Shen Steven S, Zhang Peter S, Eton Omar, Prieto Victor G
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, The University of Texas M.D. Houston, TX, USA.
J Cutan Pathol. 2003 Oct;30(9):539-47. doi: 10.1034/j.1600-0560.2003.00090.x.
It has been proposed that melanoma progression involves a multistep process from benign nevi (BN), dysplastic nevi (DN), radial and vertical growth phase melanoma (MM) to metastatic melanoma (MMM). Protein tyrosine kinases (PTKs) may participate in this progression.
Tissue microarray blocks of 89 melanocytic lesions were evaluated by immunohistochemistry for the expression of selected PTKs: c-kit, c-abl, abl-related gene (ARG), platelet-derived growth factor receptors alpha (PDGFR-alpha) and beta (PDGFR-beta).
Seventeen of 31 (55%) MMM lacked expression of c-kit versus 100% expression (18/18) in DN and 96% expression (22/23) in MM; similarly, only 59% (10/17) of BN showed expression of c-kit. PDGFR-beta expression levels were similar in BN, DN, and MM, but lower in MMM. There was a trend toward lower expression of abl and ARG from BN to MMM. There was a marked decrease in staining intensity of ARG from BN to DN, MM, and MMM.
Our results support that BN is different from DN and MM and that these two are different from MMM. Metastasis appears to be associated with loss of c-kit and PDGFR-beta expression. Since malignant melanoma expresses PTK, it may be a candidate for treatment with anti-PTK, such as STI-571 (Gleevec).
有人提出黑色素瘤的进展涉及一个多步骤过程，从良性痣（BN）、发育异常痣（DN）、径向和垂直生长期黑色素瘤（MM）到转移性黑色素瘤（MMM）。蛋白酪氨酸激酶（PTK）可能参与这一进展过程。
通过免疫组织化学评估89个黑素细胞病变的组织芯片块中所选PTK的表达情况：c-kit、c-abl、abl相关基因（ARG）、血小板衍生生长因子受体α（PDGFR-α）和β（PDGFR-β）。
31例MMM中有17例（55%）缺乏c-kit表达，而DN中c-kit表达率为100%（18/18），MM中为96%（22/23）；同样，只有59%（10/17）的BN显示c-kit表达。BN、DN和MM中PDGFR-β的表达水平相似，但MMM中较低。从BN到MMM，abl和ARG的表达有降低趋势。从BN到DN、MM和MMM，ARG的染色强度明显降低。
我们的结果支持BN与DN和MM不同，且这两者与MMM也不同。转移似乎与c-kit和PDGFR-β表达缺失有关。由于恶性黑色素瘤表达PTK，它可能是抗PTK治疗的候选对象，如STI-571（格列卫）。
