MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours

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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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