β-catenin expression in relation to genetic instability and prognosis in colorectal cancer

Mårtensson, Ann; Öberg, Åke; Jung, Andreas; Cederquist, Kristina; Stenling, Roger; Palmqvist, Richard

doi:10.3892/or.17.2.447

Cited by 42 publications

(46 citation statements)

References 31 publications

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“…Nuclear accumulation of β-catenin is believed to be a crucial step in the carcinogenesis of CRC (1-3). In fact, ≤80% of colorectal tumors exhibit nuclear accumulation of β-catenin (7)(8)(9). Furthermore, in ≤90% of all CRCs, a mutation in a key regulator of the Wnt signaling pathway, such as β-catenin, can be detected (10).…”

Section: Discussionmentioning

confidence: 99%

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor

et al. 2015

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Abstract. The wingless-type mouse mammary tumor virus integration site family (Wnt) pathway plays a major role in the carcinogenesis of colorectal cancer (CRC). Its most important effector, the nuclear β-catenin, influences not only transcription but also the proliferation and dedifferentiation of the colonic mucosa. This induces an epithelial-mesenchymal transition which ultimately can lead to the development of cancer and the formation of metastases. However, little is known about the exact interaction and context-sensitive expression of Wnt-pathway effectors in the primary tumor and corresponding metastasis. Therefore, this study assessed the expression of the three most important effectors of the Wnt pathway, β-catenin, adenomatous polyposis coli (APC) and Wnt-1, in the primary tumor and corresponding metastasis of patients with CRC. Immunohistochemical staining of β-catenin, APC and Wnt-1 was performed in paraffin-embedded tissue samples of the primary tumor, and the corresponding hepatic and nodal metastasis samples from 24 patients with metastatic CRC. Isotype antibodies were used as negative controls. The results were visualized using the ABC-method. Analysis of the primary tumor comprised of a separate evaluation of the central tumor area as well as the invasion front. There was a significant overexpression of nuclear β-catenin at the tumor invasion front (P<0.001). Compared to normal colonic mucosa, expression of cytoplasmic β-catenin was significantly higher in the primary tumor (P<0.001) as well as all the corresponding hepatic and lymphatic metastases (hepatic metastases, P=0.001; nodal metastases, P=0.017). By contrast, APC expression was significantly lower in all analyzed tumor compartments compared with normal colonic mucosa (primary tumor, P=0.022; hepatic metastases, P=0.006; nodal metastases, P=0.012). Finally, Wnt-1 protein expression was significantly lower in liver metastases but not in the primary tumor or lymphatic metastases compared with normal colonic mucosa (P=0.003). The present study demonstrates that the major Wnt-effector proteins, β-catenin, APC and Wnt-1, are heterogeneously expressed in the primary tumor and corresponding hepatic as well as nodal metastases of patients with CRC. This context-sensitive diverse expression of Wnt-effector proteins may be important for future individualized targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor

et al. 2015

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“…Another evidence indicates that high levels of WNT1 and β -catenin expression are associated with advanced, metastatic, hormone-refractory prostate carcinoma, in which they can serve as markers of disease progression (Chen et al 2004). Overexpression of β -catenin appears to have pathologic and prognostic significance in colorectal cancer and hepatocellular carcinoma (Wong et al 2001;Martensson et al 2007). An interesting study shows that BAGE or GAGE expression is related significantly to poor prognosis in esophageal carcinoma, whereas the expression of MAGE genes (in the absence of BAGE and GAGE expression) is related significantly to good prognosis (Zambon et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profile of Salivary Adenoid Cystic Carcinoma Associated with Perineural Invasion

Chen

Zhang

Shao

et al. 2007

Tohoku J. Exp. Med.

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Adenoid cystic carcinoma (ACC) is a common salivary gland malignancy characterized by slow but progressive clinical course, proclivity for hematogenous spread and perineural invasion (PNI) that exhibits inherent resistance to complete surgical resection, systemic chemotherapy and conventional radiotherapy. The molecular alterations that underlie its PNI are poorly characterized. We report the combined use of laser capture microdissection (LCM) and high-throughput cDNA microarray to monitor in vivo gene expression profile of salivary ACC and to correlate the profile with PNI. Consecutive section staining with hematoxylin & eosin was applied to 15 cancerous tissues, among which 6 were judged as PNI. Pure cancer cells adjacent to the nerve tracts from 6 cancerous tissues judged as PNI were laser captured, and pure cancer cells from the same 6 tumors distant from the nerve tracts were also procured. Total RNA was extracted, amplified and subjected to cDNA microarray-based expression analysis. The patterns of gene expression were verified by quantitative real-time PCR and immunohistochemistry. As to the result of 6 arrays, a total of 53 genes were identified as being 2-fold or more differentially expressed in PNI cancer cell group as compared to non-PNI cancer cell control. Out of the 53 genes found consistently differentially expressed, 38 were up-regulated and 15 down-regulated. The combined use of LCM and cDNA microarray analysis provides a powerful new approach to monitor the in vivo molecular events of PNI in salivary ACC. These identified novel genes deserve further investigations to elucidate their clinicopathological significance.carcinoma, adenoid cystic; perineural invasion; microarray; laser capture microdissection; gene expression

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“…[27]noticed that the expression of nuclear β-catenin increased during the development of carcinoma. There is also evidence that carcinoma in situ CRCs are frequently associated with high nuclear β-catenin expression [28].…”

Section: Materials and Methods:-mentioning

confidence: 99%

Clinicopathological Significance of Fascin1 and Β-Catenin Expression in Colorectal Adenocarcinoma; An Immunohistochemical Study"

Atwa¹,

Abdelbary.²,

Baiomy³

et al. 2017

IJAR

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β-catenin expression in relation to genetic instability and prognosis in colorectal cancer

Cited by 42 publications

References 31 publications

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor

Gene Expression Profile of Salivary Adenoid Cystic Carcinoma Associated with Perineural Invasion

Clinicopathological Significance of Fascin1 and Β-Catenin Expression in Colorectal Adenocarcinoma; An Immunohistochemical Study"

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