Biomarker NTRK Coverage from Every Angle

Positivity and Translocations of FGFR2 and NTRK1 in Intrahepatic Cholangiocarcinoma

By: Vanessa A. Carter, BS
Posted: Sunday, August 1, 2021

During the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021, Yuan Ji, MD, PhD, of Zhongshan Hospital Fudan University, Shanghai, China, and a colleague presented their findings on the status of NTRK1 and FGFR2 genes in intrahepatic cholangiocarcinoma—a subtype of primary liver cancer lacking effective treatment options—and how they may relate to clinicopathologic features (Abstract 353). Based on their immunohistochemistry and fluorescence in situ hybridization data, a substantial subgroup of patients with NTRK- and FGFR2-positive cancers may ultimately be eligible for targeted therapy.

The investigators collected samples from 160 patients who underwent surgical resection for intrahepatic cholangiocarcinoma. NTRK1 and FGFR2 protein expression was analyzed by immunohistochemistry, whereas their gene translocations were examined by fluorescence in situ hybridization.

About 13.2% of intrahepatic cholangiocarcinomas demonstrated FGFR2-positive status and had FGFR2 translocations. Positivity in these patients tended to correlate with low histologic grade, less mucus (P = .024), a lower preoperative serum CA199 level (P < .01), and a higher frequency of hepatitis B infections (P < .01). Interestingly, patients with FGFR2 translocation manifested a small duct subtype and displayed a better median overall survival than those with normal FGFR2 (57 vs. 33 months).

An NTRK1 translocation was observed in nine patients, four of whom had hepatitis B, and six demonstrated a large duct subtype. Two patients with an NTRK1 translocation showed moderately positive immunohistochemistry, with the rest being weak or negative. Three patients with FGFR2 translocation showed moderate to strong positive immunohistochemistry.

FGFR2 and NTRK1 translocations by fluorescence in situ hybridization were found in two patients. Rates of concordance between fluorescence in situ hybridization and immunohistochemistry were 14.3% for FGFR2 and 22.2% for NTRK1, respectively. The positive rate by immunohistochemistry was significantly lower than that by fluorescence in situ hybridization for both FGFR2 (3.7% vs. 13%) and NTRK1 (2.5% vs. 5%).

Disclosure: The study authors reported no conflicts of interest.

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