Biomarker NTRK Coverage from Every Angle

Gastrointestinal Malignancies: Biomarker Analysis Via Immunohistochemistry

By: Vanessa A. Carter, BS
Posted: Monday, January 10, 2022

Matthew W. Rosenbaum, MD, and Raul S. Gonzalez, MD, both of Beth Israel Deaconess Medical Center, Boston, published their review on predictive and prognostic biomarkers for gastrointestinal malignancies in Seminars in Diagnostic Pathology. These biomarkers can be identified via immunohistochemical analysis, which are chosen based upon various scoring criteria, staining rationale, pictorial examples, and associated systemic therapies. In this largely organ-based review, multiple immunohistochemical techniques were identified for their respective cancer types.

“Biomarkers currently play a more limited role in evaluation of pancreatic and small bowel malignancies,” the study authors commented. “Immunohistochemistry can also be used to evaluate biomarker status in gastrointestinal stromal tumors, gastrointestinal malignancies with NTRK gene fusions, and undifferentiated carcinomas with switch-sucrose non-fermentable complex abnormalities.”

The most commonly utilized type of immunohistochemistry in esophageal squamous cell carcinoma is PD-L1 staining. Tumor cells that express PD-L1 can escape immune attack, but PD-1 inhibitors can be used to disrupt this interaction. EGFR, ERBB2, HER2, and mismatch repair are other potential biomarkers, as their overexpression in esophageal carcinoma is associated with a poor prognosis.

The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend mismatch repair and PD-L1 evaluation in locally advanced pancreatic ductal adenocarcinoma, as to suggest PD-1 inhibitor therapy. Often, pancreatic neuroendocrine neoplasms are graded via the use of Ki67 immunohistochemistry, as it indirectly acts as a prognostic marker. CK19 is also a potential biomarker of these tumors and has been reported to correlate with a poor prognosis.

NTRK gene fusions are rare and can occur in a wide variety of malignant neoplasms, but they can be targeted with larotrectinib, which inhibits tropomyosin kinase receptors TrkA, TrkB, and TrkC. The pan-TRK immunohistochemical stain can detect these fusions, as cytoplasmic expression is notably reported across all fusions. Furthermore, immunohistochemistry can also be used to screen for malignancies involving tumor suppressors, such as p53 and the switch-sucrose non-fermentable complex.

Disclosure: The study authors reported no conflicts of interest.

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