A STUDY OF TUMOR PROGRESSION - THE PRECURSOR LESIONS OF SUPERFICIAL SPREADING AND NODULAR MELANOMA
A STUDY OF TUMOR PROGRESSION - THE PRECURSOR LESIONS OF SUPERFICIAL SPREADING AND NODULAR MELANOMA
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DOI：
10.1016/s0046-8177(84)80310-x
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发表时间：
1984-01-01
期刊：
影响因子：
3.3
通讯作者：
VANHORN, M
中科院分区：
文献类型：
--
作者：
CLARK, WH;ELDER, DE;VANHORN, M
肿瘤进展的六个明显的病变步骤形成了影响人表皮黑素细胞的肿瘤系统：常见的获得性黑素细胞痣;黑素细胞痣伴雀斑样黑素细胞增生，即，异常分化;具有异常分化和黑素细胞核色素沉着的黑素细胞痣，即，黑素细胞发育不良;原发性黑素瘤的径向生长期;原发性黑素瘤的垂直生长期;和转移性黑素瘤。常见的获得性黑素细胞痣被认为是黑素细胞的局灶性增殖，在大多数情况下注定要遵循程序化的分化途径，导致痣的消失。如果没有遵循分化途径，就会产生特征性病变，这种病变被认为是黑色素瘤的正式组织发生前体。这种发育缺陷被称为异常分化，由此产生的前驱病变被称为黑素细胞发育不良。绝大多数显示黑素细胞发育不良的黑素细胞痣是不进展为黑色素瘤的终末病变。如果黑色素瘤是通过前驱病变发展的，那么伴有黑素细胞发育不良的痣就是前驱病变。当黑色素瘤发展时，它们在前体中局部发展。由此产生的原发性黑色素瘤本身并不遵循黑色素瘤细胞群体在空间和时间上不可阻挡地扩张的途径。原发性黑色素瘤，除了结节性黑色素瘤，也是逐步发展的。第一步，称为放射状生长期，其特征是肿瘤在其周边沿着不完美圆的半径的净增大。在这个发展阶段的肿瘤显示出在表皮内生长的特征性模式和乳头状真皮的独特形式的侵袭。这样的黑色素瘤与转移无关，并且假设这样的肿瘤不具有转移能力。黑色素瘤要获得转移的能力，它必须进展到肿瘤进展的下一步，即垂直生长期。该损伤步骤的特征在于黑色素瘤内新细胞群的出现，而不是形成预先存在的放射状生长期的细胞的扩增。垂直生长期细胞的净生长垂直于径向生长期的定向生长。通常，垂直生长期的细胞以膨胀的方式生长，随着球囊膨胀而膨胀：转移瘤的特征性生长形式。垂直生长期的细胞是引起转移的细胞;肿瘤进展的最后一个病变步骤是转移。本文中描述的肿瘤进展的病变被认为是肿瘤形成的范例，并且从该模型中提出了一般适用于肿瘤发展的一般病变序列。肿瘤进展的这些一般步骤是：结构正常细胞的选择性局灶性增殖（良性肿瘤）;异常模式的增生（异常分化）;异常模式的增生和随机细胞学异常（异常分化和出现具有核细胞的细胞）;原发性癌症无转移能力;原发性癌症有转移能力;和转移性癌症。
Six evident lesional steps of tumor progression form the neoplastic system that affects the human epidermal melanocyte: the common acquired melanocytic nevus; a melanocytic nevus with lentiginous melanocytic hyperplasia, i.e., aberrant differentiation; a melanocytic nevus with aberrant differentiation and melanocytic nuclear atypia, i.e., melanocytic dysplasia; the radial growth phase of primary melanoma; the vertical growth phase of primary melanoma; and metastatic melanoma. The common acquired melanocytic nevus is viewed as a focal proliferation of melanocytes, destined in most instances to follow a programmed pathway of differentiation that leads to disappearance of the nevus. If the pathway of differentiation is not followed, characteristic lesions result, and such lesions are regarded as the formal histogenic precursors of melanoma. Such a developmental flaw is termed aberrant differentiation, and the resultant precursor lesion is designated melanocytic dysplasia. The vast majority of melanocytic nevi showing melanocytic dysplasia are terminal lesions that do not progress to melanoma. If melanoma is to develop via a precursor lesion, the nevus with melanocytic dysplasia is that precursor. When melanomas do develop, they develop focally within the precursor. The resultant primary melanoma itself does not follow a pathway of inexorable expansion of a population of melanoma cells in space and time. Primary melanomas, with the exception of nodular melanoma, also evolve in a stepwise fashion. The first step, termed the radial growth phase, is characterized by the net enlargement of the tumor at its periphery, along the radii of an imperfect circle. Tumors in this stage of development show a characteristic pattern of growth within the epidermis and a distinctive form of invasion of the papillary dermis. Such melanomas are not associated with metastasis, and it is hypothesized that such tumors do not have competence for metastasis. For a melanoma to acquire competence for metastasis it must progress to the next step of tumor progression.sbd.the vertical growth phase. This lesional step is characterized by the apperance of a new population of cells within the melanoma, not an expansion of the cells forming the preexisting radial growth phase. The net growth of the cells of the vertical growth phase is perpendicular to the directional growth of the radial growth phase. As a rule, the cells of the vertical growth phase grow in an expansile fashion, expansile as a balloon expands: a growth form characteristic of metastases. The cells of the vertical growth phase are those that give rise to metastasis; the last lesional step of tumor progression is metastasis. The lesions of tumor progression described in this paper are thought to be a paradigm for neoplasia, and from this model a sequence of generic lesions applicable to neoplastic development in general is presented. These generic steps of tumor progression are: a selective focal proliferation of structurally normal cells (a benign tumor); an abormal pattern of hyperplasia (aberrant differentiation); an abnormal pattern of hyperplasia and random cytologic atypia (aberrant differentiation and the appearance of cells with nucelar atypia); primary cancer without competence for metastases; primary cancer with competence for metastasis; and metastatic cancer.