Different pancreatic cancer genomic risk prediction models derived from microdissected and non-microdissected paraffin-embedded tissue.

4622 Background: Microarray studies of genomic risk models for patients with various cancers often use fresh frozen tissue containing both tumor and non-tumor tissue. To assess the effect of using isolated tumor tissue for microarray analysis versus the entire unprocessed specimen, we compared gene expression profiles associated with long-term and short term-survival derived from microdissected and non-microdissected FFPE pancreatic cancer specimens.,We selected pathologically confirmed pancreatic ductal adenocarcinoma from archival FFPE specimens from a single center. Among 20 specimens, 14 were from long-term (>36 mos.) and 6 from short-term (< 5 mos.) survivors. Multiple slide sections taken from each paraffin block were either microdissected to isolate tumor cells or isolated en bloc. Non-microdissected samples contained roughly 20% tumor cells, as is typical for this desmoplastic disease. Following isolation, RNA was amplified, labeled, and hybridized to Affymetrix U133 Plus 2.0 GeneChips. Differentially expressed gene lists were determined between long (>645 days) and short survivors (<204 days) by T-Test and hierarchical clustering.,Between the groups of all microdissected and all non-microdissected specimens there were 8531 differentially expressed genes at p<0.05. In the microdissected samples, gene clusters created with supervised analyses based on outcome identified 359 differentially expressed genes between the long-term and the short-term survivor groups (p=0.005). Interestingly, 219 differentially expressed genes were also identified in the non-microdissected samples (p=0.005). However, Venn diagrams showed only 3 genes in common genes between the two groups. Diagnostic gene sets from microdissected samples failed to properly classify the non-microdissected samples and vice versa.,Gene profiles generated from microdissected and non-microdissected samples of the same tumors are very dissimilar, but both contain prognostic information. Thus, non-microdissected samples containing a minority percentage of tumor cells do not give gene profiles characteristic of cancer, but most likely of pathologic stromal-tumor interaction. [Table: see text].