New Pathological Insights into Biomarkers for Multimodal Therapeutic Approach in Hepatic Neuroendocrine Tumors: A...

Neuroendocrine tumors (NETs) represent a complex, heterogeneous group of cancers with unique characteristics. Early detection and multiple modalities therapies such as surgical intervention or symptom control (e.g., somatostatin analogs). Treatment for late-stage disease including combining local treatment (surgery, radiofrequency ablation, selective internal radiation therapy, trans-hepatic arterial chemo-embolization/trans-hepatic arterial embolization) with that for systemic disease, such as peptide receptor radionuclide therapy, chemotherapy and targeted therapy, are essential for managing symptoms and improving outcomes. Current biomarkers for neuroendocrine tumors including chromogranin A, synaptophysin, Ki-67, somatostatin receptors, mammalian target of rapamycin, vascular endothelial growth factor and its receptor, and O ⁶-methylguanine-DNA methyl transferase are important in diagnosis and treatment of NETs.

We report a rare case of multifocal primary hepatic neuroendocrine tumor (WHO grade 2) in a 79-year-old male. Due to tumor progression under octreotide therapy and the risk of rupture, a multimodal therapeutic approach was implemented. This included initial transcatheter arterial chemoembolization, followed by left lateral hepatectomy and wedge resection combined with intraoperative radiofrequency ablation. Surgical specimens were analyzed for CDK5 and p35 expression. The patient recovered well without complications and was discharged on postoperative day 9.

In this case, cyclin-dependent kinase 5 (CDK5) and its activator, p35, were identified as potential novel biomarkers in NET. The differential expression of CDK5 and p35 observed in tumors of varying sizes suggests a correlation with tumor progression. These findings highlight the potential of the CDK5/p35 pathway as a therapeutic target for the management of advanced or metastatic NET.