Nuclear Translocation of β-Catenin Protein but Absence of β-Catenin and APC Mutation in Gastrointestinal Carcinoid Tumor

Su, Min-Cheng; Chen, Chun-Chin; Hu, Rey‐Heng; Wang, Ting-Huang; Kao, Hsin-Lien; Jeng, Yung‐Ming; Yuan, Ray-Hwang

doi:10.1245/s10434-006-9072-2

Cited by 25 publications

(20 citation statements)

References 32 publications

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“…Areas with stronger protein expression were evaluated in tumours with zonal staining pattern. Su et al 2006). PCR was performed in a final volume of 50 ml, with 25 pmol of each primer, 0.8 mM total dNTPs, 1.5 mM MgCl 2 and 1.25 units AmpliTaq Gold (Applied Biosystem, Foster City, CA, USA).…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…www.endocrinology-journals.org different series (Semba et al 2000, Fujimori et al 2001, Su et al 2006. Nonetheless, abnormal b-catenin expression was frequently observed, often with concurrent loss of membranous E-cadherin expression, and usually associated with malignant features (Fujimori et al 2001).…”

Section: S Pizzi Et Al: Wnt Pathway and Endocrine Tumoursmentioning

confidence: 99%

“…In digestive neuroendocrine tumours, abnormal b-catenin expression was frequently found, though mutation of b-catenin exon 3 was reported by some and not by others, most often in the absence of APC mutations (Gerdes et al 1999, Semba et al 2000, Fujimori et al 2001, Barshack et al 2002, Li et al 2002, Hervieu et al 2006, Su et al 2006. Additionally, APC promoter methylation was reported in digestive endocrine tumours (House et al 2003, Arnold et al 2004a.…”

Section: Introductionmentioning

confidence: 99%

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Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of -catenin and chromosomal instability

Pizzi¹,

Azzoni²,

Tamburini³

et al. 2008

Endocrine Related Cancer

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The role of Wnt pathway in digestive endocrine tumours is debated. The aim of this work is to investigate key players in Wnt pathway by a multimodal approach. Sixty cases (49 well-differentiated and 11 poorly differentiated) were investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin promoters, the loss of heterozygosity (LOH) at APC locus and b-catenin and E-cadherin expression by immunohistochemistry. Tumours showing altered b-catenin localization were tested for b-catenin and APC mutations. APC promoter methylation was restricted to gastroduodenal tumours (21 out of 59, 36%), prevalent in poorly differentiated carcinomas (PZ0.042) and correlating with aggressive features (high histology grade, P!0.02; tumour death, PZ0.026; high fractional allelic loss, PZ0.002, in turn correlating with short survival, PZ0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10 gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas (PZ0.002) and correlating with histology grade (PZ0.012). b-catenin abnormal expression was found in 41 out of 54 cases (76%), with nuclear staining correlating with APC alteration (PZ0.047) and short survival (PZ0.006). APC, but not b-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in the midgut. E-cadherin promoter methylation was rarely detected (2 out of 52 cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as represented by abnormal b-catenin localization, are common events in digestive endocrine tumours, but only nuclear expression correlates with tumour aggressiveness. Though with different alteration mechanisms according to anatomical site, APC plays a major role in Wnt pathway activation and in determining the high chromosomal instability observed in aggressive endocrine carcinomas.

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Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Section: S Pizzi Et Al: Wnt Pathway and Endocrine Tumoursmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of -catenin and chromosomal instability

Pizzi¹,

Azzoni²,

Tamburini³

et al. 2008

Endocrine Related Cancer

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“…There are only two reports investigating APC mutation in PanNET; one study examined a clinical sample with no mutation and the other examined two PanNET cell lines with APC mutations [22,26]. However, there are seven reports that examined β-catenin abnormality, and only six (3.1%) of 191 reported cases have either nuclear accumulation of β-catenin or β-catenin mutations [27][28][29][30][31][32][33]. PTEN and STK11 suppress the activation of the mTOR signaling pathway, and loss-of-function mutations for these genes result in the activation of this signal [34,35].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Cancer-related Genes Associated with Grading of Well Differentiated Pancreatic Neuroendocrine Neoplasms

Yokota¹,

Fukasawa²,

Takano³

et al. 2017

Pancreat Disord Ther

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Objectives: Although recent advances in next-generation sequencing (NGS) have revealed some genetic alterations in various tumors, including pancreatic neuroendocrine tumors (PanNETs), their clinical significance is not fully understood. To investigate the clinical significance of gene alteration in PanNETs, we performed genetic analysis of well differentiated PanNETs using NGS.Methods: Twenty-nine resected primary PanNET tissue samples and three samples of metastatic liver tissues, obtained from 29 PanNET patients, were analyzed. DNA was extracted from laser-captured formalin-fixed paraffinembedded tissues, and 50 cancer-associated genes, including approximately 2,800 hotspots, were amplified by multiplex PCR. Amplified libraries were sequenced using NGS, and the results were analyzed in conjunction with respective clinicopathological features. Results:Among 50 investigated genes, somatic mutations were observed in four of 29 PanNET cases. We identified APC mutations in three cases, PTEN in two, and VHL and STK11 in one. The identified mutations were observed only in NET G2 tumors. All liver metastases contained at least one mutation, such as PTEN or TP53, which was not observed in the primary tumor. Conclusion:The cancer-related gene mutations observed in PanNETs were associated with G2 grade tumors. The mutations were more frequent in PanNET liver metastasis than in the primary tumors. Our analysis of liver metastasis cases suggested that cancer-related gene mutations might raise the tumor grade and promote liver metastasis. Further studies of associations between genetic alterations and clinicopathological features should help in the cancer diagnosis and prediction of therapeutic effects of molecular-target drugs.

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“…Da immunhistochemisch die nukleäre Positivität für -Catenin bei 79% der Fälle lag [41], muss angenommen werden, dass möglicher-weise bislang nicht bekannte Mechanismen für die Akkumulation dieses Proteins im Kern verantwortlich sind. In einer späteren Studie lag die nukleäre Translokation von -Catenin jedoch nur bei 30%, und Exon-3-Mutationen konnten nicht nachgewiesen werden [42]. Weitere für Adenokarzinome charakteristische Onkogene wie HER2 oder k-RAS scheinen für die Tumorgenese von NET nicht von Bedeutung zu sein [43].…”

Section: Mutationsanalyseunclassified

Gastroenteropankreatische neuroendokrine Tumoren: Molekulargenetische Charakteristika

et al. 2010

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Neuroendokrine Tumoren des gastroenteropankreatischen Systems (GEP-NET) sind charakterisiert durch die Expression neuroendokriner Marker sowie die Synthese, Speicherung und Sekretion von Peptidhormonen und/ oder biogenen Aminen. Es handelt sich um mehr als 50 unterschiedliche Tumorentitäten mit klinisch sehr unterschiedlichem Verlauf. Sie können sporadisch oder familiär auftreten. Die hohe biologische und klinische Vielfalt äußert sich in unterschiedlichen genetischen Profilen auf DNA- und mRNA-Ebene, welche wie folgt zusammengefasst werden können: 1. NET unterscheiden sich genetisch von den häufigen nichtneuroendokrinen Karzinomen des Verdauungstraktes. 2. Die klinisch-pathologische Heterogenität der GEP-NET spiegelt sich auch auf genetischer Ebene wider. 3. Bei pankreatischen NET finden sich deutliche genetische Unterschiede zwischen Insulinomen und anderen Entitäten. 4. Die Tumorprogression geht bei pankreatischen NET mit einer Zunahme von genetischen Veränderungen einher. 5. Pankreatische NET unterscheiden sich genetisch von gastrointestinalen NET. 6. Sporadische GEP-NET unterscheiden sich genetisch von hereditären (familiären) GEP-NET.

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Nuclear Translocation of β-Catenin Protein but Absence of β-Catenin and APC Mutation in Gastrointestinal Carcinoid Tumor

Cited by 25 publications

References 32 publications

Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of -catenin and chromosomal instability

Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of -catenin and chromosomal instability

Alterations in Cancer-related Genes Associated with Grading of Well Differentiated Pancreatic Neuroendocrine Neoplasms

Gastroenteropankreatische neuroendokrine Tumoren: Molekulargenetische Charakteristika

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