Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas - PubMed (original) (raw)

Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas

Benoit Terris et al. Am J Pathol. 2002 May.

Abstract

The molecular pathology of precursor lesions leading to invasive pancreatic ductal adenocarcinomas remains relatively unknown. We have applied cDNA microarray analysis to characterize gene expression profiles in a series of intraductal papillary-mucinous tumors (IPMTs) of the pancreas, which represents one of the alternative routes of intraepithelial progression to full malignancy in the pancreatic duct system. Using a cDNA microarray containing 4992 human genes, we screened a total of 13 IPMTs including nine noninvasive and four invasive cases. Expression change in more than half of the tumors was observed for 120 genes, ie, 62 up-regulated and 58 down-regulated genes. Some of the up-regulated genes in this study have been previously described in classical pancreatic carcinomas such as lipocalin 2, galectin 3, claudin 4, and cathepsin E. The most highly up-regulated genes in IPMTs corresponded to three members of the trefoil factor family (TFF1, TFF2, and TFF3). Immunohistochemistry performed on five genes found to be differentially expressed at the RNA level (TFF1, TFF2, TFF3, lipocalin 2, and galectin 3) showed a good concordance between transcript level and protein abundance, except for TFF2. Hierarchical clustering organized the cases according to the dysplastic and invasive phenotype of theIPMTs. This analysis has permitted us to implicate several genes (caveolin 1, glypican 1, growth arrest-specific 6 protein, cysteine-rich angiogenic inducer 61) in tumor progression. The observation that several genes are differentially expressed both in IPMTs and pancreatic carcinomas suggests that they may be involved at an early stage of pancreatic carcinogenesis.

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Figures

Figure 1.

Figure 1.

Variation in expression of 2906 genes in 13 IPMTs. Each row represents individual genes and each column an experimental sample. The ratio of the abundance of transcripts of each gene to its median abundance across all tumors is represented by the color: green (transcript levels below median), black (equal to the median), red (greater than the median), and gray (technically inadequate or missing data). Color intensity reflects the magnitude of the ratio relative to the median for each set of samples. A: Overall groupings of genes and samples. B: The dendrogram of samples showed two main branches with all of the invasive cases (colored in pink) occupying the same branch. Two separate clusters were identified containing genes differentially expressed between invasive and noninvasive tumors.

Figure 2.

Figure 2.

Immunohistochemical staining of IPMT. Intense homogeneous positive staining was seen in neoplastic epithelial cells with TFF1 (A), TFF3 (C), and galectin 3 (D). Immunoreactivity for TFF2 was typically heterogeneous and only moderately intense (B).

Comment in

References

    1. Loftus EV, Jr, Olivares-Pakzad BA, Batts KP, Adkins MC, Stephens DH, Sarr MG, DiMagno EP: Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic. Gastroenterology 1996, 110:1909-1918 - PubMed
    1. Kloppel G: Clinicopathologic view of intraductal papillary-mucinous tumor of the pancreas. Hepatogastroenterology 1998, 45:1981-1985 - PubMed
    1. Terris B, Ponsot P, Paye F, Hammel P, Sauvanet A, Molas G, Bernades P, Belghiti J, Ruszniewski P, Flejou JF: Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 2000, 24:1372-1377 - PubMed
    1. Luttges J, Schlehe B, Menke MA, Vogel I, Henne-Bruns D, Kloppel G: The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic ductal epithelium. Cancer 1999, 85:1703-1710 - PubMed
    1. Heinmoller E, Dietmaier W, Zirngibl H, Heinmoller P, Scaringe W, Jauch KW, Hofstadter F, Ruschoff J: Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma. Am J Pathol 2000, 157:83-92 - PMC - PubMed

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