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Erschienen in: Clinical and Translational Oncology 2/2014

01.02.2014 | Research Article

MCAM expression is associated with poor prognosis in non-small cell lung cancer

verfasst von: X. Zhang, Z. Wang, Y. Kang, X. Li, X. Ma, L. Ma

Erschienen in: Clinical and Translational Oncology | Ausgabe 2/2014

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Abstract

Background

MCAM has been recently identified as a biomarker for epithelial–mesenchymal transition (EMT) and is potentially involved in metastasis of cancer. The current study aimed at investigating the expression of MCAM in non-small-cell lung cancer (NSCLC) and its clinico-pathological significance.

Methods

A follow-up analysis was performed on 118 patients with NSCLC resected by lobectomy or pneumectomy with systematic lymph node dissection. All patients were followed for 6–60 months. Immunostaining of tissue sections from primary tumors and their lymph node metastasis was performed and evaluated using monoclonal antibody against MCAM, E-cadherin, and vimentin. Correlations were investigated between MCAM immunostaining in primary tumors and E-cadherin, vimentin immunostaining, lymph node metastasis, and survival.

Results

MCAM protein expression was found in 46.61 % of squamous cell carcinomas and 37.47 % of adenocarcinomas; MCAM expression positively correlated with vimentin, but inversely with E-cadherin (both P values <0.05). There were significant correlations between the MCAM immunostaining score in primary tumors and in their lymph node metastasis (P = 0.03). According to the Kaplan–Meier survival estimate, the level of MCAM expression in primary tumors was a statistically significant prognostic factor (P < 0.05).

Conclusions

MCAM expression in surgically treated NSCLC is clearly associated with lymph node metastasis and poor prognosis.
Literatur
1.
2.
Zurück zum Zitat Ettinger DS, Akerley W, Borghaei H, Chang A, Cheney RT, Chirieac LR et al. NCCN Clinical Practice Guidelines in Oncology Non-small cell lung cancer Version 3. 2011. National comprehensive cancer network. http://www.nccn.com (2011) Accessed 7 June 2011. Ettinger DS, Akerley W, Borghaei H, Chang A, Cheney RT, Chirieac LR et al. NCCN Clinical Practice Guidelines in Oncology Non-small cell lung cancer Version 3. 2011. National comprehensive cancer network. http://​www.​nccn.​com (2011) Accessed 7 June 2011.
3.
Zurück zum Zitat Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I non-small cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California cancer registry from 1989 to 2003. Cancer. 2007;110(7):1532–41.PubMedCrossRef Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I non-small cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California cancer registry from 1989 to 2003. Cancer. 2007;110(7):1532–41.PubMedCrossRef
4.
Zurück zum Zitat Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;350(4):379–92.PubMedCrossRef Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;350(4):379–92.PubMedCrossRef
5.
Zurück zum Zitat Thiery JP. Epithelial–mesenchymal transition in tumor progression. Nat Rev Cancer. 2002;2(6):442–54.PubMedCrossRef Thiery JP. Epithelial–mesenchymal transition in tumor progression. Nat Rev Cancer. 2002;2(6):442–54.PubMedCrossRef
6.
Zurück zum Zitat Huber MA, Kraut N, Beug H. Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17(5):548–58.PubMedCrossRef Huber MA, Kraut N, Beug H. Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17(5):548–58.PubMedCrossRef
7.
Zurück zum Zitat Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial–mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172(7):973–81.PubMedCrossRef Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial–mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172(7):973–81.PubMedCrossRef
9.
Zurück zum Zitat Sers C, Kirsch K, Rothbacher U, Riethmuller G, Johnson JP. Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc Natl Acad Sci USA. 1993;90(18):8514–8.PubMedCrossRef Sers C, Kirsch K, Rothbacher U, Riethmuller G, Johnson JP. Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc Natl Acad Sci USA. 1993;90(18):8514–8.PubMedCrossRef
10.
Zurück zum Zitat Wang Z, Yan X. CD146, a multi-functional molecule beyond adhesion. Cancer Lett. 2013;330(2):150–62.PubMedCrossRef Wang Z, Yan X. CD146, a multi-functional molecule beyond adhesion. Cancer Lett. 2013;330(2):150–62.PubMedCrossRef
11.
Zurück zum Zitat Bardin N, Anfosso F, Masse JM, Cramer E, Sabatier F, Le Bivic A, et al. Identification of CD146 as a component of the endothelial junction involved in the control of cell–cell cohesion. Blood. 2001;98(13):3677–84.PubMedCrossRef Bardin N, Anfosso F, Masse JM, Cramer E, Sabatier F, Le Bivic A, et al. Identification of CD146 as a component of the endothelial junction involved in the control of cell–cell cohesion. Blood. 2001;98(13):3677–84.PubMedCrossRef
12.
Zurück zum Zitat Shih IM, Speicher D, Hsu MY, Levine E, Herlyn M. Melanoma cell–cell interactions are mediated through heterophilic Mel-CAM/ligand adhesion. Cancer Res. 1997;57(17):3835–40.PubMed Shih IM, Speicher D, Hsu MY, Levine E, Herlyn M. Melanoma cell–cell interactions are mediated through heterophilic Mel-CAM/ligand adhesion. Cancer Res. 1997;57(17):3835–40.PubMed
13.
Zurück zum Zitat Wu GJ, Peng Q, Fu P, Wang SW, Chiang CF, Dillehay DL, et al. Ectopical expression of human MUC18 increases metastasis of human prostate cancer cells. Gene. 2004;327(2):201–13.PubMedCrossRef Wu GJ, Peng Q, Fu P, Wang SW, Chiang CF, Dillehay DL, et al. Ectopical expression of human MUC18 increases metastasis of human prostate cancer cells. Gene. 2004;327(2):201–13.PubMedCrossRef
14.
Zurück zum Zitat Aldovini D, Demichelis F, Doglioni C, Di Vizio D, Galligioni E, Brugnara S, et al. MCAM expression as marker of poor prognosis in epithelial ovarian cancer. Int J Cancer. 2006;119(8):1920–6.PubMedCrossRef Aldovini D, Demichelis F, Doglioni C, Di Vizio D, Galligioni E, Brugnara S, et al. MCAM expression as marker of poor prognosis in epithelial ovarian cancer. Int J Cancer. 2006;119(8):1920–6.PubMedCrossRef
15.
Zurück zum Zitat Zabouo G, Imbert AM, Jacquemier J, Finetti P, Moreau T, Esterni B, 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. 2009;11(1):R1.PubMedCentralPubMedCrossRef Zabouo G, Imbert AM, Jacquemier J, Finetti P, Moreau T, Esterni B, 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. 2009;11(1):R1.PubMedCentralPubMedCrossRef
16.
Zurück zum Zitat Bidlingmaier S, He J, Wang Y, An F, Feng J, Barbone D, et al. Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma. Cancer Res. 2009;69(4):1570–7.PubMedCentralPubMedCrossRef Bidlingmaier S, He J, Wang Y, An F, Feng J, Barbone D, et al. Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma. Cancer Res. 2009;69(4):1570–7.PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Wang W, Yang ZL, Liu JQ, Jiang S, Miao XY. Identification of CD146 expression, angiogenesis, and lymphangiogenesis as progression, metastasis, and poor-prognosis related markers for gallbladder adenocarcinoma. Tumor Biol. 2012;33(1):173–82.CrossRef Wang W, Yang ZL, Liu JQ, Jiang S, Miao XY. Identification of CD146 expression, angiogenesis, and lymphangiogenesis as progression, metastasis, and poor-prognosis related markers for gallbladder adenocarcinoma. Tumor Biol. 2012;33(1):173–82.CrossRef
18.
Zurück zum Zitat Liu WF, Ji SR, Sun JJ, Zhang Y, Liu ZY, Liang AB, et al. CD146 expression correlates with epithelial–mesenchymal transition markers and a poor prognosis in gastric cancer. Int J Mol Sci. 2012;13(5):6399–406.PubMedCentralPubMedCrossRef Liu WF, Ji SR, Sun JJ, Zhang Y, Liu ZY, Liang AB, et al. CD146 expression correlates with epithelial–mesenchymal transition markers and a poor prognosis in gastric cancer. Int J Mol Sci. 2012;13(5):6399–406.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Schlagbauer-Wadl H, Jansen B, Muller M, Polterauer P, Wolff K, Eichler HG, et al. Influence of MUC18/MCAM/CD146 expression on human melanoma growth and metastasis in SCID mice. Int J Cancer. 1999;81(6):951–5.PubMedCrossRef Schlagbauer-Wadl H, Jansen B, Muller M, Polterauer P, Wolff K, Eichler HG, et al. Influence of MUC18/MCAM/CD146 expression on human melanoma growth and metastasis in SCID mice. Int J Cancer. 1999;81(6):951–5.PubMedCrossRef
20.
Zurück zum Zitat Zeng GF, Cai SX, Wu GJ. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells. BMC Cancer. 2011;11:113.PubMedCentralPubMedCrossRef Zeng GF, Cai SX, Wu GJ. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells. BMC Cancer. 2011;11:113.PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Zeng Q, Li W, Lu D, Wu Z, Duan H, Luo Y, et al. CD146, an epithelial–mesenchymal transition inducer, is associated with triple-negative breast cancer. Proc Natl Acad Sci USA. 2012;109(4):1127–32.PubMedCrossRef Zeng Q, Li W, Lu D, Wu Z, Duan H, Luo Y, et al. CD146, an epithelial–mesenchymal transition inducer, is associated with triple-negative breast cancer. Proc Natl Acad Sci USA. 2012;109(4):1127–32.PubMedCrossRef
22.
Zurück zum Zitat Imbert AM, Garulli C, Choquet E, Koubi M, Aurrand-Lions M, Chabannon C. CD146 expression in human breast cancer cell lines induces phenotypic and functional changes observed in epithelial–mesenchymal transition. PLoS ONE. 2012;7(8):e43752.PubMedCentralPubMedCrossRef Imbert AM, Garulli C, Choquet E, Koubi M, Aurrand-Lions M, Chabannon C. CD146 expression in human breast cancer cell lines induces phenotypic and functional changes observed in epithelial–mesenchymal transition. PLoS ONE. 2012;7(8):e43752.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Kristiansen G, Yu Y, Schluns K, Sers C, Dietel M, Petesen I. Expression of the cell adhesion molecule CD146/MCAM in non-small cell lung cancer. Anal Cell Pathol. 2003;25:77–81.PubMed Kristiansen G, Yu Y, Schluns K, Sers C, Dietel M, Petesen I. Expression of the cell adhesion molecule CD146/MCAM in non-small cell lung cancer. Anal Cell Pathol. 2003;25:77–81.PubMed
24.
Zurück zum Zitat Oka S, Uramoto H, Chikaishi Y, Tanaka F. The expression of CD146 predicts a poor overall survival in patients with adenocarcinoma of the lung. Anticancer Res. 2012;32(3):861–4.PubMed Oka S, Uramoto H, Chikaishi Y, Tanaka F. The expression of CD146 predicts a poor overall survival in patients with adenocarcinoma of the lung. Anticancer Res. 2012;32(3):861–4.PubMed
25.
Zurück zum Zitat Travis WD, Brambilla E, Mueller-Hermelink HK, Harris CC. World health organization classifications of tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. 2nd ed. Lyon: IARC Press; 2004. Travis WD, Brambilla E, Mueller-Hermelink HK, Harris CC. World health organization classifications of tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. 2nd ed. Lyon: IARC Press; 2004.
26.
Zurück zum Zitat Tischler V, Pfeifer M, Hausladen S, Schrimer U, Bonde AK, Kristiansen G, et al. L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer. Mol Cancer. 2011;10:127.PubMedCentralPubMedCrossRef Tischler V, Pfeifer M, Hausladen S, Schrimer U, Bonde AK, Kristiansen G, et al. L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer. Mol Cancer. 2011;10:127.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Wu Z, Wu Z, Li J, Yang X, Wang Y, Yu Y, et al. MCAM is a novel metastasis marker and regulates spreading, apoptosis and invasion of ovarian cancer cells. Tumour Biol. 2012;33(5):1619–28.PubMedCentralPubMedCrossRef Wu Z, Wu Z, Li J, Yang X, Wang Y, Yu Y, et al. MCAM is a novel metastasis marker and regulates spreading, apoptosis and invasion of ovarian cancer cells. Tumour Biol. 2012;33(5):1619–28.PubMedCentralPubMedCrossRef
28.
29.
Zurück zum Zitat Zigler M, Villares GJ, Dobroff AS, Wang H, Huang L, Braeuer RR, et al. Expression of Id-1 is regulated by MCAM/MUC18: a missing link in melanoma progression. Cancer Res. 2011;71(10):3494–504.PubMedCentralPubMedCrossRef Zigler M, Villares GJ, Dobroff AS, Wang H, Huang L, Braeuer RR, et al. Expression of Id-1 is regulated by MCAM/MUC18: a missing link in melanoma progression. Cancer Res. 2011;71(10):3494–504.PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Zeng G, Cai S, Liu Y, Wu GJ. METCAM/MUC18 augments migration, invasion, and tumorigenicity of human breast cancer SK-BR-3 cells. Gene. 2012;492(1):229–38.PubMedCrossRef Zeng G, Cai S, Liu Y, Wu GJ. METCAM/MUC18 augments migration, invasion, and tumorigenicity of human breast cancer SK-BR-3 cells. Gene. 2012;492(1):229–38.PubMedCrossRef
31.
Zurück zum Zitat Chen W, Zhang HL, Jiang YG, Li JH, Liu BL, Sun MY. Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC-M cell. J Oral Pathol Med. 2009;38(2):198–205.PubMedCrossRef Chen W, Zhang HL, Jiang YG, Li JH, Liu BL, Sun MY. Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC-M cell. J Oral Pathol Med. 2009;38(2):198–205.PubMedCrossRef
32.
Zurück zum Zitat Leslie MC, Zhao YJ, Lachman LB, Hwu P, Wu GJ, Bar-Eli M. Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastasis. Gene Ther. 2007;14(4):316–23.PubMedCrossRef Leslie MC, Zhao YJ, Lachman LB, Hwu P, Wu GJ, Bar-Eli M. Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastasis. Gene Ther. 2007;14(4):316–23.PubMedCrossRef
Metadaten
Titel
MCAM expression is associated with poor prognosis in non-small cell lung cancer
verfasst von
X. Zhang
Z. Wang
Y. Kang
X. Li
X. Ma
L. Ma
Publikationsdatum
01.02.2014
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 2/2014
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1057-6

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