S1815 Tissue Microarray Analysis in Pancreatic Adenocarcinoma

Abstract

The pathogenesis of pancreatic ductal adenocarcinoma involves the multi-stage development of molecular aberrations affecting signaling pathways that regulate cancer growth and progression. Tissue microarray analysis of pancreatic tumors allows simultaneous assessment of genetic disorders, which can lead to identification of biomarkers of poor prognosis. Aim: To characterize the gene expression of pancreatic adenocarcinoma compared to normal tissue from the same patient. Materials and methods. We investigated seven samples of T3 pancreatic adenocarcinoma obtained intraoperatively and compared them to normal pancreatic tissue from the same patients. RNAwas extracted and assessed qualitatively and quantitatively, followed by amplification of cDNA using reverse transcriptase, cRNA synthesis, and hybridization of microarray slides. For each sample 100 ng of total RNA was available. The overexpressed and underexpressed genes were classified by their known function in the cell. We selected six genes for analysis, some described previously in pancreatic pathology, and used RT-PCR for validation. Results: Five genes were overexpressed and 45 were underexpressed in the pancreatic adenocarcinoma samples. The overexpressed gene progastricsin PGC, with a role in extracellular matrix degradation, was validated by RT-PCR. Among the underexpressed genes we validated the protein kinase genes BCK1 and FABP4, with roles in desmoplastic reaction CD36, which modulates insulin secretion; UNC13A, involved in formation of presynaptic vesicles and probably nervous hyperexcitability; and RNH1, with a role in the inhibition of angiogenesis. The geneMUC12, with a role in epithelial growth, was underexpressed in microarray analysis, but overexpressed on validation. Conclusion: Microarray tissue analysis of pancreatic adenocarcinoma showed more underexpressed than overexpressed genes. After validation , the overexpressed gene progastricsin PGC was shown to be one factor responsible for tumor progression and metastasis formation. The possible role in pancreatic cancer of loss of MUC12, known to be an early event of carcinogenesis in colorectal cancer, should be further clarified.