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Erschienen in: Clinical and Translational Oncology 5/2014

01.05.2014 | Research Article

Overexpression of nuclear β-catenin at invasive front in rectal carcinoma is associated with lymph node metastasis and poor prognosis

verfasst von: L. Wang, X. Zhang, Z. Li, J. Chai, G. Zhang, Z. Yu, Y. Cheng, S. Hu

Erschienen in: Clinical and Translational Oncology | Ausgabe 5/2014

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Abstract

Background

This study aims to investigate whether nuclear β-catenin overexpression at invasive front in rectal carcinoma is associated with lymph node metastasis and prognosis.

Methods

Immunohistochemistry was adopted to detect the expression of β-catenin in rectal carcinoma and lymph node metastatic lesions. Spearman’s rank correlation analysis and Tukey’s test were used to evaluate the association between nuclear β-catenin expression at invasive front in rectal carcinoma and lymph node metastasis. Kaplan–Meier method and multivariate Cox regression model were used to evaluate the prognostic value of nuclear β-catenin overexpression at invasive front in rectal carcinoma for disease-free survival (DFS) and overall survival (OS).

Results

Overexpression of nuclear β-catenin at the invasive front in rectal carcinoma in stage III-N2 was significantly higher than that in stage III-N1 (73.4 vs. 40.4 %, P < 0.001). Nuclear β-catenin expression at the invasive front in rectal carcinoma was associated with the expression of nuclear β-catenin in corresponding lymph node metastatic lesions (r = 0.297, P < 0.001). Overexpression of nuclear β-catenin at the invasive front in rectal carcinoma was correlated with the number of metastatic lymph nodes (P < 0.001). Patients with nuclear β-catenin overexpression at the invasive front in rectal carcinoma had poor DFS (P = 0.002) and OS (P = 0.003). Moreover, overexpression of nuclear β-catenin at the invasive front was an independent prognosticator for unfavorable DFS and OS (P = 0.002 and 0.001).

Conclusions

Our findings suggest that overexpression of nuclear β-catenin at the invasive front in rectal carcinoma may be a useful marker to evaluate lymph node metastasis, as well as a promising predictor of poor prognosis.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef
2.
Zurück zum Zitat Wang YX, Zhang XY, Zhang BF, Yang CQ, Chen XM, Gao HJ. Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 2010;11:50–4.PubMedCrossRef Wang YX, Zhang XY, Zhang BF, Yang CQ, Chen XM, Gao HJ. Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 2010;11:50–4.PubMedCrossRef
3.
Zurück zum Zitat Punt CJ, Tol J. More is less-combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol. 2009;6:731–3.PubMedCrossRef Punt CJ, Tol J. More is less-combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol. 2009;6:731–3.PubMedCrossRef
4.
Zurück zum Zitat Hong Y, Downey T, Eu KW, Koh PK, Cheah PY. A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clin Exp Metastasis. 2010;27:83–90.PubMedCrossRef Hong Y, Downey T, Eu KW, Koh PK, Cheah PY. A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clin Exp Metastasis. 2010;27:83–90.PubMedCrossRef
5.
Zurück zum Zitat Obeidat NA, Pradel FG, Zuckerman IH, DeLisle S, Mullins CD. Outcomes of irinotecan-based chemotherapy regimens in elderly. Medicare patients with metastatic colorectal cancer. Am J Geriatr Pharmacother. 2009;7:343–54.PubMedCrossRef Obeidat NA, Pradel FG, Zuckerman IH, DeLisle S, Mullins CD. Outcomes of irinotecan-based chemotherapy regimens in elderly. Medicare patients with metastatic colorectal cancer. Am J Geriatr Pharmacother. 2009;7:343–54.PubMedCrossRef
6.
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
7.
Zurück zum Zitat Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumour 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 tumour progression. Nat Rev Cancer. 2005;5:744–9.PubMedCrossRef
8.
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
9.
Zurück zum Zitat El-Gendi S, Al-Gendi A. Assessment of tumor budding in colorectal carcinoma: correlation with β-catenin nuclear expression. J Egypt Natl Canc Inst. 2011;23:1–9.PubMedCrossRef El-Gendi S, Al-Gendi A. Assessment of tumor budding in colorectal carcinoma: correlation with β-catenin nuclear expression. J Egypt Natl Canc Inst. 2011;23:1–9.PubMedCrossRef
10.
Zurück zum Zitat Wang L, Cheng H, Liu Y, Wang L, Yu W, Zhang G, et al. Prognostic value of nuclear β-catenin overexpression at invasive front in colorectal cancer for synchronous liver metastasis. Ann Surg Oncol. 2011;18:1553–9.PubMedCrossRef Wang L, Cheng H, Liu Y, Wang L, Yu W, Zhang G, et al. Prognostic value of nuclear β-catenin overexpression at invasive front in colorectal cancer for synchronous liver metastasis. Ann Surg Oncol. 2011;18:1553–9.PubMedCrossRef
11.
Zurück zum Zitat Horst D, Reu S, Kriegl L, Engel J, Kirchner T, Jung A. The intratumoral distribution of nuclear beta-catenin is a prognostic marker in colon cancer. Cancer. 2009;115:2063–70.PubMedCrossRef Horst D, Reu S, Kriegl L, Engel J, Kirchner T, Jung A. The intratumoral distribution of nuclear beta-catenin is a prognostic marker in colon cancer. Cancer. 2009;115:2063–70.PubMedCrossRef
12.
Zurück zum Zitat Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol. 2010;28:1481–8.PubMedCentralPubMedCrossRef Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol. 2010;28:1481–8.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Davicioni E, Anderson JR, Buckley JD, Meyer WH, Triche TJ. Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the children’s oncology group. J Clin Oncol. 2010;28:1240–6.PubMedCentralPubMedCrossRef Davicioni E, Anderson JR, Buckley JD, Meyer WH, Triche TJ. Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the children’s oncology group. J Clin Oncol. 2010;28:1240–6.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Ferrari A, Miceli R, Meazza C, Casanova M, Favini F, Morosi C, et al. Comparison of the prognostic value of assessing tumor diameter versus tumor volume at diagnosis or in response to initial chemotherapy in rhabdomyosarcoma. J Clin Oncol. 2010;28:1322–8.PubMedCrossRef Ferrari A, Miceli R, Meazza C, Casanova M, Favini F, Morosi C, et al. Comparison of the prognostic value of assessing tumor diameter versus tumor volume at diagnosis or in response to initial chemotherapy in rhabdomyosarcoma. J Clin Oncol. 2010;28:1322–8.PubMedCrossRef
15.
Zurück zum Zitat Ejlertsen B, Jensen MB, Nielsen KV, Balslev E, Rasmussen BB, Willemoe GL, et al. HER2, TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients. J Clin Oncol. 2010;28:984–90.PubMedCrossRef Ejlertsen B, Jensen MB, Nielsen KV, Balslev E, Rasmussen BB, Willemoe GL, et al. HER2, TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients. J Clin Oncol. 2010;28:984–90.PubMedCrossRef
16.
Zurück zum Zitat Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28:375–9.PubMedCrossRef Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28:375–9.PubMedCrossRef
17.
Zurück zum Zitat Stephen EB, David BR, Carolyn CC, April FG, Frederick GL, Andy T. Colon and rectum. AJCC Cancer Staging Manual. New York: Springer; 2010. p. 143–64. Stephen EB, David BR, Carolyn CC, April FG, Frederick GL, Andy T. Colon and rectum. AJCC Cancer Staging Manual. New York: Springer; 2010. p. 143–64.
18.
Zurück zum Zitat Umemura K, Takagi S, Shimada T, Masuda T, Shiga H, Takahashi S, et al. Prognostic and diagnostic significance of tumor budding associated with β-catenin expression in submucosal invasive colorectal carcinoma. Tohoku J Exp Med. 2012;229:53–9.CrossRef Umemura K, Takagi S, Shimada T, Masuda T, Shiga H, Takahashi S, et al. Prognostic and diagnostic significance of tumor budding associated with β-catenin expression in submucosal invasive colorectal carcinoma. Tohoku J Exp Med. 2012;229:53–9.CrossRef
19.
Zurück zum Zitat Jang KY, Kim YN, Bae JS, Chung MJ, Moon WS, Kang MJ, et al. Expression of cyclin D1 is associated with β-catenin expression and correlates with good prognosis in colorectal adenocarcinoma. Transl Oncol. 2012;5:370–8.PubMedCentralPubMedCrossRef Jang KY, Kim YN, Bae JS, Chung MJ, Moon WS, Kang MJ, et al. Expression of cyclin D1 is associated with β-catenin expression and correlates with good prognosis in colorectal adenocarcinoma. Transl Oncol. 2012;5:370–8.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Stanczak A, Stec R, Bodnar L, Olszewski W, Cichowicz M, Kozlowski W, et al. Prognostic significance of Wnt-1, β-catenin and E-cadherin expression in advanced colorectal carcinoma. Pathol Oncol Res. 2011;17:955–63.PubMedCentralPubMedCrossRef Stanczak A, Stec R, Bodnar L, Olszewski W, Cichowicz M, Kozlowski W, et al. Prognostic significance of Wnt-1, β-catenin and E-cadherin expression in advanced colorectal carcinoma. Pathol Oncol Res. 2011;17:955–63.PubMedCentralPubMedCrossRef
Metadaten
Titel
Overexpression of nuclear β-catenin at invasive front in rectal carcinoma is associated with lymph node metastasis and poor prognosis
verfasst von
L. Wang
X. Zhang
Z. Li
J. Chai
G. Zhang
Z. Yu
Y. Cheng
S. Hu
Publikationsdatum
01.05.2014
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 5/2014
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1108-z

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