Göppner Daniela, Leverkus Martin
Department of Dermatology and Venereology, Otto-von-Guericke-University Hospital, Leipziger Str. 44, 39120 Magdeburg, Germany.
J Skin Cancer. 2011;2011:521947. doi: 10.1155/2011/521947. Epub 2011 Oct 11.
Due to intensified research in recent years, the understanding of the molecular mechanisms involved in the development of melanoma has dramatically improved. The discovery of specific, causal mutations such as BRAF or KIT oncogenes not only renders a targeted and thus more effective therapeutic approach possible, but also gives rise to a new genetic-based classification. Targeting just a few out of several potential mutations, BRAF-Inhibitors such as PLX 4032 achieved already tremendous results in the therapy of metastatic melanoma. Up to now, the correlation of clinical, histomorphologic, and genetic features is, however, not understood. Even more, is it not well known precisely what kind of molecular changes predispose the primary melanoma for metastasis. The identification of morphological surrogates and prognostic parameters in tumors with such genetic alteration seems therefore crucial when differentiating and classifying this heterogeneous tumor entity in more detail and thus facilitates the stratification of prognosis as well as therapy. This review summarizes the current understanding of carcinogenesis and gives a detailed overview of known morphologic and potentially future genetic prognostic parameters in malignant melanoma.
由于近年来研究的强化,对黑色素瘤发生发展所涉及分子机制的理解有了显著提高。BRAF或KIT癌基因等特定因果突变的发现,不仅使靶向治疗成为可能,进而提高治疗效果,还引发了基于基因的新分类方法。仅针对几种潜在突变中的少数几种,如PLX 4032这类BRAF抑制剂,在转移性黑色素瘤治疗中已取得了巨大成果。然而,目前临床、组织形态学和基因特征之间的相关性尚不清楚。更确切地说,对于何种分子变化使原发性黑色素瘤易于发生转移也并不明确。因此,在更详细地区分和分类这种异质性肿瘤实体时,识别具有此类基因改变的肿瘤中的形态学替代指标和预后参数,对于判断预后以及制定治疗方案似乎至关重要。本综述总结了目前对致癌作用的理解,并详细概述了恶性黑色素瘤中已知的形态学以及潜在的未来基因预后参数。