发病率知之甚少。它更常见于肺癌，特别是腺癌，在女性中更常见。没有关于AAH进展风险的数据。DIPNECH是一种非常罕见的病变，与多发性类癌肿瘤的发展有关。对这些病变的了解对于设计和理解肺癌筛查方案至关重要，这些病变的形态学特征，更重要的是，这些病变的分子特征可能会为检测甚至治疗提供有用的靶点。
Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases.AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAG. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology.Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment.