Ongoing projects

 

Completed projects

 

Methods

 

Overall research interests

THE PROBLEM
According to recent statistics from the Association of Population-Based Cancer Registries in Germany the estimated number of new cases of ductal adenocarcinoma of the pancreas (PDAC) was 12,650 in 2002. As with other statistics world wide the mortality of this cancer type was confirmed in this recent statistic to be the highest of any cancer type in Germany which is also indicated by its very low 5-year survival rate (0.5%-5%)(1).

The Molecular GI-Oncology Laboratory at the Ruhr-University of Bochum is dedicated to the molecular analysis of human pancreatic ductal adenocarcinoma (PDAC). PDAC arises as the result of a series of genetic changes. This successive accumulation of changes drive tumor progression initiated in normal (ductal?) pancreatic cells by giving rise to the so called early lesions (also called pancreatic intraepithelial neoplasia, PanIN-1A & B) followed by the more advanced PanIN-2 and -3 lesions and ultimately leading to the formation of metastatic cancer cells. PanINs are subclassified according to their grade of dysplasia into PanIN-1A, PanIN-1B (no dysplasia), PanIN-2 (low to intermediate grade dysplasia) and PanIN-3 (high grade dysplasia)(see also classification of duct lesions of the pancreas at JHU). PDAC, for which early symptoms are rare and uncharacteristic, are commonly diagnosed in advanced stage of the disease. To date, the best imaging technologies to detect  PDAC are endoscopic ultrasound (EUS), spiral computer tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP). Unfortunately, the resolution of these technologies for detecting neoplastic lesions within the pancreas is in the range of 3-10 mm under optimal conditions and it remains to be proven within clinical trials, whether screening with these technologies is able to detect pancreatic neoplasia at a curable stage. The serum concentration of tumor markers such as CA19-9 is increased in pancreatic cancer but so far they all lack sensitivity and tumor specificity. Thus, new approaches are urgently needed to increase the diagnostic sensitivity towards the detection of very small, early stage PDAC and its precursor lesions PanIN-3 or the carcinoma in situ (CIS) stage of the disease and to develop effective therapeutic (including chemoprevention) strategies for PDAC treatment. With other words, a detailed knowledge of the critical biological changes responsible for pancreatic tumorigenesis is essential for the development of early diagnostic and preventive strategies. Therefore our lab has applied in the past together with several collaborators methods to establish loss of heterozygosity frequencies (LOH), gene expression and miRNA profiles from macro- and/or microdissected PDACs and/or PanINs aiming at the identification of such key changes. This knowledge is currently been used among others to develop molecular imaging tools for early diagnosis of PDAC and to explore aberrantly expressed miRNAs as therapeutic targets.

In addition to the PDAC cancer risk of the normal population a number of syndromes with an increased incidence of PDAC have been described in more details in recent years, including familial pancreatic carcinoma (FPC), familial atypical multiple mole melanoma (FAMMM) and Peutz-Jeghers syndrome (PJS) (2). Therefore, our group is engaged in collaboration with Groups from the University Hospital Gießen and Marburg in building a national familial pancreatic carcinoma registry (FaPaCa ) for the study of PDAC arising in a familial setting with the long term goal to improve clinical care for these families.

REFERENCES
1.   G. Schneider, J. T. Siveke, F. Eckel, R. M. Schmid, Gastroenterology 128, 1606 (2005).
2.   S. A. Hahn, D. K. Bartsch, Clin Lab Med 25, 117 (2005).