Detection of NTRK Fusions and TRK Expression and Performance of pan-TRK Immunohistochemistry in Routine Diagnostics: Results from a Nationwide Community-Based Cohort

Diagnostics

卷:12

Wim Timens¹  Léon C. van Kempen¹  Ed Schuuring¹  Stefan M. Willems¹  Bart Koopman¹  Harry J. M. Groen²  Chantal C. H. J. Kuijpers³ 

[1] Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands;

[2] Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands;

[3] Foundation PALGA, De Bouw 123, 3991 SZ Houten, The Netherlands;

关键词: NTRK;    TRK;    fusion;    nationwide;    molecular diagnostics;    routine;   

DOI  :  10.3390/diagnostics12030668

来源: DOAJ

【 摘 要 】

Gene fusions involving NTRK1, NTRK2, and NTRK3 are rare drivers of cancer that can be targeted with histology-agnostic inhibitors. This study aimed to determine the nationwide landscape of NTRK/TRK testing in the Netherlands and the usage of pan-TRK immunohistochemistry (IHC) as a preselection tool to detect NTRK fusions. All pathology reports in 2017–2020 containing the search term ‘TRK’ were retrieved from the Dutch Pathology Registry (PALGA). Patient characteristics, tumor histology, NTRK/TRK testing methods, and reported results were extracted. NTRK/TRK testing was reported for 7457 tumors. Absolute testing rates increased from 815 (2017) to 3380 (2020). Tumors were tested with DNA/RNA-based molecular assay(s) (48%), IHC (47%), or in combination (5%). A total of 69 fusions involving NTRK1 (n = 22), NTRK2 (n = 6) and NTRK3 (n = 41) were identified in tumors from adult (n = 51) and pediatric (n = 18) patients. In patients tested with both IHC and a molecular assay (n = 327, of which 29 NTRK fusion-positive), pan-TRK IHC had a sensitivity of 77% (95% confidence interval (CI), 56–91) and a specificity of 84% (95% CI, 78–88%). These results showed that pan-TRK IHC has a low sensitivity in current routine practice and warrants the introduction of quality guidelines regarding the implementation and interpretation of pan-TRK IHC.

【 授权许可】

Unknown