1. ¹Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
2. ²Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
3. ³Department of Biostatistics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
4. ⁴Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
5. ⁵Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence: Dr LMS Resar, MD, Department of Medicine, The Johns Hopkins University School of Medicine, Ross Research Building, Room 1025, 720 Rutland Avenue, Baltimore, MD 21205, USA. E-mail: lresar@jhmi.edu; AC Hristov, MD, Department of Pathology, The Johns Hopkins University School of Medicine, Ross Research Building, Room 1025, 720 Rutland Avenue, Baltimore, MD 21205, USA. E-mail: acappie1@jhmi.edu

Received 30 June 2008; Revised 1 August 2008; Accepted 1 August 2008; Published online 29 August 2008.

Abstract

Pancreatic ductal adenocarcinoma is a highly aggressive, lethal human malignancy that continues to elude successful treatment. Although most patients present with metastatic disease, the molecular pathways that underlie tumor progression and metastases are poorly understood. The high mobility group A2 (HMGA2) protein is an architectural transcription factor that has recently been implicated in the development and progression of malignant tumors. Here, we examined HMGA2 gene expression in pancreatic ductal adenocarcinoma to determine if it could be a marker for more advanced disease. By real time quantitative RT-PCR, we showed a marked increase in HMGA2 mRNA in two of three cultured pancreatic ductal adenocarcinoma cell lines compared to normal pancreatic tissue. Using tissue microarrays generated from 124 pancreatic ductal adenocarcinoma cases, we also assessed HMGA2 protein levels by immunohistochemical analysis. We found that HMGA2 nuclear immunoreactivity correlates positively with lymph node metastases and high tumor grade. Our results support a role for HMGA2 in the progression of pancreatic ductal adenocarcinoma and suggest that it could be a useful biomarker and rational therapeutic target in more advanced disease.