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NTRK Gene Fusions and TRK Protein Expression in Merkel Cell Carcinoma

By: Vanessa A. Carter, BS
Posted: Friday, January 13, 2023

According to Rocco Cappellesso, MD, of Padua University Hospital, Italy, and colleagues, there are currently no data available about NTRK alterations in neuroendocrine tumors of the skin, such as Merkel cell carcinoma, even though its molecular landscape has been extensively investigated. Published in the International Journal of Molecular Sciences, a retrospective study aimed to evaluate the expression of tyrosine kinase (TRK) proteins in Merkel cell carcinoma to verify the potential association among NTRK fusions, clinicopathologic features, and survival.

“TRK expression is not involved in Merkel cell carcinoma carcinogenesis and tumor progression, since it was not associated with prognostic and clinicopathological features, except for the nuclear localization of the receptor in Merkel cell polyomavirus–negative tumors,” the investigators concluded. “Future larger multicentric studies should explore the gene-fusion landscape of Merkel cell carcinoma, since data are lacking in the literature.”

This study included tumor samples of 76 patients who were diagnosed with Merkel cell carcinoma at the Veneto Institute of Oncology or Padua University Hospital from 2001 to 2019. A pathologist reviewed and confirmed the diagnoses of all cases.

A positive pan-TRK immunoreaction was identified in 34 cases, which included single localization in 11 cases and multiple localizations in the remaining cases. Moreover, pan-TRK immunostaining was cytoplasmic; membranous; dot-like; and nuclear in 29, 19, 10, and 6 tumors, respectively. Of note, fusions involving NTRK1, NTRK2, or NTRK3 were not detected in any of the 76 cases through RNA-based next-generation sequencing, fluorescence in situ hybridization, or real-time polymerase chain reaction.

Although nuclear pan-TRK immunostaining correlated with Merkel cell polyomavirus negativity (P = .02), it was not dependent on gender, age, or primary site. The median overall survival was 31 months, with 32 patients experiencing clinical upstaging, tumor recurrence, or disease progression. With a 3-year overall survival rate of 53%, the 3-year rate of recurrence or progression-free survival was 52%.

Disclosure: The study authors reported no conflicts of interest.


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