Immunohistochemical expression of pan-Trk in a large cohort of salivary gland neoplasms: preliminary results

Abstract

<h3>Introduction</h3> Neurotrophic tyrosine receptor kinases (NTRK) represent a group of proteins that actively partici- pate in cell survival, proliferation, and differentiation processes. NTRK gene rearrangements have been identified in several neoplasms, including secretory carcinoma of the salivary glands (ETV6-NTRK3). A newly developed pan-Trk antibody for immunohistochemistry (IHC) was able to identify and differentiate cases of secretory carcinoma from mimics by its nuclear staining. However, different patterns of expression (cytoplasmic and/or membranous) have also been reported in benign and malignant salivary gland neoplasms (SGN). Due to this apparent heterogeneous staining profile, the significance of pan-Trk IHC in SGN is still unclear. <h3>Materials and Methods</h3> Cases of salivary mucoepidermoid carcinoma (MEC), polymorphous adenocarcinoma (PAC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), epithelial-myoepithelial carcinoma (EMC), and secretory carcinoma (SC) were retrieved be- tween 2003 and 2019 from the University of Iowa, College of Dentistry archives. Pan-Trk IHC was performed in tissue microarrays. IHC pattern of expression and intensity (H-score) were assessed. <h3>Results</h3> Patient cohort was comprised of 41 women and 20 men with a median age of 61 years old. The most common location was the palate followed by the buccal mucosa. Pan-Trk is positive predominantly in the nucleus of SC (H-score=23.6), and in the cytoplasm/membrane of PAC (H-score=12.2), MEC (H-score=5.6), AdCC (H-score=13.5), and EMC (Hscore=21.4). How- ever, nuclear staining was also present in a small subset of PAC, MEC, and AdCCs. Notably, Pan-Trk was negative in all ACC samples. <h3>Conclusions</h3> Preliminary data suggests that pan-Trk nuclear staining is not exclusive to SC. Fur- thermore, the cytoplasmic/membranous pattern seen in non-SC neoplasms may indicate the presence of NTRK gene rearrangement. A better understanding about the pan-Trk staining pattern could not only improve its diagnostic value, but also contribute identifying patients that would benefit from targeted-therapies using NTRK inhibitors (<i>e.g.</i> entrectinib, larotrectinib).