EUS-FNA combined with Focused DNA Array (FDA) may be a good modality to predict future metastasis of pancreas carcinoma

Background: EUS has evolved from EUS imaging to EUS-guided FNA. EUS-guided FNA is now beyond cytology diagnosis and made it possible to analyze gene expression. Moreover, cDNA microarray technique allows us to test hundreds of genes simultaneously. The prediction of future metastasis is very important in treatment of pancreas carcinoma, especially before deciding surgery. The purpose of this study was to determine of the usefulness of Focused DNA Array (FDA) analysis using the pancreatic cancer tissue obtained by EUS-guided FNA for the prediction of metastasis.

Methods: Pancreatic cancer tissues were obtained from 26 patients by EUS-guided FNA. mRNA was harvested from each sample and cDNA was composed by reverse transcription polymerase chain reaction (RT-PCR). Expression of mRNA was evaluated using FDA which was restricted to 133 genes including genes which are known as important gens at late stage of tumor development such as growth factors and/or their receptors (EGFR, TGF beta 1, 2, 3), pro-angiogenic factors (VEGF), invasiveness factors (MMP (metalloproteinases) 1, 2, 3, 7, 9, 14, 16, ITG (Integrin) alfa 2, 3, 4, 5, Integrin beta 1, 3, 5). The expression of mRNA was measured as the relative value to house keeping gene. The patients were divided into two group who had metastasis or not and each gene expression was analyzed using Mann-Whitney U-test.

Results: 23/26 (88.5%) samples were suitable for analysis. There were 15/23 (65.2%) patients who had metastasis and there were 8/23 (34.8%) who had no metastasis at the time of biopsy. There was no significant difference seen between the group who had metastasis and no metastasis in following genes such as COX-2, CyclinD1, EGFR, ITGA2, ITGA3, ITGA4, ITGA5, ITGAV, ITGB1, ITGB3, MMP1, MMP14, MMP16, MMP2, MMP3, MMP7, MMP9, P53, PCNA, TGFB1, TGFB2, TGFB3, TGFBR3, TS, VEGF, VEGFC. However, there was significant difference seen in ITGB5 (p=0.037) which was known as subtype of integrin that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). The most important functions of surface integrin is their role in cell migration.

Conclusion: The gene analysis using EUS-guided FNA and FDA might be useful to predict future metastasis for patients with advanced pancreas carcinoma. ITG beta 5 may have an important role in metastasis of pancreas carcinoma.