Hechtman Jaclyn F, Klimstra David S, Nanjangud Gouri, Frosina Denise, Shia Jinru, Jungbluth Achim A
From the Department of Pathology and.
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY.
Pancreas. 2019 Mar;48(3):396-399. doi: 10.1097/MPA.0000000000001256.
DAXX immunohistochemistry (IHC) is often used as a surrogate for sequencing. We aimed to elucidate the sensitivity of IHC for DAXX mutation.
All pancreatic neuroendocrine tumors (PanNETs) with DAXX mutations detected by sequencing and a subset of DAXX wild-type PanNETs were analyzed for DAXX expression by IHC.
Of 154 PanNETs with MSK-IMPACT testing, 36 (30%) harbored DAXX mutations. DAXX mutations were associated with TSC2 mutations (46% vs 10%, P < 0.0001), tended to co-occur with MEN1 mutations (63% vs 49%, P = 0.11), and tended to be mutually exclusive with ATRX mutations (11% vs 25%, P = 0.053). Of 27 available DAXX mutant PanNETs, 23 lost DAXX expression (85.2%). All 4 DAXX mutants with retained expression harbored DAXX mutations within the SUMO-interacting motif of the last exon. Telomere-specific fluorescence in situ hybridization demonstrated alternative lengthening of telomeres in all 4 cases. Of 20 PanNETs with wild-type DAXX, 19 retained DAXX IHC expression (95%).
The sensitivity and specificity of IHC for DAXX mutation are 85% and 95%, respectively. Last exon DAXX mutant PanNETs often show alternative lengthening of telomeres despite retained DAXX expression, likely due to escape of nonmediated decay.
死亡结构域相关蛋白（DAXX）免疫组化（IHC）常被用作测序的替代方法。我们旨在阐明IHC检测DAXX突变的敏感性。
对所有经测序检测出DAXX突变的胰腺神经内分泌肿瘤（PanNETs）以及一部分DAXX野生型PanNETs进行IHC分析，以检测DAXX表达情况。
在154例接受纪念斯隆凯特琳癌症中心（MSK）-IMPACT检测的PanNETs中，36例（30%）存在DAXX突变。DAXX突变与结节性硬化症2型（TSC2）突变相关（46%对10%，P<0.0001），倾向于与多发性内分泌腺瘤1型（MEN1）突变同时出现（63%对49%，P = 0.11），并且倾向于与α-地中海贫血/智力低下综合征X连锁基因（ATRX）突变相互排斥（11%对25%，P = 0.053）。在27例可获得的DAXX突变型PanNETs中，23例DAXX表达缺失（85.2%）。所有4例DAXX表达保留的突变体在最后一个外显子的小泛素样修饰蛋白（SUMO）相互作用基序内存在DAXX突变。端粒特异性荧光原位杂交显示所有4例均存在端粒替代延长。在20例DAXX野生型PanNETs中，19例DAXX IHC表达保留（95%）。
IHC检测DAXX突变的敏感性和特异性分别为85%和95%。尽管DAXX表达保留，但最后一个外显子DAXX突变型PanNETs通常显示端粒替代延长，可能是由于非介导衰变逃逸所致。
