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TRK Expression and Molecular Characteristics of Gene Fusions in Primary Liver Carcinomas

By: Julia Fiederlein
Posted: Thursday, July 14, 2022

Dongwei Zhang, MD, PhD, and Xiaoyan Liao, MD, PhD, both of the University of Rochester Medical Center, New York, conducted a study to investigate the TRK protein expression and molecular characteristics of gene fusions in primary liver carcinomas. Their findings were published in the journal Applied Immunohistochemistry & Molecular Morphology.

NTRK [gene] fusion is very rare in primary liver carcinomas,” the investigators commented. “Immunohistochemistry on tissue microarray for TRK expression yields high false-positive results, which should be validated on whole sections and confirmed by molecular genetic studies such as RNA sequencing.”

Surgically resected primary liver carcinoma specimens (hepatocellular carcinoma: n = 110; intrahepatic cholangiocarcinoma: n = 69) were obtained for tissue microarray construction and clinicopathologic characterization. The investigators initially performed pan-TRK immunohistochemistry on tissue microarray slides; staining intensity (negative, weak, moderate, or strong) and localization (cytoplasmic or nuclear) were evaluated.

Based on the results of immunohistochemistry on tissue microarray, 12 patients with hepatocellular carcinoma (10.9%) demonstrated weak cytoplasmic TRK expression; all others, including those with intrahepatic cholangiocarcinoma, tested negative for TRK expression. Age, sex, tumor differentiation, and tumor stage did not seem to correlate with TRK expression. Each of the 12 cases was found to be negative for TRK expression upon immunohistochemical validation on whole sections.

RNA sequencing analysis did not detect NTRK gene fusions in the 12 hepatocellular carcinoma cases, but fusions involving genes encoding mitochondrial and ribosomal proteins, microRNAs, and transcription factors were identified; according to the investigators, this finding may warrant further study. Among those gene fusions, a few were recurrent: mitochondrial gene MT-ATP6/MT-ATP8 fusion (75.0%); immunoglobulin κ light chain gene IGKV/IGKJ fusion (41.7%); and histocompatibility complex gene HLA-C/HLA-B fusion (33.3%).

Disclosure: The study authors reported no conflicts of interest.

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