Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing
Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing
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DOI：
10.1158/1535-7163.mct-15-0615
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发表时间：
2015-12-01
影响因子：
5.7
通讯作者：
Broaddus, Russell R.
中科院分区：
文献类型：
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作者：
Estrella, Jeannelyn S.;Tetzlaff, Michael T.;Broaddus, Russell R.
虽然测序为鉴定BRAF V600E突变的结直肠癌提供了金标准，但最近开发的BRAF V600E蛋白小鼠单克隆抗体VE1的免疫组织化学（IHC）已显示出作为一种更广泛、更快速的方法的前景。然而，我们发现了VE1免疫组化与测序结果之间的不一致，因此通过两种不同的免疫组化方法（Leica Bond和Ventana BenchMark）分析了480例结直肠癌的全组织切片（323例BRAF野生型，142例BRAF V600E突变，15例BRAF非V600E突变）的VE1染色。我们还比较了黑色素瘤和甲状腺乳头状癌（PTC）的结果。Bond法在142例BRAF v600e突变的结直肠癌中，VE1弥漫染色77例（54%），异质染色48例（33%），阴性17例（12%）。323例BRAF野生型结直肠癌中，196例（61%）阴性，127例（39%）染色，其中7例为弥漫染色。当阳性定义为在>= 20%的肿瘤细胞中染色时，VE1 IHC对BRAF V600E突变的敏感性为75%，特异性为93%。使用Ventana方法，在57例BRAF v600e突变的结直肠癌中，36例（63%）有弥漫性VE1染色，而6例（11%）没有或微弱（< 20%的肿瘤细胞）染色。在33例BRAF野生型结直肠癌中，16例（48%）无染色或弱染色，而15例（45%）有异质染色。与结直肠癌相比，黑色素瘤和PTC中的Bond和Ventana VE1 IHC与测序结果高度一致。我们得出结论，VE1免疫组化治疗结直肠癌的效果不理想，不应用于指导患者管理。(c) 2015年aacr。
Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in >= 20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (< 20% of tumor cells) staining. Among 33 BRAF wildtype colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management. (C) 2015 AACR.