Deregulation of EGFR/VEGF/HIF-1a signaling pathway in colon adenocarcinoma based on tissue microarrays analysis.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in colon adenocarcinoma (CA) is a frequent event, whereas specific deregulation mechanisms in the corresponding signaling pathways remain under investigation. Our aim was to co-evaluate their expression correlated to the hypoxia inducible factor 1alpha (HIF-1a), which activates the transcription of VEGF gene. METHODS: 60 paraffin-embedded primary CAs were cored at 1.5 mm diameter and transferred to the microarray block. Immunohistochemistry (IHC) was performed using anti-EGFR, -VEGF, and -HIF 1a monoclonal antibodies. Concerning EGFR, quantitative evaluation was based on a semi-automated analysis system. Chromogenic in situ hybridization (CISH) was performed using EGFR gene and chromosome 7 centromeric probes. RESULTS: Protein overexpression was observed in 13/60 (21.6%), 45/60 (75%) and 7/60 (11.6%) cases regarding EGFR, VEGF, and HIF 1a, respectively. CISH analysis detected 4/60 (6.6%) EGFR gene amplified cases, whereas chromosome 7 aneuploidy was identified in 11/60 (18.3%) cases. Significant associations raised correlating stage to chromosome 7 (p=0.024), HIF 1a expression to tumor anatomical location (p=0.019) and also VEGF to HIF 1a expression (p=0.001), whereas EGFR expression was not associated to EGFR gene copies. CONCLUSION: According to our results, chromosome 7 instability is correlated to advanced disease, whereas a significant subset of CAs demonstrates an alternative, non- HIF 1a depended mechanism of VEGF overexpression. Furthermore, EGFR protein overexpression does not predict a specific gene deregulation mechanism.

Acinar cell carcinoma of the pancreas with and without endocrine differentiation.

BACKGROUND: Acinar cell carcinoma (ACC) is a rare pancreatic neoplasm, representing 1% of exocrine tumours and containing a variable endocrine component. Three recent cases of ACC are reported. CASE OUTLINES: A 72-year-old man with painless obstructive jaundice had a 5-cm mass in the head of pancreas resected by Whipple's operation; histopathological examination showed a typical ACC. A 33-year-old man with weight loss and abnormal liver function had a dilated biliary tree but no mass on imaging. Pylorus-preserving pancreatoduodenectomy was performed, and histology showed a mixed acinar-neuro-endocrine tumour. A 56-year-old man with weight loss and a palpable mass had a 15-cm mass in the distal body of pancreas, which was resected en bloc with the spleen and adherent stomach; it was a cystic ACC. RESULTS: Two patients are alive and free of disease at 30 months and 15 months, while the third patient with locally advanced disease died of myocardial infarction at 9 weeks. DISCUSSION: Acinar structures are the hallmark of this neoplasm, which carries a better survival rate than ductal cancer. Surgical excision prolongs survival and offers the best chance of cure.

Parathyroid hormone-related peptide in pancreatic neuroendocrine tumours associated with hypercalcaemia.

BACKGROUND: Hypercalcaemia is a common paraneoplastic syndrome. In the context of pancreatic neuroendocrine tumours, it is occasionally caused by secretion of parathyroid hormone-related peptide (PTH-rP). CASE OUTLINES: Two patients are reported in whom persistent hypercalcaemia was traced to a large neuroendocrine pancreatic tumour hypersecreting PTH-rP. Resection of the tumour reduced serum levels of calcium and PTH-rP transiently in each case until the patient developed bulky metastatic disease. A 33-year-old woman remained hypercalcaemic after the removal of all four hyperplastic parathyroid glands had rendered circulating parathormone levels undetectable. Radical distal pancreatectomy was followed over the next 4 years by operative debulking of liver metastases, multiple hepatic artery embolisations, octreotide injections and repeated admissions for intravenous fluid and biphosphonate therapy. A 41-year-old man presented with hypercalcaemia as well as features of somatostatinoma syndrome. Symptomatic improvement after radical distal pancreatectomy was short-lived, and hepatic artery embolisation failed to control his rapidly progressive disease. DISCUSSION: Malignant hypercalcaemia associated with a neuroendocrine pancreatic tumour hypersecreting PTH-rP is difficult to treat and can be life-threatening. Aggressive surgical treatment is recommended initially, while somatostatin analogues and hepatic artery embolisation are alternative therapeutic options for metastatic disease.

Magnesium deficiency in patients with chronic pancreatitis identified by an intravenous loading test.

Magnesium deficiency is a common clinical condition that may exist despite a normal serum magnesium concentration. Patients with chronic pancreatitis could develop magnesium deficiency due to either malabsorption, diabetes mellitus, or chronic alcoholism. Since serum levels of magnesium are a poor indicator of magnesium deficiency, the retention of a low-dose intravenous magnesium load (0.1 mmol/kg body weight) was determined in 13 patients with chronic pancreatitis (10 due to alcoholism) and eight healthy controls. Percentage magnesium retention was greater in patients with chronic pancreatitis than controls (59.8+/-37.3% S.D. versus 22.0+/-38.2% S. D.: P=0.038), and 10 of 13 patients showed evidence of magnesium deficiency. Routine evaluation of magnesium status could allow appropriate supplementation and conceivably symptomatic improvement in patients with severe chronic pancreatitis.