| Budget Amount *help |
¥3,780,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
Intraductal Papillary Mucinous Neoplasms (IPMNs) express various mucins including MUC1, MUC2, MUC5AC, and MUC6. It has been reported that MUC1 immunoreactivity for a certain antibody is present in some invasive carcinomas associated with IPMNs. However, the expression profile of MUC1 immunoreactivity in these lesions may vary according to the clone of an anti-MUC1 antibody, because MUC1 exhibits various forms of glycosylation and thereby biding capacities of antibodies depend on the glycosylation form of MUC1. In this study, we evaluated the immunohistological expression profile of mucins in IPMNs and invasive carcinomas associated with IPMNs by using a variety of antibodies including three different clones for MUC1.
METHODs: Specimens of normal pancreatic ducts, IPMNs and invasive carcinomas were obtained from ten patients (non-pancreatic disease in two, IPMNs in six, intraductal papillary mucinous carcinoma with associated invasive tubular carcinoma in two) who underwent pancreatic re
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section at Osaka Medical College. Immunohistochemistry was performed by the avidin-biotin complex method with anti-MUC1 (clone Ma695, clone 1.10.F3, clone Ma552), anti-MUC2 (clone Ccp58), anti-MUC5AC (clone CLH2), and anti-MUC6 (clone CLH5) antibodies. Furthermore, anti-CDX1 (Orbigen Inc., PAB-10468), anti-CDX2 (Orbigen Inc., PAB-10469), anti-Sox (Santa Cruz, SC-17320), anti-PDX-1 (Santa Cruz, SC25403), anti-Notch (Santa Cruz, SC23304), anti-SHH (Santa Cruz, SC9024) antibodies were also used in additional experiments.
RESULTS: In normal intralobular ducts, MUC1 immunoreactivity for all three clones was confined to apical surfaces of ductal cells. In noninvasive lesions of IPMNs, MUC1 immunoreactivity was either confined to apical surfaces or entirely negative for all three clones. In invasive carcinomas associated with IPMNs, strong expression of MUC1 immunoreactivity in both nucleoplasm and cytoplasm was detected for the clone Ma695, while MUC1 immunostaining was equivocal or negative for clones 1.10E3 and Ma552. MUC5AC immunolabelling was abundantly positive in all lesions of IPMNs and invasive carcinomas, while MUC2 and MUC6 immunostaining was variable according to the histological phenotype of IPMNs.
CONCLUSION: Aberrant expression of MUC1 immunoreactivity for the clone Ma695, but not far other two clones, was clearly identified in invasive carcinomas associated with IPMNs. The glycosylation farm of MUC1 in invasive carcinomas associated with IPMNs may be different from that of MUC1 in non-invasive IPMNs and normal pancreatic ducts. lb clarify the mechanisms involved in differential mucin expression profiles, further study on expression profiles of CDX1, CDX2, Sox, PDX-1, Notch and sonic hedgehog is ongoing. Less
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