Article
Metastatic Gastroenteropancreatic Neuroendocrine Tumors: The Revised WHO Classification and its Correlation with Somatostatin Analog Uptake
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Published: | March 20, 2006 |
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Outline
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Radiolabeled somatostatin analogs allow efficient imaging and targeting of metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET). Despite successful establishment of the revised WHO classification which distinguishes between low and high grade malignant GEP NET, there is a lack of scintigraphic studies comparing uptake behaviour on the basis of this categorization. This study aims to define predisposing factors of somatostatin receptor mediated tracer uptake implementing the updated tumor criteria of the current WHO classification.
Methods: 57 consecutive patients with histologically confirmed metastatic GEP NET evaluated with In-111-pentetreotide (Oct) were included in this study. Tumors were categorized according to the revised WHO classification. Ki67 indices of high grade tumors in this patient group were ranging between 20% – 75%. Intensity of tracer uptake was graded according to the different metastatic regions and patients were then rated as tracer positive or negative depending on the uptake in the clinically relevant tumor lesions. Correlation was tested between the proportion of positive patients and tumor origin, function and malignancy.
Results: Overall, 52 patients (91.2%) were strongly Oct positive. The proportion of Oct positive patients was significantly higher (p=0.01) in low than high grade malignant tumors. Functionality provided a borderline significant association with tracer uptake before exclusion of the high grade tumors, while examination of the low grade carcinomas revealed no influence of functionality on tracer uptake (p=0.21). 60% of Oct negative patients had high grade carcinomas (GEP NET type 2) compared to 7.7% of Oct positive patients.
Conclusion: Somatostatin analog affinity is observed with high frequency in patients with metastatic GEP NET throughout the different subgroups. Based on the revised WHO classification the only significant influencing factor for this receptor mediated tracer uptake is tumor differentiation. Negative somatostatin analog radioimaging in metastatic GEP NET raises the suspicion of potential high grade malignancy, providing implications for patient management and selection for targeted therapy.