Differential β-catenin expression levels are associated with morphological features and prognosis of colorectal cancer

Gao,Zhao-Hua; Lu,Chong; Wang,Mei-Xian; Han,Yi; Guo,Li-Juan

doi:10.3892/ol.2014.2433

Differential β-catenin expression levels are associated with morphological features and prognosis of colorectal cancer

Authors:
- Zhao-Hua Gao
- Chong Lu
- Mei-Xian Wang
- Yi Han
- Li-Juan Guo
View Affiliations

Affiliations: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Tumor Pathology and Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Surgery, Shenyang Red Cross Hospital, Shenyang, Liaoning 110013, P.R. China
Published online on: August 11, 2014 https://doi.org/10.3892/ol.2014.2433
Pages: 2069-2076

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

β‑catenin, an epithelial‑mesenchymal transition (EMT)‑associated marker, is key in the progression of colorectal cancer (CRC). However, the prognostic significance of β‑catenin expression in patients with CRC remains controversial. In the present study, the expression of β‑catenin at the tumor invasive front and the tumor center was investigated, and the correlations amongst β‑catenin differential expression patterns and the clinicopathological characteristics and prognosis of CRC patients were determined. In total, 181 patients that were diagnosed with CRC (as determined by histopathological evaluation) and subjected to surgical resection at the First Hospital of China Medical University between 2000 and 2001 were examined, and CRC specimens were obtained. Immunohistochemical (IHC) staining of β‑catenin was performed for each specimen. The nuclear β‑catenin expression levels were identified to be signiﬁcantly lower in the tumor center than at the tumor invasive front (immunoreactivity score, 0.05±0.303 versus 2.18±3.917; P<0.001). The presence of nuclear β‑catenin overexpression at the tumor invasive front was found to be correlated with the tumor, node, metastasis stage (P=0.020), lymph node metastasis (P=0.016) and histological differentiation (P=0.006). Survival analysis revealed that reduced membranous expression levels and increased nuclear expression levels of β‑catenin were statistically significantly associated with poor survival times. Furthermore, differential β‑catenin expression levels were associated with aggressive morphological features, EMT and a poor prognosis in CRC. Therefore, IHC analysis of β‑catenin is considered to be a useful marker to predict the prognosis in patients with CRC.

View Figures

View References

1	de Krijger I, Mekenkamp LJ, Punt CJ and Nagtegaal ID: MicroRNAs in colorectal cancer metastasis. J Pathol. 224:438–447. 2011.
2	Xu AG, Yu ZJ, Jiang B, et al: Colorectal cancer in Guangdong Province of China: a demographic and anatomic survey. World J Gastroenterol. 16:960–965. 2010.
3	Zlobec I and Lugli A: Invasive front of colorectal cancer: dynamic interface of pro-/anti-tumor factors. World J Gastroenterol. 15:5898–5906. 2009.
4	Natalwala A, Spychal R and Tselepis C: Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 14:3792–3797. 2008.
5	Brabletz T, Jung A, Hermann K, et al: Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract. 194:701–704. 1998.
6	Guarino M, Rubino B and Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 39:305–318. 2007.
7	Sánchez-Tilló E, de Barrios O, Siles L, Cuatrecasas M, Castells A and Postigo A: Beta-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator ZEB1 to regulate tumor invasiveness. Proc Natl Acad Sci USA. 108:19204–19209. 2011.
8	Jang TJ: Expression of E-cadherin and β-catenin is altered at tumor budding sites, whose number is associated with the progression of colorectal carcinoma. Korean J Pathol. 43:523–527. 2009.
9	International Agency for Research on Cancer. World Health Organization classification of tumours. Pathology and genetics of tumours of the digestive system. IARC Press; Lyon, France: 2000
10	Edge SBD and Compton C: AJCC Cancer Staging Manual. 7th edition. JAMA. 304. pp. 1726–1727. 2010
11	Ru GQ, Wang HJ, Xu WJ and Zhao ZS: Upregulation of Twist in gastric carcinoma associated with tumor invasion and poor prognosis. Pathol Oncol Res. 17:341–347. 2011.
12	Sinicrope FA, Ruan SB, Cleary KR, et al: bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 55:237–241. 1995.
13	Zhu JL, Song YX, Wang ZN, et al: The clinical significance of mesenchyme forkhead 1 (FoxC2) in gastric carcinoma. Histopathology. 62:1038–1048. 2013.
14	Boo YJ, Park JM, Kim J, et al: L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol. 14:1703–1711. 2007.
15	Baldus SE, Mönig SP, Huxel S, 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. 10:2790–2796. 2004.
16	Grünert S, Jechlinger M and Beug H: Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 4:657–665. 2003.
17	Hugo H, Ackland ML, Blick T, et al: Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 213:374–383. 2007.
18	Conacci-Sorrell M, Simcha I, Ben-Yedidia T, et al: Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J Cell Biol. 163:847–857. 2003.
19	Gavert N and Ben-Ze’ev A: Epithelial-mesenchymal transition and the invasive potential of tumors. Trends Mol Med. 14:199–209. 2008.
20	Mårtensson A, Oberg A, Jung A, et al: Beta-catenin expression in relation to genetic instability and prognosis in colorectal cancer. Oncol Rep. 17:447–452. 2007.
21	Chen Z, He X, Jia M, et al: Beta-catenin overexpression in the nucleus predicts progress disease and unfavourable survival in colorectal cancer: a meta-analysis. PloS One. 8:e638542013.
22	Hörkkö TT, Klintrup K, Mäkinen JM, et al: Budding invasive margin and prognosis in colorectal cancer - no direct association with beta-catenin expression. Eur J Cancer. 42:964–971. 2006.
23	Roca F, Mauro LV, Morandi A, et al: Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2) in patients with colorectal carcinoma. J Surg Oncol. 93:151–160. 2006.
24	Lee SJ, Choi SY, Kim WJ, et al: Combined aberrant expression of E-cadherin and S100A4, but not beta-catenin is associated with disease-free survival and overall survival in colorectal cancer patients. Diagn Pathol. 8:992013.
25	Wangefjord S, Brändstedt J, Lindquist KE, et al: Associations of beta-catenin alterations and MSI screening status with expression of key cell cycle regulating proteins and survival from colorectal cancer. Diagn Pathol. 8:102013.