Prostatic adenocarcinoma with novel NTRK3 gene fusion: a case report

Abstract

TMPRSS2-ERG gene fusion occurs in approximately 50% of prostatic adenocarcinoma and their expression is associated with aggressive phenotype, higher tumor stage, and tumor metastasis. A case of prostatic adenocarcinoma with IRF2BP2-NTRK1 translocation was previously reported. We report a prostatic adenocarcinoma with novel NTRK3 gene fusion that occurs in a 71-year-old male patient with aggressive histologic phenotype and multiple bony metastases. Prostatic biopsy revealed that there is a prostatic adenocarcinoma with a Gleason score of 9 (4+5), grade group 5, and multiple sites of perineural and ganglional invasion. Fluorescence in-situ hybridization (FISH) and next-generation sequencing were performed. FISH studies showed a breakage within the NTRK3 gene in prostatic adenocarcinoma cells. Next-generation sequencing confirmed that there is a PRPSAP1-NTRK3 translocation in the prostatic adenocarcinoma. In addition, ASXL1, KIF5B, MED12, PIK3CA mutations were found. NTRK alterations or dysregulation of PI3K signaling pathway were found in many types of cancers. TRK inhibitors including larotrectinib and entrectinib were approved by the US Food and Drug Administration for treating TRK fusion-positive malignant tumors and PI3K/AKT/mTOR pathway inhibitors were under clinical studies on various cancers including prostate cancer. In our current case, both NTRK3 and PIK3CA may serve as biomarkers for precision targeted therapy.

Keywords: NTRK3; PI3K; PIK3CA; PRPSAP1-NTRK3; Prostatic adenocarcinoma; TMPRSS2-ERG; translocations.

Figure 1

Histopathological features of prostatic adenocarcinoma. A. The prostatic core shows 80% involvement by prostatic adenocarcinoma, Gleason score 9 (4+5), grade group 5 (H&E, 40×). B. The prostatic carcinomas are composed of fusion glands arranged in a cribriform pattern (H&E, 100×). C. The adenocarcinoma cells are characterized by hyperchromatic nuclei containing one or more nucleoli, consistent with Gleason pattern 4 (H&E, 400×). D. Focal areas of adenocarcinoma show dispersed carcinoma cells with hyperchromatic nuclei and scanty cytoplasm, consistent with Gleason pattern 5 (H&E, 400×). E. Multiple areas demonstrate perineural invasion (H&E, 200×). F. Invasion of ganglional cells is evident (H&E, 400×).

Figure 2

Fluorescence in-situ hybridization (FISH) of NTRK3 “break-apart” probe. A. The red signal (yellow arrows) shows that the NTRK3 “break-apart” FISH probe targeting the 3’ terminal region. B. The green signal (yellow arrow) reveals that the NTRK3 “break-apart” FISH probe targeting the 5’ terminal region. C. The blue staining represents DAPI nuclear stain. D. The red and green signals (yellow arrows) demonstrate the two separately located NTRK3 “break-apart” FISH probes. These results indicate a breakage of the NTRK3.