AIMS: Secretory carcinoma (SC) of the salivary gland typically harbours ETV6-NTRK3 fusion, which can be utilised clinically to assist with diagnosis. Pan-Trk inhibitor therapy has demonstrated drastic responses in patients with NTRK-translocated tumours, including SC. Pan-Trk immunohistochemistry (IHC) is emerging as a sensitive and specific tool for detecting NTRK1, NTRK2 and NTRK3 fusions in various cancers. We aimed to establish the specificity and sensitivity of pan-Trk IHC in diagnosing SC and detecting ETV6-NTRK3 fusion. A literature review on the utility of pan-Trk IHC was conducted. METHODS AND RESULTS: Pan-Trk IHC was performed on 83 salivary gland neoplasms (29 SCs and 54 non-SCs). ETV6-NTRK3 fusion status was established in 25 cases. With any staining (nuclear or cytoplasmic) as a positive threshold, the sensitivity and specificity of pan-Trk IHC were 90% and 70% in diagnosing SC, and 100% and 0% in detecting NTRK3 fusion. When only pan-Trk nuclear staining was considered as positive, the sensitivity and specificity were 69% and 100% in diagnosing SC, and 92% and 100% in detecting NTRK3 fusion. CONCLUSIONS: Nuclear pan-Trk IHC is highly specific for SC diagnosis, with a specificity approaching 100%, making it a useful and precise diagnostic tool for differentiating SC from its histological mimics. On the other hand, any pan-Trk staining (nuclear or cytoplasmic) is highly sensitive for SC, and can serve as an attractive, cheap, fast and accessible screening tool for selecting patients to undergo confirmative molecular testing for clinical trials using TRK inhibitors.
AIMS: Secretory carcinoma (SC) of the salivary gland typically harbours ETV6-NTRK3 fusion, which can be utilised clinically to assist with diagnosis. Pan-Trk inhibitor therapy has demonstrated drastic responses in patients with NTRK-translocated tumours, including SC. Pan-Trk immunohistochemistry (IHC) is emerging as a sensitive and specific tool for detecting NTRK1, NTRK2 and NTRK3 fusions in various cancers. We aimed to establish the specificity and sensitivity of pan-Trk IHC in diagnosing SC and detecting ETV6-NTRK3 fusion. A literature review on the utility of pan-Trk IHC was conducted. METHODS AND RESULTS:Pan-Trk IHC was performed on 83 salivary gland neoplasms (29 SCs and 54 non-SCs). ETV6-NTRK3 fusion status was established in 25 cases. With any staining (nuclear or cytoplasmic) as a positive threshold, the sensitivity and specificity of pan-Trk IHC were 90% and 70% in diagnosing SC, and 100% and 0% in detecting NTRK3 fusion. When only pan-Trk nuclear staining was considered as positive, the sensitivity and specificity were 69% and 100% in diagnosing SC, and 92% and 100% in detecting NTRK3 fusion. CONCLUSIONS: Nuclear pan-Trk IHC is highly specific for SC diagnosis, with a specificity approaching 100%, making it a useful and precise diagnostic tool for differentiating SC from its histological mimics. On the other hand, any pan-Trk staining (nuclear or cytoplasmic) is highly sensitive for SC, and can serve as an attractive, cheap, fast and accessible screening tool for selecting patients to undergo confirmative molecular testing for clinical trials using TRK inhibitors.
Authors: Jaclyn F Hechtman; Ryma Benayed; David M Hyman; Alexander Drilon; Ahmet Zehir; Denise Frosina; Maria E Arcila; Snjezana Dogan; David S Klimstra; Marc Ladanyi; Achim A Jungbluth Journal: Am J Surg Pathol Date: 2017-11 Impact factor: 6.394
Authors: Elena Ardini; Maria Menichincheri; Patrizia Banfi; Roberta Bosotti; Cristina De Ponti; Romana Pulci; Dario Ballinari; Marina Ciomei; Gemma Texido; Anna Degrassi; Nilla Avanzi; Nadia Amboldi; Maria Beatrice Saccardo; Daniele Casero; Paolo Orsini; Tiziano Bandiera; Luca Mologni; David Anderson; Ge Wei; Jason Harris; Jean-Michel Vernier; Gang Li; Eduard Felder; Daniele Donati; Antonella Isacchi; Enrico Pesenti; Paola Magnaghi; Arturo Galvani Journal: Mol Cancer Ther Date: 2016-03-03 Impact factor: 6.261
Authors: Alena Skalova; Tomas Vanecek; Petr Martinek; Ilan Weinreb; Todd M Stevens; Roderick H W Simpson; Martin Hyrcza; Niels J Rupp; Martina Baneckova; Michael Michal; David Slouka; Tomas Svoboda; Alena Metelkova; Arghavan Etebarian; Jaroslav Pavelka; Steven J Potts; Jason Christiansen; Petr Steiner; Michal Michal Journal: Am J Surg Pathol Date: 2018-02 Impact factor: 6.394
Authors: Christian Rolfo; Rossana Ruiz; Elisa Giovannetti; Ignacio Gil-Bazo; Antonio Russo; Francesco Passiglia; Marco Giallombardo; Marc Peeters; Luis Raez Journal: Expert Opin Investig Drugs Date: 2015-10-12 Impact factor: 6.206
Authors: A Drilon; G Li; S Dogan; M Gounder; R Shen; M Arcila; L Wang; D M Hyman; J Hechtman; G Wei; N R Cam; J Christiansen; D Luo; E C Maneval; T Bauer; M Patel; S V Liu; S H I Ou; A Farago; A Shaw; R F Shoemaker; J Lim; Z Hornby; P Multani; M Ladanyi; M Berger; N Katabi; R Ghossein; A L Ho Journal: Ann Oncol Date: 2016-02-15 Impact factor: 32.976
Authors: Ramamoorthy Nagasubramanian; Julie Wei; Paul Gordon; Jeff C Rastatter; Michael C Cox; Alberto Pappo Journal: Pediatr Blood Cancer Date: 2016-04-19 Impact factor: 3.167
Authors: Bin Xu; Kartik Viswanathan; Kavita Umrau; Thair A D Al-Ameri; Snjezana Dogan; Kelly Magliocca; Ronald A Ghossein; Nicole A Cipriani; Nora Katabi Journal: Histopathology Date: 2022-09-05 Impact factor: 7.778
Authors: Samuel Rack; Laura Feeney; Brindley Hapuarachi; Helen Adderley; Laura Woodhouse; Guy Betts; George J Burghel; Kevin J Harrington; Robert Metcalf Journal: Cancers (Basel) Date: 2022-02-23 Impact factor: 6.639
Authors: G D Demetri; C R Antonescu; B Bjerkehagen; J V M G Bovée; K Boye; M Chacón; A P Dei Tos; J Desai; J A Fletcher; H Gelderblom; S George; A Gronchi; R L Haas; N Hindi; P Hohenberger; H Joensuu; R L Jones; I Judson; Y-K Kang; A Kawai; A J Lazar; A Le Cesne; R Maestro; R G Maki; J Martín; S Patel; F Penault-Llorca; C Premanand Raut; P Rutkowski; A Safwat; M Sbaraglia; I-M Schaefer; L Shen; C Serrano; P Schöffski; S Stacchiotti; K Sundby Hall; W D Tap; D M Thomas; J Trent; C Valverde; W T A van der Graaf; M von Mehren; A Wagner; E Wardelmann; Y Naito; J Zalcberg; J-Y Blay Journal: Ann Oncol Date: 2020-09-03 Impact factor: 32.976
Authors: Justin Bubola; Christina M MacMillan; Elizabeth G Demicco; Rose A Chami; Catherine T-S Chung; Iona Leong; Paula Marrano; Zeynep Onkal; David Swanson; Brandon M Veremis; Ilan Weinreb; Lei Zhang; Cristina R Antonescu; Brendan C Dickson Journal: Genes Chromosomes Cancer Date: 2021-07-08 Impact factor: 4.263