TY - JOUR
T1 - Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays
AU - Fukushima, Noriyoshi
AU - Sato, Norihiro
AU - Prasad, Nijaguna
AU - Leach, Steven D.
AU - Hruban, Ralph H.
AU - Goggins, Michael
N1 - Funding Information:
This study was supported by the SPORE in Gastrointestinal Cancer (CA62924), the Lustgarten Foundation for Pancreatic Cancer Research, the Michael Rolfe Foundation and the Susan Gurney Fund for Pancreatic Cancer Research.
PY - 2004/12/2
Y1 - 2004/12/2
N2 - Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon neoplasms usually located in the body or tail of the pancreas and usually in females (> 90% of cases). Clinically, they are often misdiagnosed as non-neoplastic pseudocysts leading to failed opportunities for curative resection. To better understand the biology of MCNs and to identify markers of the disease, we performed global gene expression profiling of MCNs using oligonucleotide microarrays. Using laser capture microdissection applied to frozen sections, RNA was extracted from the neoplastic epithelium of MCNs, from the adjacent 'ovarian-type' stroma of MCNs, from histologically normal pancreatic ductal epithelium, from pancreatic acinar tissue and from fibrous stroma in pancreata affected by chronic pancreatitis. Each RNA sample was subjected to two rounds of linear amplification followed by hybridization with U133A gene chips (Affymetrix). The expression patterns of selected genes were confirmed by quantitative RT-PCR and by immunohistochemistry using tissue microarrays containing 19 resected MCNs. A total of 114 known genes were overexpressed in the neoplastic epithelium compared to normal pancreatic ductal epithelium (> 3-fold) including S100P, PSCA, c-myc, STK6/STK15, cathepsin E and pepsinogen C. Activation of the Notch pathway in the epithelial component of MCNs was evident by the demonstration of overexpression of Jagged1 and the downstream Notch pathway member Hes1. In the 'ovarian-type' stroma, several genes involved in estrogen metabolism were overexpressed including STAR and ESR1 genes. Some of the genes identified as overexpressed in these neoplasms may be useful as markers that can distinguish MCNs from non-neoplastic pancreatic cystic lesions.
AB - Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon neoplasms usually located in the body or tail of the pancreas and usually in females (> 90% of cases). Clinically, they are often misdiagnosed as non-neoplastic pseudocysts leading to failed opportunities for curative resection. To better understand the biology of MCNs and to identify markers of the disease, we performed global gene expression profiling of MCNs using oligonucleotide microarrays. Using laser capture microdissection applied to frozen sections, RNA was extracted from the neoplastic epithelium of MCNs, from the adjacent 'ovarian-type' stroma of MCNs, from histologically normal pancreatic ductal epithelium, from pancreatic acinar tissue and from fibrous stroma in pancreata affected by chronic pancreatitis. Each RNA sample was subjected to two rounds of linear amplification followed by hybridization with U133A gene chips (Affymetrix). The expression patterns of selected genes were confirmed by quantitative RT-PCR and by immunohistochemistry using tissue microarrays containing 19 resected MCNs. A total of 114 known genes were overexpressed in the neoplastic epithelium compared to normal pancreatic ductal epithelium (> 3-fold) including S100P, PSCA, c-myc, STK6/STK15, cathepsin E and pepsinogen C. Activation of the Notch pathway in the epithelial component of MCNs was evident by the demonstration of overexpression of Jagged1 and the downstream Notch pathway member Hes1. In the 'ovarian-type' stroma, several genes involved in estrogen metabolism were overexpressed including STAR and ESR1 genes. Some of the genes identified as overexpressed in these neoplasms may be useful as markers that can distinguish MCNs from non-neoplastic pancreatic cystic lesions.
KW - 'Ovarian-type' stroma
KW - Mucinous cystic neoplasm
KW - Oligonucleotide microarray
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U2 - 10.1038/sj.onc.1208117
DO - 10.1038/sj.onc.1208117
M3 - Article
C2 - 15489895
AN - SCOPUS:10944255781
SN - 0950-9232
VL - 23
SP - 9042
EP - 9051
JO - Oncogene
JF - Oncogene
IS - 56
ER -