MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

Felipe Carrasco-Tenezaca; Theresa Marciano; Leanne M Brown; Gabrielle Carmichael; Guannan Gong; John Kunstman; David Klimstra; Pamela L Kunz; Po-Han Chen; Samuel G Katz

doi:10.1111/his.70273

PubMed · 42676111

MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

Felipe Carrasco-Tenezaca·Theresa Marciano·Leanne M Brown·Gabrielle Carmichael·Guannan Gong·John Kunstman·David Klimstra·Pamela L Kunz·Po-Han Chen·Samuel G Katz

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Abstract

INTRODUCTION: MET (c-MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET-targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes. METHODS AND RESULTS: Tissue microarrays containing well-differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H-score system. Different variables were assessed for H-score distribution and cross-tables. Survival analyses were conducted based on progression-free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H-scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (P < 0.05). When assessing different variables for higher MET H-scores, a significant association emerged at the 150-cut-off-point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H-score threshold of 200, high MET expression was significantly associated with shorter progression-free survival (mean 8.7 versus 13.4 years, P < 0.05) and overall survival (mean 3.6 versus 7.7 years, P < 0.05). CONCLUSION: Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti-MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.

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MET protein biomarkers human immunohistochemistry neuroendocrine tumours pancreatic neoplasms prognosis survival analysis tumour Journal Article

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Felipe Carrasco-Tenezaca, Theresa Marciano, Leanne M Brown, Gabrielle Carmichael, Guannan Gong, John Kunstman, David Klimstra, Pamela L Kunz, Po-Han Chen, Samuel G Katz. 2026-09-01. MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.. https://doi.org/10.1111/his.70273

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