Performance of DAXX immunohistochemistry as a screen for DAXX mutations in pancreatic neuroendocrine tumors Journal Article
| Authors: | Hechtman, J. F.; Klimstra, D. S.; Nanjangud, G.; Frosina, D.; Shia, J.; Jungbluth, A. A. |
| Article Title: | Performance of DAXX immunohistochemistry as a screen for DAXX mutations in pancreatic neuroendocrine tumors |
| Abstract: | Objectives DAXX immunohistochemistry (IHC) is often used as a surrogate for sequencing. We aimed to elucidate the sensitivity of IHC for DAXX mutation. Methods 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. Results 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%). Conclusions 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. © 2019 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | immunohistochemistry; pancreatic neuroendocrine tumor; daxx; next generation sequencing; alternative lengthening of telomeres |
| Journal Title: | Pancreas |
| Volume: | 48 |
| Issue: | 3 |
| ISSN: | 0885-3177 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2019-03-01 |
| Start Page: | 396 |
| End Page: | 399 |
| Language: | English |
| DOI: | 10.1097/mpa.0000000000001256 |
| PUBMED: | 30747827 |
| PROVIDER: | scopus |
| PMCID: | PMC6414083 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2019 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work