Thiel Alexandra, Moza Monica, Kytölä Soili, Orpana Arto, Jahkola Tiina, Hernberg Micaela, Virolainen Susanna, Ristimäki Ari
Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital, 00029 Helsinki, Finland; University of Helsinki, 00014 Helsinki, Finland; Genome-Scale Biology, Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland.
Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital, 00029 Helsinki, Finland; University of Helsinki, 00014 Helsinki, Finland.
Hum Pathol. 2015 Feb;46(2):169-75. doi: 10.1016/j.humpath.2014.08.018. Epub 2014 Oct 30.
The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation is the most common activating genetic alteration of this oncogene and a predictive marker for the therapeutic use of BRAF inhibitors in melanoma. Our aim was to evaluate the performance of BRAF V600E mutation-specific monoclonal antibody (VE1) in a prospective diagnostic setting of melanoma patients (n = 102). All 41 cases (40.2%) that showed a V600E mutation in the cyclic minisequencing analysis of the DNA were also initially scored immunopositive. Two cases that were scored as BRAF V600E mutation positive by immunohistochemistry were negative in the DNA-based mutation analysis and determined to be immunonegative in a repeated staining with more representative specimens. Thus, BRAF V600E mutation detection using immunohistochemistry was 100% sensitive and 96.8% specific, when compared with the analysis of the DNA. None of the BRAF V600K mutations was detected by the VE1 antibody (n = 7). However, the VE1 antibody detected a rare V600E2 mutation. We also studied the role of BRAF V600E mutation in a set of melanoma patients who had been investigated for sentinel node metastasis. Melanoma lymph node metastases were diagnosed in 21.8% (12/55) of the sentinel nodes, and BRAF V600E immunopositivity was detected in 34.5% (19/55) of the cases. BRAF V600E mutation status did not correlate with any clinicopathological parameters. In conclusion, analysis of BRAF V600E mutation in melanoma by immunohistochemistry is a sensitive and specific method, which can be used to identify BRAF inhibitor-sensitive melanoma patients as a first-line method due to its rapid and affordable nature.
v-raf鼠肉瘤病毒癌基因同源物B1（BRAF）V600E突变是该癌基因最常见的激活基因改变，也是黑色素瘤中BRAF抑制剂治疗用途的预测标志物。我们的目的是在黑色素瘤患者（n = 102）的前瞻性诊断环境中评估BRAF V600E突变特异性单克隆抗体（VE1）的性能。在DNA的循环微测序分析中显示V600E突变的所有41例病例（40.2%）最初也被判定为免疫阳性。通过免疫组织化学判定为BRAF V600E突变阳性的2例病例在基于DNA的突变分析中为阴性，并在使用更具代表性的标本进行重复染色时被判定为免疫阴性。因此，与DNA分析相比，使用免疫组织化学检测BRAF V600E突变的敏感性为100%，特异性为96.8%。VE1抗体未检测到任何BRAF V600K突变（n = 7）。然而，VE1抗体检测到一种罕见的V600E2突变。我们还研究了BRAF V600E突变在一组已接受前哨淋巴结转移检查的黑色素瘤患者中的作用。在前哨淋巴结中，21.8%（12/55）被诊断为黑色素瘤淋巴结转移，34.5%（19/55）的病例检测到BRAF V600E免疫阳性。BRAF V600E突变状态与任何临床病理参数均无相关性。总之，通过免疫组织化学分析黑色素瘤中的BRAF V600E突变是一种敏感且特异的方法，由于其快速且经济的特性，可作为一线方法用于识别对BRAF抑制剂敏感的黑色素瘤患者。
