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Objective: Pancreatic endocrine tumors (PETs) are characterized by the presence of hormone syndromes. Reports focusing on calcitonin-secreting PET (CTsPETs) are very rare. This study aimed to define a CTsPET-associated syndrome in regard to chemical, anatomical, and developmental aspects., Methods: A computerized MEDLINE search was conducted under the search items: "pancreatic endocrine tumor," "calcitonin," "neuroendocrine pancreatic tumor," and "pancreas." Results of clinical, histopathological, immunohistochemical, and biochemical assessments of all patients identified with CTsPET were registered and statistically analyzed., Results: Thirty-seven patients with CTsPET were identified. Mean serum calcitonin was elevated to the 89.2-fold of the upper reference value. Main symptoms were watery diarrhea (51.4%) and abdominal pain (35.1%). Most patients (59.5%) presented with metastatic spread at the time of diagnosis. Of all patients, 66.7% were alive after a mean follow-up of 28.9 months. Survival was higher in patients who underwent more aggressive surgical therapies independent from tumor sizes and in those with no metastases at the time of diagnosis., Conclusions: High calcitonin levels should always raise suspicion of medullary thyroid carcinomas. However, when thyroid examination remains without pathological findings, a CTsPET should be excluded. An aggressive surgical approach even in cases with large primary tumor sizes may lead to a longer survival.

Objectives: Tissue inhibitor of metalloproteinase-3 (TIMP3) antagonizes matrix metalloproteinase activity and can suppress tumor growth, angiogenesis, invasion, and metastases. In the present study, the involvement of TIMP3 in the tumorigenesis of 34 pancreatic adenocarcinomas was evaluated., Methods: Immunohistochemistry, methylation-specific PCR, and RNA expression analysis (RT-PCR) of TIMP3 were performed in 34 resected and microdissected primary pancreatic adenocarcinomas., Results: Immunohistochemistry showed loss or strongly reduced protein expression in 17 of 34 pancreatic adenocarcinomas (50%) that corresponded to loss of TIMP3-RNA-expression. Promoter hypermethylation was identified in 2 of 34 tumors (6%). It was tumor specific and corresponded to a loss of TIMP3 protein expression. TIMP3 alterations did not correlate with any clinical feature such as tumor size or survival., Conclusion: TIMP3 seems to play an important role in the tumorigenesis of primary pancreatic adenocarcinomas. In contrast to other tumors, hypermethylation seems not to be the key mechanism for the inactivation of TIMP3. Other methods of gene inactivation need to be identified.