Correlation of CD146 expression and clinicopathological characteristics in esophageal squamous cell carcinoma

Li,Yan; Yu,Jin-Ming; Zhan,Xue-Mei; Liu,Li-Li; Jin,Ning; Zhang,Yan-Xia

doi:10.3892/ol.2014.2227

Correlation of CD146 expression and clinicopathological characteristics in esophageal squamous cell carcinoma

Authors:
- Yan Li
- Jin-Ming Yu
- Xue-Mei Zhan
- Li-Li Liu
- Ning Jin
- Yan-Xia Zhang
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Affiliations: Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong 250117, P.R. China, Department of Pathology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Department of Radiation Oncology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China
Published online on: June 5, 2014 https://doi.org/10.3892/ol.2014.2227
Pages: 859-863

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Abstract

CD146, a cell adhesion molecule, is found in normal and tumor tissues. The level of its expression has been found to directly correlate with tumor progression and metastatic potential. The objective of this study was to investigate the expression of CD146 in esophageal squamous cell carcinoma (ESCC) and its correlation with clinicopathological parameters. Tumor specimens were collected from 63 patients with ESCC who underwent complete resection. We analyzed the CD146 expression levels in ESCC by immunohistochemistry. The expression of CD146 was detected and it was observed to correlate with clinicopathological parameters. Sixty‑three cases of normal squamous mucosa were included for comparison. CD146 expression was identified in 46.0% (29/63) of the ESCC samples, and no positive (weak to moderate or moderate to strong) expression was found in the normal squamous epithelium samples (χ2=27.248; P<0.0001). CD146 expression was associated with lymph node metastasis (χ2=5.117; P=0.024) and advanced clinical stage (χ2=4.661; P=0.031). CD146 expression was one of the significant predictors of survival (hazard ratio, 2.838; 95% confidence interval 1.102‑7.305). The overexpression of the CD146 gene was one of the important phenotypes and characteristics in ESCC carcinomatous change. We found that CD146 expression was associated with lymph node metastasis and advanced clinical stage, and was an indicator of poor prognosis in ESCC patients. CD146 may prove to be an important tumor marker for the individualized treatment for ESCC.

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1	Li JS, Ying JM, Wang XM, et al: Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma. Chin J Cancer. 32:3–11. 2013.
2	Sarbia M, Ott N, Pühringer-Oppermann F and Brucher BL: The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus. Br J Cancer. 97:1404–1408. 2007.
3	Li C, Li Z, Zhu M, et al: Clinicopathological and prognostic significance of survivin over-expression in patients with esophageal squamous cell carcinoma: a meta-analysis. PLoS One. 7:e447642012.
4	Kuo KT, Chow KC, Wu YC, et al: Clinicopathologic significance of cyclooxygenase-2 overexpression in esophageal squamous cell carcinoma. Ann Thorac Surg. 76:909–914. 2003.
5	Lehmann JM, Riethmuller G and Johnson JP: MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci USA. 86:9891–9895. 1989.
6	Ouhtit A, Gaur RL, Abd Elmageed ZY, et al: Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146. Biochim Biophys Acta. 1795:130–136. 2009.
7	Melnikova VO, Balasubramanian K, Villares GJ, et al: Crosstalk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis. J Biol Chem. 284:28845–28855. 2009.
8	Wu GJ, Peng Q, Fu P, et al: Ectopical expression of human MUC18 increases metastasis of human prostate cancer cells. Gene. 327:201–213. 2004.
9	Aldovini D, Demichelis F, Doglioni C, et al: M- CAM expression as marker of poor prognosis in epithelial ovarian cancer. Int J Cancer. 119:1920–1926. 2006.
10	Zabouo G, Imbert AM, Jacquemier J, et al: CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines. Breast Cancer Res. 11:R12009.
11	Gabbert HZ, Shimoda T, Hainaut P, et al: Tumours of the oesophagus. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Digestive System. Hamilton SR and Alaltonen LA: IARC Press; Lyon: pp. 10–16. 2000
12	TNM Classification of the Esophagus. International Union Against Cancer; 6th edition. J Willy & Sons; New York, NY: pp. 2–25. 2002
13	Wang W, Yang ZL, Liu JQ, Jiang S and Miao XY: Identification of CD146 expression, angiogenesis, and lymphangiogenesis as progression, metastasis, and poor prognosis related markers for gallbladder adenocarcinoma. Tumour Biol. 33:173–182. 2012.
14	Luo Y, Zheng C, Zhang J, et al: Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration. Oncogene. 31:306–321. 2012.
15	Luca M, Hunt B, Bucana CD, et al: Direct correlation between MUC18 expression and metastatic potential of human melanoma cells. Melanoma Res. 3:35–41. 1993.
16	Johnson JP: Cell adhesion molecules in the development and progression of malignant melanoma. 18:345–357. 1999.
17	Xie S, Luca M, Huang S, et al: Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res. 57:2295–2303. 1997.
18	Zabouo G, Imbert AM, Jacquemier J, et al: CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines. Breast Cancer Res. 11:R12009.
19	Kristiansen G, Yu Y, Schluns K, et al: Expression of the cell adhesion molecule CD146/MCAM in non-small cell lung cancer. Anal Cell Pathol. 25:77–81. 2003.
20	Liu WF, Ji SR, Sun JJ, et al: CD146 Expression correlates with epithelial-mesenchymal transition markers and a poor prognosis in gastric cancer. Int J Mol Sci. 13:6399–6406. 2012.
21	Shih I-M, Nesbit M, Herlyn M and Kurman RJ: A new Mel-CAM (CD146)-specific monoclonal antibody, MN-4, on paraffin-embedded tissue. Mod Pathol. 11:1098–1106. 1998.
22	Zeng Q, Li W, Lu D, et al: CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer. Proc Natl Acad Sci USA. 109:1127–1132. 2012.
23	Tsai JH and Yang J: Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 27:2192–2206. 2013.
24	Bardin N, Anfosso F, Masse JM, et al: Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion. Blood. 98:3677–3684. 2001.
25	Delorme B, Ringe J, Gallay N, et al: Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells. Blood. 111:2631–2635. 2008.
26	Tanaka T, Ishiguro H, Kuwabara Y, et al: Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. J Exp Clin Cancer Res. 29:832010.
27	Sundar SS and Ganesan TS: Role of lymphangiogenesis in cancer. J Clin Oncol. 25:4298–4207. 2007.
28	Nathanson SD: Insights into the mechanisms of lymph node metastasis. Cancer. 98:413–423. 2003.