Tropomyosin Receptor Kinase A Expression on Merkel Cell Carcinoma Cells

Question  Is tropomyosin receptor kinase A expressed in Merkel cell carcinoma?

Findings  In this case series study, tropomyosin receptor kinase A expression on tumor cells was detected in every evaluable case of Merkel cell carcinoma.

Meaning  Expression of tropomyosin receptor kinase A on tumor cells in Merkel cell carcinoma may be a rationale for targeted therapy.

Importance  Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor frequently associated with the Merkel cell polyomavirus. Immune checkpoint therapy showed remarkable results, although not all patients are responsive to this therapy. Anti–tropomyosin receptor kinase A (TrkA)–targeted treatment has shown promising results in several tumor entities.

Objective  To determine TrkA expression in MCC as a rationale for potential targeted therapy.

Design, Setting, and Participants  This case series study investigated the MCC specimens of 55 patients treated at the Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany, from January 1, 2005, through December 31, 2015. Thirty-nine of the 55 samples were suitable for further histopathologic examination. Expression of TrkA was explored by immunohistochemical analysis.

Exposure  Diagnosis of MCC was confirmed by staining positive for cytokeratin 20 (CK20) and synaptophysin.

Main Outcomes and Measures  Expression of TrkA on the tumor cells.

Results  Specimens of 39 patients (21 women and 18 men; mean [SD] age, 75.0 [7.8] years) underwent immunohistochemical investigation. Thirty-eight of 38 specimens expressed CK20 and synaptophysin on the MCC tumor cells (100% expression). Merkel cell polyomavirus was detected in 32 of 38 specimens (84%). Tropomyosin receptor kinase A was found in all 36 evaluable specimens on the tumor cells; 34 (94%) showed a weak and 2 (6%) showed a strong cytoplasmic expression. In addition, strongly positive perinuclear dots were observed in 30 of 36 specimens (83%).

Conclusions and Relevance  Tropomyosin receptor kinase A was expressed on MCC tumor cells in 100% of evaluable specimens. This result may lead to the exploration of new targeted treatment options in MCC, especially for patients who do not respond to anti–programmed cell death protein 1 treatment.