BRAF(V)(600E) mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary.
BRAF(V)(600E) mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary.
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DOI：
10.1111/his.13651
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发表时间：
2018-09
期刊：
影响因子：
6.4
通讯作者：
Murali R
中科院分区：
文献类型：
--
作者：
Turashvili G;Grisham RN;Chiang S;DeLair DF;Park KJ;Soslow RA;Murali R
卵巢低级别浆液性肿瘤(LGSNs)中最常见的BRAF突变涉及第600位(V600E)由谷氨酸取代Valine。小规模研究表明，突变特异性单抗VE1免疫组织化学具有很高的特异性。我们试图研究VE1蛋白在LGSN中的表达及其与BRAF突变相关的组织学特征和BRAF突变状态的相关性。我们回顾了2000-2012年间诊断的卵巢浆液性交界性肿瘤(SBTS)和低级别浆液性癌(LGSCs)的病理报告和可用的切片。对福尔马林固定、石蜡包埋的组织切片进行VE1免疫组织化学染色。≥阳性细胞50%的肿瘤被认为是阳性。采用SPSS24.0统计软件进行统计分析。在121个LGSNs中，73个为SBTS，8个具有微乳头特征(MpSBT)，40个LGSCs(22个原发灶，18个转移灶)。VE1在52%(38/73)的SBTS和9%(2/22)的原发LGSCs中呈阳性表达，在mpSBT和转移性LGSCs中均为阴性(p<；0.0001)。在已知突变状态的76个肿瘤中，42个(55%)含有突变，包括BRAFV600E(26个，34%)、KrasG12D(8个，11%)和KRASG12V(8个，11%)。BRAFV600E突变见于48%(25/52)的SBTS和5%(1/22)的LGSC(p<；0.0001)。在BRAFV600E突变的肿瘤中，VE1的阳性率为96%(25/26)，并且与BRAF突变相关的组织学特征相关(p<；0.0001)。BRAFV600E突变在SBTS中比在LGSC中更常见。VE1蛋白的免疫组织化学表达与BRAFV600E突变和BRAF突变相关的组织学特征密切相关。VE1免疫组织化学是检测BRAFV600E突变的可靠方法。
The most common BRAF mutation in ovarian low-grade serous neoplasms (LGSNs) involves substitution of valine by glutamic acid at position 600 (V600E). Small studies have demonstrated high specificity of immunohistochemistry with mutation-specific monoclonal antibody VE1. We sought to investigate expression of VE1 protein in LGSNs and its correlation with BRAF mutation-associated histological features and BRAF mutation status. We reviewed pathology reports and available slides from ovarian serous borderline tumours (SBTs) and low-grade serous carcinomas (LGSCs) diagnosed between 2000-2012. VE1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections. Tumours with ≥50% positive cells were considered positive. Statistical analyses were performed using SPSS 24.0. Of 121 LGSNs, there were 73 SBTs, 8 SBTs with micropapillary features (mpSBT), and 40 LGSCs (22 primary, 18 metastatic). VE1 was positive in 52% (38/73) of SBTs and 9% (2/22) of primary LGSCs, and in none of the mpSBTs and metastatic LGSCs (p<0.0001). Of 76 tumours with known mutation status, 42 (55%) harbored mutations, including BRAFV600E (26, 34%), KRASG12D (8, 11%), and KRASG12V (8, 11%). BRAFV600E mutations were present in 48% (25/52) of SBTs and 5% (1/22) of LGSCs (p<0.0001). VE1 was positive in 96% (25/26) of BRAFV600E-mutated tumours and correlated with BRAF mutation-associated histological features (p<0.0001). BRAFV600E mutations are significantly more common in SBTs than in LGSCs. Immunohistochemical expression of VE1 protein is strongly associated with BRAFV600E mutation and BRAF mutation-associated histological features. VE1 immunohistochemistry is a reliable method for the detection of BRAFV600E mutations.
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DOI：
10.1056/nejmoa1502309
发表时间：
2015-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hyman DM;Puzanov I;Subbiah V;Faris JE;Chau I;Blay JY;Wolf J;Raje NS;Diamond EL;Hollebecque A;Gervais R;Elez-Fernandez ME;Italiano A;Hofheinz RD;Hidalgo M;Chan E;Schuler M;Lasserre SF;Makrutzki M;Sirzen F;Veronese ML;Tabernero J;Baselga J
通讯作者：
Baselga J
影响因子：
7.2
作者：
Gershenson, David M.;Sun, Charlotte C.;Bodurka, Diane C.
通讯作者：
Bodurka, Diane C.
影响因子：
--
作者：
Sadlecki, Pawel;Walentowicz, Pawel;Walentowicz-Sadlecka, Malgorzata
通讯作者：
Walentowicz-Sadlecka, Malgorzata
影响因子：
7.3
作者：
Ardighieri, Laura;Zeppernick, Felix;Hannibal, Charlotte G.;Vang, Russell;Cope, Leslie;Junge, Jette;Kjaer, Susanne K.;Kurman, Robert J.;Shih, Ie-Ming
通讯作者：
Shih, Ie-Ming
影响因子：
3.3
作者：
Boesmueller, Hans;Fischer, Anna;Fend, Falko
通讯作者：
Fend, Falko