Skip to main content
Top
Published in: Medical Oncology 1/2013

01-03-2013 | Original Paper

Clinicopathologic significance of β-catenin and matrix metalloproteinase-2 expression in non-small cell lung cancer

Authors: Guang-Hu Li, Yong-Sheng Cui, Qi-Yu Wu, Xiong-Ji Zhang, Yu-Fei Gao

Published in: Medical Oncology | Issue 1/2013

Login to get access

Abstract

The purpose of this study was to analyze β-catenin and matrix metalloproteinase-2 (MMP-2) expression in non-small cell lung cancer (NSCLC) and to investigate the association between their expression and clinicopathologic characteristics of NSCLC patients. Immunohistochemistry was performed to examine β-catenin and MMP-2 protein expression in 39 resected NSCLC samples and 8 adjacent normal lung tissues. Statistical analysis with SPSS13.0 software was performed to investigate the association between β-catenin and MMP-2 expression and clinicopathologic features of the patients. Expression of cytosolic β-catenin in NSCLC tissue was significantly higher than that in normal tissues (P < 0.001). In addition, cytosolic protein expression of β-catenin in lung squamous cell carcinoma was significantly elevated compared to that in lung adenocarcinoma (P = 0.02). However, cell membrane protein expression of β-catenin in squamous cell carcinoma was lower than that in adenocarcinoma (P = 0.041). Cytosolic MMP-2 protein expression in NSCLC samples was significantly higher than that in normal tissues (P = 0.002). MMP-2 expression in N 1–2 NSCLC patients was significantly increased relative to N 0 patients (P = 0.019). However, statistical analysis showed no correlation between β-catenin and MMP-2 expression in NSCLC samples. Collectively, our results show that cytosolic protein expression of β-catenin in NSCLC samples is increased relative to normal lung tissues. Also, expression of β-catenin is significantly elevated in squamous cell carcinoma compared to that in lung adenocarcinoma subtypes. Additionally, MMP-2 expression in N 1–2 NSCLC tissues is higher than that in N 0 lung tissue. There is no correlation between β-catenin and MMP-2 expression in NSCLC, and our study suggests that evaluation of β-catenin and MMP-2 expression may have potential in diagnosis and progression in patients with NSCLC.
Literature
1.
go back to reference Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–94.PubMed Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–94.PubMed
2.
3.
go back to reference Kashima T, Kawaguchi J, Takeshita S, Kuroda M, Takanashi M, Horiuchi H, et al. Anomalous cadherin expression in osteosarcoma. Possible relationships to metastasis and morphogenesis. Am J Pathol. 1999;155(5):1549–55.PubMedCrossRef Kashima T, Kawaguchi J, Takeshita S, Kuroda M, Takanashi M, Horiuchi H, et al. Anomalous cadherin expression in osteosarcoma. Possible relationships to metastasis and morphogenesis. Am J Pathol. 1999;155(5):1549–55.PubMedCrossRef
4.
go back to reference Pagaki E, Patsouris E, Gonidi M, Athanassiadou AM, Maurikakis M, Athanassiades P, et al. The value of E-cadherin/beta-catenin expression in imprints of NCSLC: relationship with clinicopathological factors. Diagn Cytopathol. 2010;38(6):419–24.PubMed Pagaki E, Patsouris E, Gonidi M, Athanassiadou AM, Maurikakis M, Athanassiades P, et al. The value of E-cadherin/beta-catenin expression in imprints of NCSLC: relationship with clinicopathological factors. Diagn Cytopathol. 2010;38(6):419–24.PubMed
5.
go back to reference Lu Z, Lu N, Li C, Li F, Zhao K, Lin B, et al. Oroxylin A inhibits matrix metalloproteinase-2/9 expression and activation by up-regulating tissue inhibitor of metalloproteinase-2 and suppressing the ERK1/2 signaling pathway. Toxicol Lett. 2012;209(3):211–20.PubMedCrossRef Lu Z, Lu N, Li C, Li F, Zhao K, Lin B, et al. Oroxylin A inhibits matrix metalloproteinase-2/9 expression and activation by up-regulating tissue inhibitor of metalloproteinase-2 and suppressing the ERK1/2 signaling pathway. Toxicol Lett. 2012;209(3):211–20.PubMedCrossRef
6.
go back to reference Sims JD, McCready J, Jay DG. Extracellular heat shock protein (Hsp)70 and Hsp90alpha assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS ONE. 2011;6(4):e18848.PubMedCrossRef Sims JD, McCready J, Jay DG. Extracellular heat shock protein (Hsp)70 and Hsp90alpha assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS ONE. 2011;6(4):e18848.PubMedCrossRef
7.
go back to reference Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future. J Clin Oncol. 2005;23(14):3175–85.PubMedCrossRef Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future. J Clin Oncol. 2005;23(14):3175–85.PubMedCrossRef
8.
go back to reference Takahashi M, Tsunoda T, Seiki M, Nakamura Y, Furukawa Y. Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene. 2002;21(38):5861–7.PubMedCrossRef Takahashi M, Tsunoda T, Seiki M, Nakamura Y, Furukawa Y. Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene. 2002;21(38):5861–7.PubMedCrossRef
9.
go back to reference He B, Barg RN, You L, Xu Z, Reguart N, Mikami I, et al. Wnt signaling in stem cells and non-small-cell lung cancer. Clin Lung Cancer. 2005;7(1):54–60.PubMedCrossRef He B, Barg RN, You L, Xu Z, Reguart N, Mikami I, et al. Wnt signaling in stem cells and non-small-cell lung cancer. Clin Lung Cancer. 2005;7(1):54–60.PubMedCrossRef
10.
go back to reference Lai SL, Chien AJ, Moon RT. Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis. Cell Res. 2009;19(5):532–45.PubMedCrossRef Lai SL, Chien AJ, Moon RT. Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis. Cell Res. 2009;19(5):532–45.PubMedCrossRef
11.
go back to reference Mukherjee N, Bhattacharya N, Alam N, Roy A, Roychoudhury S, Panda CK. Subtype-specific alterations of the Wnt signaling pathway in breast cancer: clinical and prognostic significance. Cancer Sci. 2012;103(2):210–20.PubMedCrossRef Mukherjee N, Bhattacharya N, Alam N, Roy A, Roychoudhury S, Panda CK. Subtype-specific alterations of the Wnt signaling pathway in breast cancer: clinical and prognostic significance. Cancer Sci. 2012;103(2):210–20.PubMedCrossRef
12.
go back to reference Retera JM, Leers MP, Sulzer MA, Theunissen PH. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study. J Clin Pathol. 1998;51(12):891–4.PubMedCrossRef Retera JM, Leers MP, Sulzer MA, Theunissen PH. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study. J Clin Pathol. 1998;51(12):891–4.PubMedCrossRef
13.
go back to reference Zang D, Li X, Zhang L. 14–3-3zeta Overexpression and abnormal beta-catenin expression are associated with poor differentiation and progression in stage I non-small cell lung cancer. Clin Exp Med. 2010;10(4):221–8.PubMedCrossRef Zang D, Li X, Zhang L. 14–3-3zeta Overexpression and abnormal beta-catenin expression are associated with poor differentiation and progression in stage I non-small cell lung cancer. Clin Exp Med. 2010;10(4):221–8.PubMedCrossRef
14.
go back to reference Kim YT, Choi EK, Kim JW, Kim DK, Kim SH, Yang WI. Expression of E-cadherin and alpha-, beta-, gamma-catenin proteins in endometrial carcinoma. Yonsei Med J. 2002;43(6):701–11.PubMed Kim YT, Choi EK, Kim JW, Kim DK, Kim SH, Yang WI. Expression of E-cadherin and alpha-, beta-, gamma-catenin proteins in endometrial carcinoma. Yonsei Med J. 2002;43(6):701–11.PubMed
15.
go back to reference Chelidonis G, Kavantzas N, Patsouris E, Pagaki E, Athanasiadou AM, Agrogiannis G, et al. DNA ploidy, E-cadherin, beta-catenin expression and their clinicopathologic significance in imprints of non-small cell lung cancer. Anal Quant Cytol Histol. 2009;31(5):332–9.PubMed Chelidonis G, Kavantzas N, Patsouris E, Pagaki E, Athanasiadou AM, Agrogiannis G, et al. DNA ploidy, E-cadherin, beta-catenin expression and their clinicopathologic significance in imprints of non-small cell lung cancer. Anal Quant Cytol Histol. 2009;31(5):332–9.PubMed
16.
go back to reference Maeda D, Shibahara J, Sakuma T, Isobe M, Teshima S, Mori M, et al. beta-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors. Am J Surg Pathol. 2011;35(10):1429–40.PubMedCrossRef Maeda D, Shibahara J, Sakuma T, Isobe M, Teshima S, Mori M, et al. beta-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors. Am J Surg Pathol. 2011;35(10):1429–40.PubMedCrossRef
17.
go back to reference Xu HT, Wang L, Lin D, Liu Y, Liu N, Yuan XM, et al. Abnormal beta-catenin and reduced axin expression are associated with poor differentiation and progression in non-small cell lung cancer. Am J Clin Pathol. 2006;125(4):534–41.PubMed Xu HT, Wang L, Lin D, Liu Y, Liu N, Yuan XM, et al. Abnormal beta-catenin and reduced axin expression are associated with poor differentiation and progression in non-small cell lung cancer. Am J Clin Pathol. 2006;125(4):534–41.PubMed
18.
go back to reference Chiu CG, Chan SK, Fang ZA, Masoudi H, Wood-Baker R, Jones SJ et al. Beta-catenin expression is prognostic of improved non-small cell lung cancer survival. Am J Surg. 2012;203(5):654–9. Chiu CG, Chan SK, Fang ZA, Masoudi H, Wood-Baker R, Jones SJ et al. Beta-catenin expression is prognostic of improved non-small cell lung cancer survival. Am J Surg. 2012;203(5):654–9.
19.
go back to reference Stetler-Stevenson WG. Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix. Am J Pathol. 1996;148(5):1345–50.PubMed Stetler-Stevenson WG. Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix. Am J Pathol. 1996;148(5):1345–50.PubMed
20.
go back to reference Hida Y, Hamada JI. Differential expressions of matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs and their endogenous inhibitors among histologic subtypes of lung cancers. Anticancer Agents Med Chem. 2012;12(7):744–52. Hida Y, Hamada JI. Differential expressions of matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs and their endogenous inhibitors among histologic subtypes of lung cancers. Anticancer Agents Med Chem. 2012;12(7):744–52.
21.
go back to reference Shao W, Wang W, Xiong XG, Cao C, Yan TD, Chen G, et al. Prognostic impact of MMP-2 and MMP-9 expression in pathologic stage IA non-small cell lung cancer. J Surg Oncol. 2011;104(7):841–6.PubMedCrossRef Shao W, Wang W, Xiong XG, Cao C, Yan TD, Chen G, et al. Prognostic impact of MMP-2 and MMP-9 expression in pathologic stage IA non-small cell lung cancer. J Surg Oncol. 2011;104(7):841–6.PubMedCrossRef
22.
go back to reference Xu X, Sun PL, Li JZ, Jheon S, Lee CT, Chung JH. Aberrant Wnt1/beta-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery. J Thorac Oncol. 2011;6(4):716–24.PubMedCrossRef Xu X, Sun PL, Li JZ, Jheon S, Lee CT, Chung JH. Aberrant Wnt1/beta-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery. J Thorac Oncol. 2011;6(4):716–24.PubMedCrossRef
Metadata
Title
Clinicopathologic significance of β-catenin and matrix metalloproteinase-2 expression in non-small cell lung cancer
Authors
Guang-Hu Li
Yong-Sheng Cui
Qi-Yu Wu
Xiong-Ji Zhang
Yu-Fei Gao
Publication date
01-03-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-012-0437-z

Other articles of this Issue 1/2013

Medical Oncology 1/2013 Go to the issue