A rare case of recurrent ovarian cancer with TPM3-NTRK1 gene rearrangement: A case report

NTRK gene fusion is rare in gynecological cancer. Entrectinib is a novel targeted drug, which is a potent inhibitor of TRK A, B and C. The present case report described a case of recurrent ovarian cancer with TPM3-NTRK1 rearrangement, which was detected by next-generation sequencing (NGS) and treated with entrectinib. A 56-year-old woman was diagnosed as having stage IV ovarian cancer with positive pleural fluid cytology. Neoadjuvant chemotherapy and interval debulking surgery, followed by chemotherapy, were performed. A total of 10 months after completion of chemotherapy, the disease recurred and the patient was treated with multimodal therapy for recurrence. DNA-based NGS detected TPM3-NTRK1 rearrangement and entrectinib therapy was initiated; however, the disease progressed despite 6 weeks of entrectinib administration, and 1 month after discontinuation of entrectinib, the patient died. After their death, immunohistochemistry with a pan-Trk monoclonal antibody was performed to determine the expression levels of TRK; however, immunohistochemistry was negative for TRK. In conclusion, the present case report described a rare case of recurrent ovarian cancer with TPM3-NTRK1 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA-based NGS, immunohistochemistry was negative for TRK. These findings indicated that immunohistochemistry may be required for confirmation of TRK protein expression prior to entrectinib administration.

Automated summary

This case report describes a rare case of recurrent ovarian cancer with TPM3-NTRK1 gene fusion that was not responsive to Entrectinib treatment. Immunohistochemistry showed negative expression of TRK protein, suggesting the need for immunohistochemistry confirmation prior to Entrectinib administration.