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Erschienen in: Annals of Surgical Oncology 6/2011

01.06.2011 | Colorectal Cancer

Prognostic Value of Nuclear β-catenin Overexpression at Invasive Front in Colorectal Cancer for Synchronous Liver Metastasis

verfasst von: Lin Wang, MD, Hongxia Cheng, MD, Ying Liu, MD, Lei Wang, MD, Wenbin Yu, MD, Guangyong Zhang, MD, Bo Chen, MD, Zhiyong Yu, MD, Sanyuan Hu, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 6/2011

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Abstract

Background

β-catenin plays an important role in colorectal tumorigenesis. Relatively little is known about the relationship between β-catenin overexpression and liver metastasis. The purpose of this study was to investigate whether nuclear β-catenin overexpression in colorectal cancer is associated with synchronous liver metastasis.

Methods

The β-catenin expression in tumor tissue from 486 patients with colorectal cancer was examined by immunohistochemistry. The relationship between nuclear β-catenin expression in colorectal cancers and liver metastatic lesions and other clinicopathological characteristics was analyzed. Univariate analysis and logistic multivariate regression analysis were adopted to discriminate risk factors of liver metastasis.

Results

Nuclear β-catenin overexpression at the invasive front of the primary tumor in patients with liver metastasis is more evident than that in patients without liver metastasis (71.5% vs. 29.3%; P < 0.001). Nuclear β-catenin expression in primary tumors had a positive correlation with that in the matched metastatic lesions (r = 0.499, P < 0.001). Univariate and multivariate analyses indicated that overexpression of nuclear β-catenin at the invasive front in colorectal cancer correlated with liver metastasis.

Conclusions

Overexpression of nuclear β-catenin at the invasive front in colorectal cancer is strongly associated with liver metastasis and may be a promising predictor of liver metastasis.
Literatur
1.
Zurück zum Zitat Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2004;54:8–29.PubMedCrossRef Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2004;54:8–29.PubMedCrossRef
2.
Zurück zum Zitat Laffer UT, Metzger U. Intraportal chemotherapy for colorectal hepatic metastases. World J Surg. 1995;19:246–51.PubMedCrossRef Laffer UT, Metzger U. Intraportal chemotherapy for colorectal hepatic metastases. World J Surg. 1995;19:246–51.PubMedCrossRef
3.
Zurück zum Zitat Sasaki A, Iwashita Y, Shibata K, Matsumoto T, Ohta M, Inomata M, et al. Risk factors for early extrahepatic metastasis in patients with liver metastasis from colorectal carcinoma. Hepatogastroenterology. 2005;52:1840–4.PubMed Sasaki A, Iwashita Y, Shibata K, Matsumoto T, Ohta M, Inomata M, et al. Risk factors for early extrahepatic metastasis in patients with liver metastasis from colorectal carcinoma. Hepatogastroenterology. 2005;52:1840–4.PubMed
4.
Zurück zum Zitat Barozzi C, Ravaioli M, D’Errico A, Grazi GL, Poggioli G, Cavrini G, et al. Relevance of biologic markers in colorectal carcinoma: a comparative study of a broad panel. Cancer. 2002;94:647–57.PubMedCrossRef Barozzi C, Ravaioli M, D’Errico A, Grazi GL, Poggioli G, Cavrini G, et al. Relevance of biologic markers in colorectal carcinoma: a comparative study of a broad panel. Cancer. 2002;94:647–57.PubMedCrossRef
5.
Zurück zum Zitat Kaio E, Tanaka S, Kitadai Y, Sumii M, Yoshihara M, Haruma K, et al. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology. 2003;64:61–73.PubMedCrossRef Kaio E, Tanaka S, Kitadai Y, Sumii M, Yoshihara M, Haruma K, et al. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology. 2003;64:61–73.PubMedCrossRef
6.
Zurück zum Zitat Iwaya K, Oikawa K, Semba S, Tsuchiya B, Mukai Y, Otsubo T, et al. Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinoma. Cancer Sci. 2007;98:992–9.PubMedCrossRef Iwaya K, Oikawa K, Semba S, Tsuchiya B, Mukai Y, Otsubo T, et al. Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinoma. Cancer Sci. 2007;98:992–9.PubMedCrossRef
7.
Zurück zum Zitat Chen Z, Li M, Yuan Y, Wang Q, Yan L, Gu J. Cancer/testis antigens and clinical risk factors for liver metastasis of colorectal cancer: a predictive panel. Dis Colon Rectum. 2010;53:31–8.PubMedCrossRef Chen Z, Li M, Yuan Y, Wang Q, Yan L, Gu J. Cancer/testis antigens and clinical risk factors for liver metastasis of colorectal cancer: a predictive panel. Dis Colon Rectum. 2010;53:31–8.PubMedCrossRef
8.
Zurück zum Zitat Talbot IC, Ritchie S, Leighton MH, Hughes AO, Bussey HJ, Morson BC. The clinical significance of invasion of veins by rectal cancer. Br J Surg. 1980;67:439–42.PubMedCrossRef Talbot IC, Ritchie S, Leighton MH, Hughes AO, Bussey HJ, Morson BC. The clinical significance of invasion of veins by rectal cancer. Br J Surg. 1980;67:439–42.PubMedCrossRef
9.
Zurück zum Zitat Yamazoe Y, Maetani S, Onodera H, Nishikawa T, Tobe T. Histopathological prediction of liver metastasis after curative resection of colorectal cancer. Surg Oncol. 1992;1:237–44.PubMedCrossRef Yamazoe Y, Maetani S, Onodera H, Nishikawa T, Tobe T. Histopathological prediction of liver metastasis after curative resection of colorectal cancer. Surg Oncol. 1992;1:237–44.PubMedCrossRef
10.
Zurück zum Zitat Shiiki S, Fuchimoto S, Iwagaki H (1991) Clinicopathological study on colorectal cancer with synchronous liver metastasis. J Jpn Soc Coloproctol. l44: 1107–12. Shiiki S, Fuchimoto S, Iwagaki H (1991) Clinicopathological study on colorectal cancer with synchronous liver metastasis. J Jpn Soc Coloproctol. l44: 1107–12.
11.
Zurück zum Zitat Adachi Y, Inomata M, Kakisako K, Sato K, Shiraishi N, Kitano S. Histopathologic characteristics of colorectal cancer with liver metastasis. Dis Colon Rectum. 1999;42:1053–6.PubMedCrossRef Adachi Y, Inomata M, Kakisako K, Sato K, Shiraishi N, Kitano S. Histopathologic characteristics of colorectal cancer with liver metastasis. Dis Colon Rectum. 1999;42:1053–6.PubMedCrossRef
12.
Zurück zum Zitat De Jong KP, Stellema R, Karrenbeld A, Koudstaal J, Gouw AS, Sluiter WJ, et al. Clinical relevance of transforming growth factor alpha, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors. Hepatology. 1998;28:971–9.PubMedCrossRef De Jong KP, Stellema R, Karrenbeld A, Koudstaal J, Gouw AS, Sluiter WJ, et al. Clinical relevance of transforming growth factor alpha, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors. Hepatology. 1998;28:971–9.PubMedCrossRef
13.
Zurück zum Zitat Nanashima A, Yamaguchi H, Sawai T, Yasutake T, Tsuji T, Jibiki M, et al. Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumors and prognosis after hepatic resection. J Gastroenterol Hepatol. 1999;14:1004–9.PubMedCrossRef Nanashima A, Yamaguchi H, Sawai T, Yasutake T, Tsuji T, Jibiki M, et al. Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumors and prognosis after hepatic resection. J Gastroenterol Hepatol. 1999;14:1004–9.PubMedCrossRef
14.
Zurück zum Zitat Wielenga VJ, Heider KH, Offerhaus GJ, Adolf GR, van den Berg FM, Ponta H, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993;53:4754–6.PubMed Wielenga VJ, Heider KH, Offerhaus GJ, Adolf GR, van den Berg FM, Ponta H, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993;53:4754–6.PubMed
15.
Zurück zum Zitat Nihei Z, Ichikawa W, Kojima K, Togo S, Miyanaga T, Hirayama R, et al. The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer. Surg Today. 1996;26:760–1.PubMedCrossRef Nihei Z, Ichikawa W, Kojima K, Togo S, Miyanaga T, Hirayama R, et al. The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer. Surg Today. 1996;26:760–1.PubMedCrossRef
16.
Zurück zum Zitat Ohji Y, Yao T, Eguchi T, Yamada T, Hirahashi M, Iida M, et al. Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep. 2007;17:525–30.PubMed Ohji Y, Yao T, Eguchi T, Yamada T, Hirahashi M, Iida M, et al. Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep. 2007;17:525–30.PubMed
17.
Zurück zum Zitat Fujita S, Taniguchi H, Yao T, Shimoda T, Ueno H, Hirai T, et al. Multi-institutional study of risk factors of liver metastasis from colorectal cancer: correlation with CD10 expression. Int J Colorectal Dis. 2010;25:681–6.PubMedCrossRef Fujita S, Taniguchi H, Yao T, Shimoda T, Ueno H, Hirai T, et al. Multi-institutional study of risk factors of liver metastasis from colorectal cancer: correlation with CD10 expression. Int J Colorectal Dis. 2010;25:681–6.PubMedCrossRef
18.
Zurück zum Zitat Brabletz S, Schmalhofer O, Brabletz T. Gastrointestinal stem cells in development and cancer. J Pathol. 2009;217:307–17.PubMedCrossRef Brabletz S, Schmalhofer O, Brabletz T. Gastrointestinal stem cells in development and cancer. J Pathol. 2009;217:307–17.PubMedCrossRef
19.
Zurück zum Zitat Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumor progression. Nat Rev Cancer. 2005;5:744–9.PubMedCrossRef Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumor progression. Nat Rev Cancer. 2005;5:744–9.PubMedCrossRef
20.
Zurück zum Zitat Fodde R, Brabletz T. Wnt/β-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19:150–8.PubMedCrossRef Fodde R, Brabletz T. Wnt/β-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19:150–8.PubMedCrossRef
21.
Zurück zum Zitat Brabletz T, Jung A, Hermann K, Günther K, Hohenberger W, Kirchner T. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract. 1998;194:701–4.PubMed Brabletz T, Jung A, Hermann K, Günther K, Hohenberger W, Kirchner T. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract. 1998;194:701–4.PubMed
22.
Zurück zum Zitat Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA. 2001;98:10356–61.PubMedCrossRef Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA. 2001;98:10356–61.PubMedCrossRef
23.
24.
Zurück zum Zitat Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis: a look outside the nucleus. Science. 2000;287:1606–9.PubMedCrossRef Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis: a look outside the nucleus. Science. 2000;287:1606–9.PubMedCrossRef
25.
Zurück zum Zitat Brembeck FH, Rosário M, Birchmeier W. Balancing cell adhesion and Wnt signaling, the key role of β-catenin. Curr Opin Genet Dev. 2006;16:51–9.PubMedCrossRef Brembeck FH, Rosário M, Birchmeier W. Balancing cell adhesion and Wnt signaling, the key role of β-catenin. Curr Opin Genet Dev. 2006;16:51–9.PubMedCrossRef
26.
Zurück zum Zitat Pinto D, Clevers H. Wnt, stem cells and cancer in the intestine. Biol Cell. 2005;97:185–96.PubMedCrossRef Pinto D, Clevers H. Wnt, stem cells and cancer in the intestine. Biol Cell. 2005;97:185–96.PubMedCrossRef
27.
Zurück zum Zitat Fodde R, Brabletz T. WNT/β-catenin signalling in cancer stemness and malignant behaviour. Cell Biol. 2007;19:150–8. Fodde R, Brabletz T. WNT/β-catenin signalling in cancer stemness and malignant behaviour. Cell Biol. 2007;19:150–8.
28.
Zurück zum Zitat Pancione M, Forte N, Fucci A, Sabatino L, Febbraro A, Di Blasi A, et al. Prognostic role of beta-catenin and p53 expression in the metastatic progression of sporadic colorectal cancer. Hum Pathol. 2010;41:867–76.PubMedCrossRef Pancione M, Forte N, Fucci A, Sabatino L, Febbraro A, Di Blasi A, et al. Prognostic role of beta-catenin and p53 expression in the metastatic progression of sporadic colorectal cancer. Hum Pathol. 2010;41:867–76.PubMedCrossRef
29.
Zurück zum Zitat Bandapalli OR, Dihlmann S, Helwa R, Macher-Goeppinger S, Weitz J, Schirmacher P, et al. Transcriptional activation of the beta-catenin gene at the invasion front of colorectal liver metastases. J Pathol. 2009;218:370–9.PubMedCrossRef Bandapalli OR, Dihlmann S, Helwa R, Macher-Goeppinger S, Weitz J, Schirmacher P, et al. Transcriptional activation of the beta-catenin gene at the invasion front of colorectal liver metastases. J Pathol. 2009;218:370–9.PubMedCrossRef
30.
Zurück zum Zitat Greene FL, Page DL. AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002. p. 127–38. Greene FL, Page DL. AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002. p. 127–38.
31.
Zurück zum Zitat Romeo S, Bovée JV, Grogan SP, Taminiau AH, Eilers PH, Leton-Jansen AM, et al. Chondromyxoid fibroma resembles in vitro chondrogenesis, though differs in expression of signalling molecules. J Pathol. 2005;206:135–42.PubMedCrossRef Romeo S, Bovée JV, Grogan SP, Taminiau AH, Eilers PH, Leton-Jansen AM, et al. Chondromyxoid fibroma resembles in vitro chondrogenesis, though differs in expression of signalling molecules. J Pathol. 2005;206:135–42.PubMedCrossRef
32.
Zurück zum Zitat Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996;272:1023–6.PubMedCrossRef Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996;272:1023–6.PubMedCrossRef
33.
Zurück zum Zitat Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science. 1997;275:1790–2.PubMedCrossRef Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science. 1997;275:1790–2.PubMedCrossRef
34.
Zurück zum Zitat Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997;275:1784–7.PubMedCrossRef Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997;275:1784–7.PubMedCrossRef
35.
Zurück zum Zitat Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275:1787–90.PubMedCrossRef Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275:1787–90.PubMedCrossRef
36.
Zurück zum Zitat Iwao K, Nakamori S, Kameyama M, Imaoka S, Kinoshita M, Fukui T, et al. Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. Cancer Res. 1998;58:1021–6.PubMed Iwao K, Nakamori S, Kameyama M, Imaoka S, Kinoshita M, Fukui T, et al. Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. Cancer Res. 1998;58:1021–6.PubMed
37.
Zurück zum Zitat Suzuki H, Masuda N, Shimura T, Araki K, Kobayashi T, Tsutsumi S, et al. Nuclear beta-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma. Anticancer Res. 2008;28:1821–30.PubMed Suzuki H, Masuda N, Shimura T, Araki K, Kobayashi T, Tsutsumi S, et al. Nuclear beta-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma. Anticancer Res. 2008;28:1821–30.PubMed
38.
Zurück zum Zitat Zhang B, Ougolkov A, Yamashita K, Takahashi Y, Mai M, Minamoto T. beta-Catenin and ras oncogenes detect most human colorectal cancer. Clin Cancer Res. 2003;9:3073–9.PubMed Zhang B, Ougolkov A, Yamashita K, Takahashi Y, Mai M, Minamoto T. beta-Catenin and ras oncogenes detect most human colorectal cancer. Clin Cancer Res. 2003;9:3073–9.PubMed
39.
Zurück zum Zitat Baldus SE, Mönig SP, Huxel S, Landsberg S, Hanisch FG, Engelmann K, et al. MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res. 2004;10:2790–6.PubMedCrossRef Baldus SE, Mönig SP, Huxel S, Landsberg S, Hanisch FG, Engelmann K, et al. MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res. 2004;10:2790–6.PubMedCrossRef
Metadaten
Titel
Prognostic Value of Nuclear β-catenin Overexpression at Invasive Front in Colorectal Cancer for Synchronous Liver Metastasis
verfasst von
Lin Wang, MD
Hongxia Cheng, MD
Ying Liu, MD
Lei Wang, MD
Wenbin Yu, MD
Guangyong Zhang, MD
Bo Chen, MD
Zhiyong Yu, MD
Sanyuan Hu, MD
Publikationsdatum
01.06.2011
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 6/2011
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1519-9

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