Uribe Pablo, Andrade Leonardo, Gonzalez Sergio
Department of Pathology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
J Invest Dermatol. 2006 Jan;126(1):161-6. doi: 10.1038/sj.jid.5700011.
The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase signaling pathway can be activated through mutations of V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) oncogene, frequently found in melanoma (60%), common nevi (CN) (73-82%), and atypical nevi (AN) (52-80%). MAPK activation has been reported between 0 and 22% in nevi, and 86% of primary melanoma, without any knowledge of BRAF mutational status. We studied the correlation of MAPK activation status, BRAF mutation, and B-Raf expression in CN, AN, and melanoma. Using immunohistochemistry, phosphorylated (active) MAPK and B-Raf expression was studied in 24 CN, 21 AN, and 26 primary cutaneous melanomas (PM). BRAF mutations at codon 600 were assessed by PCR-RFLP. Active MAPK was detected in 29% of CN, 48% of AN, and 85% of PM. BRAF mutation was found in 67% of CN, 62% of AN, and 58% of PM. In all, 23% of CN, 54% of AN, and 93% of PM with BRAF mutation have activated MAPK. All lesions expressed B-Raf. BRAF mutation does not seem to be sufficient to produce MAPK activation in melanocytic nevi, and it is suggested that other events are needed to induce MAPK activation, that is, B-Raf overexpression, inhibition of MAPK phosphatases, or suppression of RAF kinase inhibitors.
丝裂原活化蛋白激酶（MAPK）细胞外信号调节激酶信号通路可通过V-RAF鼠肉瘤病毒癌基因同源物B1（BRAF）癌基因突变激活，该突变在黑色素瘤（60%）、普通痣（CN）（73 - 82%）和非典型痣（AN）（52 - 80%）中经常出现。在不知道BRAF突变状态的情况下，已报道痣中MAPK激活率为0%至22%，原发性黑色素瘤中为86%。我们研究了CN、AN和黑色素瘤中MAPK激活状态、BRAF突变与B-Raf表达之间的相关性。采用免疫组织化学方法，研究了24例CN、21例AN和26例原发性皮肤黑色素瘤（PM）中磷酸化（活性）MAPK和B-Raf的表达。通过PCR-RFLP评估第600位密码子处的BRAF突变。在29%的CN、48%的AN和85%的PM中检测到活性MAPK。在67%的CN、62%的AN和58%的PM中发现BRAF突变。总体而言，BRAF突变的CN中有23%、AN中有54%、PM中有93%激活了MAPK。所有病变均表达B-Raf。BRAF突变似乎不足以在黑素细胞痣中产生MAPK激活，提示需要其他事件来诱导MAPK激活，即B-Raf过表达、MAPK磷酸酶抑制或RAF激酶抑制剂抑制。
