Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis

Chetty, Runjan; Serra, Stefano; Salahshor, Sima; Alsaad, Khaled O.; Shih, Warren; Blaszyk, Hagen; Woodgett, James R.; Tsao, Ming‐Sound

doi:10.1016/j.humpath.2005.11.002

Cited by 45 publications

(30 citation statements)

References 12 publications

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“…Allelic loss of the wild-type APC gene has been reported in an IPMN in a patient with familial adenomatous polyposis. Although the APC gene is only rarely, if ever, targeted in sporadic IPMNs, immunohistochemical analyses have demonstrated nuclear β-catenin immunolabeling and loss of APC expression in some sporadic IPMNs, indicating that the Wnt-signaling pathway is dysregulated in a proportion of IPMNs [80].…”

Section: Genes That Are More Selectively Altered In Ipmnsmentioning

confidence: 99%

Intraductal papillary mucinous neoplasm

Shi¹,

Hruban²

2012

Human Pathology

108

102

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Section: Genes That Are More Selectively Altered In Ipmnsmentioning

confidence: 99%

Intraductal papillary mucinous neoplasm

Shi¹,

Hruban²

2012

Human Pathology

108

102

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“…7 Briefly, formalin-fixed, paraffin-embedded tissue blocks containing normal or tumor tissue were cored and transferred to a recipient master block, using a Tissue Microarrayer (Beecher). The blocks were then processed and cut for staining.…”

Section: Tissue Array Construction and Immunohistochemical Analysismentioning

confidence: 99%

Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas

et al. 2008

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Esophageal squamous cell carcinoma is frequently associated with poor prognosis, as a result of high levels of lymph node metastasis. So far, very few genetic abnormalities have been associated with this disease, and its molecular etiology remains largely unknown. To assess whether the Wnt pathway contributes to esophageal squamous cell carcinoma, we characterized the expression and subcellular localization of the key Wnt signaling components in all 30 cases of esophageal squamous cell carcinomas analyzed. We found abnormal expression and/or localization in glycogen synthase kinase-3 a/b (34%), Axin2 (48%), a-catenin (31%), MYC (73%) and cyclin D1 in 46% of cases. Only 13% of tumors showed nuclear accumulation of b-catenin. By contrast, 60% showed nuclear expression of E-cadherin using an antibody that recognizes the cytoplasmic domain of E-cadherin. When the same tumors were stained with antibody raised against the extracellular domain of E-cadherin, the expression was lost. A direct correlation was found between nuclear E-cadherin and the increased nuclear cyclin D1, one of the AP-1 target genes in these tumors. By transfection experiments, the cytoplasmic portion of E-cadherin was found to activate the AP-1 transcription factor pathway and induced cyclin D1 promoter activity, but b-catenin/Tcf transcription activity was unaffected. Nuclear expression of E-cadherin was also detected in tumors other than squamous cell carcinoma, including pancreatic and colon cancers, albeit at lower frequency. Nuclear accumulation of a portion of E-cadherin in esophageal squamous cell carcinoma and the other types of tumors indicates that, in addition to the previously implicated tumor suppressor activity of E-cadherin, modified forms of this glycoprotein might also play a role in growth promotion. Keywords: Wnt signaling; esophageal squamous cell carcinomas; pancreatic cancer; colon cancer; E-cadherin Esophageal cancer is one of the deadliest but least studied forms of cancer and the sixth ranking cause of death from cancer in North America. It shows a varied geographical distribution and very poor survival rates. 1 Esophageal cancer accounts for 5% of all gastrointestinal cancers, and the overall number of new cases each year is steadily increasing. 2 Esophageal cancer can be divided into squamous cell carcinomas and adenocarcinomas. So far, very few genetic abnormalities have directly been linked to esophageal carcinogenesis. In this study, we sought to examine the expression and localization of the key components of the Wnt signaling pathway that have previously been shown to play important roles in colorectal, breast, stomach and prostate cancer. Wnt signaling regulates cell growth, motility and differentiation. Upon binding to their receptor, specific Wnt ligands trigger phosphorylation of LRP5/6 (low density lipoprotein) by glycogen synthase kinase-3 (GSK3a/b) and casein kinase-1 (CK1g), which distances Axin (Axin1 and Axin2) from the b-catenin destruction-complex. [3][4][5][6] As a result, the b-catenin is stabilized a...

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“…[16][17][18][19] IPMN is also associated with other extrapancreatic malignancies such as colorectal cancer. 20 Because of its variable malignant potential, the diagnostic and therapeutic challenge presented by IPMN is a singular one.…”

Section: Progress In the Diagnosis And Management Plan For This Pancrmentioning

confidence: 99%