Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.

PURPOSE: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. EXPERIMENTAL DESIGN: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. RESULTS: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARalpha, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. CONCLUSIONS: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

Focused image-guided parathyroidectomy in the current management of primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) in childhood and adolescence has been considered a different disease to that seen in adults, with predominantly familial aetiology mandating open exploration to exclude parathyroid hyperplasia in contrast to the adoption of focused image-guided parathyroidectomy (FP) in adults. STUDY DESIGN: A retrospective cohort study in a tertiary referral hospital setting of all children and adolescents (<18 years) undergoing parathyroid surgery for PHPT. Data were obtained from a dedicated endocrine surgery database and hospital medical records. RESULTS: Over the 35-year study period (1980-2014), there were 31 patients who underwent parathyroidectomy for PHPT. 3 patients were from known multiple endocrine neoplasia type 1 syndrome (MEN1) families, 3 had an isolated family history of PHPT and 25 were sporadic. In the sporadic group, 24 (96%) presented with symptomatic hypercalcaemia, affecting the gastrointestinal, musculoskeletal, genitourinary or neuropsychiatric systems. In the 25 patients with sporadic PHPT, nine (36%) had FP with a single adenoma removed with a 100% initial cure rate. Sixteen patients (64%) in the sporadic group had an open exploration: 14 had single gland disease while 2 patients required a second procedure to achieve a final cure rate of 100%. Of the three patients with MEN1, one was cured, one has persistent hyperparathyroidism after FP and the third has permanent hypoparathyroidism after open exploration. CONCLUSIONS: The majority of children and adolescents with PHPT have symptomatic disease due to a single adenoma. They can therefore be managed in a similar fashion to their adult counterparts with preoperative localisation studies aiming to permit FP in a day case setting.