Akslen Lars A, Angelini Sabrina, Straume Oddbjørn, Bachmann Ingeborg M, Molven Anders, Hemminki Kari, Kumar Rajiv
The Gade Institute, Section of Pathology, University of Bergen, Haukeland University Hospital, Bergen, Norway.
J Invest Dermatol. 2005 Aug;125(2):312-7. doi: 10.1111/j.0022-202X.2005.23788.x.
Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.
以往研究表明，皮肤黑色素瘤中BRAF（V-raf鼠肉瘤病毒癌基因同源物B1）或NRAS（神经母细胞瘤RAS病毒[v-ras]癌基因同源物）基因频繁发生突变，但在人类黑色素瘤中，这些改变与肿瘤细胞增殖之间的关系尚未得到研究。在我们对51例原发性结节性黑色素瘤和18对配对转移灶的研究中，我们发现15例原发性肿瘤（29%）和8例转移灶（44%）中存在BRAF（密码子600，先前称为599）突变。NRAS突变的比例分别为27%和22%。除1例病例外，BRAF和NRAS基因的突变相互排斥，且从原发性肿瘤到其转移灶均保持不变。然而，突变与通过Ki-67表达、肿瘤厚度、微血管密度或血管侵犯所反映的肿瘤细胞增殖无关，患者生存率也无差异。虽然BRAF和NRAS突变可能对某些黑色素瘤的发生和维持很重要，但对于侵袭性黑色素瘤亚组的增殖和预后，其他因素可能更为重要。
