TRK immunohistochemistry in pediatric rhabdomyosarcomas: diagnostic and prognostic utility and limitations

Rhabdomyosarcoma is the third most common extracranial solid tumor in childhood. Treatment of patients is multimodal, based on systemic chemotherapy and local therapy by surgery and/or radiotherapy. Although standard therapies result in an overall survival of more than 75% for patients in the low-risk group, the prognosis for high-risk patients remains poor. For this reason, new therapeutic alternatives are needed. One such option is the use of specific Tropomyosin receptor kinase (TRK) inhibitors, which provides the opportunity of targeted therapeutic treatment for patients carrying Neurotrophic Receptor Tyrosine Kinase (NTRK) translocations. As the frequency of these aberrations is not yet known in rhabdomyosarcomas, the aim of this study was to map the pan-TRK expression profile of rhabdomyosarcomas by an affordable method and to investigate the link between the expression and the clinicopathological features. We studied samples of patients diagnosed with rhabdomyosarcoma at the Pediatric Center, Semmelweis University, Budapest, Hungary. Using immunohistochemistry, we found that pan-TRK expression was detected in 38% of the cases studied. The expression was present in a significantly higher proportion of samples in the unfavorable, alveolar histological subtype. However, no NTRK fusion was detected in the 17 TRK expressing samples.