Apc Expression in Normal Human Tissues

Midgley, Carol A.; White, Susan; Howitt, Rachel; Save, Vicki; Dunlop, Malcolm; Hall, Peter A.; Lane, David P.; Wyllie, Andrew H.; Bubb, Vivien J.

doi:10.1002/(sici)1096-9896(199704)181:4<426::aid-path768>3.0.co;2-t

Cited by 90 publications

(40 citation statements)

References 38 publications

(40 reference statements)

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“…Moreover, and catenin, as well as E-cadherin, are known to be associated with the APC tumour suppressor gene; this association is stronger and more specific than similar associations in any other type of sporadic epithelial tumour. 24 Most of the mutations in APC result in truncated APC protein, which can complex with but not degrade catenin. The net result of APC mutation is an increase in cytoplasmic catenin, which may then trigger a cascade of events resulting in the initiation of adenomas.…”

Section: Discussionmentioning

confidence: 99%

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Ropponen

Eskelinen

Lipponen

et al. 1999

Journal of Clinical Pathology

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Aims-To investigate catenin expression in surgically resected human colorectal cancers to evaluate its prognostic value during long term follow up. Methods-Immunohistochemistry was used to compare the expression of catenin with conventional prognostic factors in 187 colorectal cancer patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the intensity of expression of catenin and its distribution in cancer cells is correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. Results-Uniform membranous catenin staining localised to the intercellular borders was observed in 46% of the tumours; 55% of all tumours had either heterogeneous or negative catenin expression, and staining intensity was either negative or weak in 42% of the tumours. The cancer related and recurrence-free survival rates were lower among patients with a weak catenin intensity in tumour epithelium (p < 0.001), a low fraction of positive tumour cells (p < 0.001), and an additional cytoplasmic accumulation of catenin (p < 0.001). In multivariate analysis, the intensity of catenin expression in tumour epithelium predicted cancer related survival independently; catenin localisation in tumour epithelium was an independent prognostic factor of recurrence-free survival in the group as a whole and in the T1-3N0M0 tumour subgroup. Conclusions-A low proportion of positive carcinoma cells, additional cytoplasmic accumulation of catenin, and reduced expression intensity in tumour epithelium predict a poor survival rate. The results suggest that catenin has prognostic significance in colorectal cancer. (J Clin Pathol 1999;52:10-16)

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Section: Discussionmentioning

confidence: 99%

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Ropponen

Eskelinen

Lipponen

et al. 1999

Journal of Clinical Pathology

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“…3). According to this 'just-right signalling' model, the signalling function of APC must be impaired to a specific degree to allow sufficient accumulation of www.nature.com/reviews/cancer R E V I E W S level of expression with maturation, whereas it is virtually absent in the crypt region where cells are actively dividing 104,105 . This pattern of expression is in agreement with the role of β-catenin signalling in maintaining stem-cell properties and controlling differentiation in the intestine 106 .…”

Section: Downstream Targets Of Apc/β-catenin Signallingmentioning

confidence: 99%

APC, Signal transduction and genetic instability in colorectal cancer

2001

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Colorectal cancer arises through a gradual series of histological changes, each of which is accompanied by a specific genetic alteration. In general, an intestinal cell needs to comply with two essential requirements to develop into a cancer: it must acquire selective advantage to allow for the initial clonal expansion, and genetic instability to allow for multiple hits in other genes that are responsible for tumour progression and malignant transformation. Inactivation of APC--the gene responsible for most cases of colorectal cancer--might fulfil both requirements.

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“…In support of this, APC mutations have been observed in tumors of the esophagus, stomach, and pancreas (1). In support of this, APC mutations have been observed in tumors of the esophagus, stomach, and pancreas (1).…”

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confidence: 54%

“…Most APC mutations result in a truncated protein with a detectable loss in the C-terminal region (1,2). Recently, novel antibodies to this C-terminal region have been described that can be used on formalin-fixed, paraffinembedded tissue (1).…”

mentioning

confidence: 99%