Neurotrophic tyrosine receptor kinase (NTRK) 1 and 2 expression in squamous cell carcinoma and squamous intraepithelial lesions of the cervix uteri

Background: Selective tropomyosin receptor kinase (Trk) inhibitors are known to provide promising outcomes in selected tumor patients with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. In the present study, we aimed to determine whether there was a NTRK1 and NTRK2 expression in cervical squamous cell carcinoma (SCC) and precursor lesions. Materials and methods: A total of 92 formalin-fixed paraffin-embedded tissue samples of cervical SCC, squamous intraepithelial lesion (SIL) and non-neoplastic cervical tissue (NCT) were subjected to immunohistochemical (IHC) staining with NTRK1 and NTRK2 antibodies. These stainings were compared with p16/Ki-67 (IHC) and the low-risk/high-risk Human papillomavirus (HPV) in situ hybridization stainings that were previously administered. Results: In IHC analysis, NTRK1 expression was detected in 3.2% and 12.5% of SCC and cervical intraepithelial neoplasia (CIN)-2 samples, respectively. In addition, NTRK2 expression was detected in 6.5% and 6.3% of SCC and CIN-2 samples, respectively. However, NTRK1/NTRK2 expression was not detected in samples of NCT, CIN-1, and CIN-3. The p16 and Ki-67 expression and high-risk HPV positivity increased as the grade of the lesion increased. Conclusions: The results indicated that both NTRK1 and NTRK2 had no contributory effect on the grading and differentiation of cervical SCC and SIL. We consider that the IHC method is likely to be used for the screening of NTRK gene fusions in patients with cervical SCC. Trk inhibitors are likely to be a favorable therapeutic alternative for this low number of SCC cases with positive NTRK1/NTRK2 staining. Further studies are needed to confirm these ideas.

Cervix uteri; NTRK1; NTRK2; Squamous cell carcinoma; Squamous intraepithelial lesion

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