Browse > Article

The Relationship between Expression of EGFR, MMP-9, and C-erbB-2 and Survival Time in Resected Non-Small Cell Lung Cancer  

Lee, Seung Heon (Department of Internal Medicine, College of Medicine, Korea University)
Jung, Jin Yong (Department of Internal Medicine, College of Medicine, Korea University)
Lee, Kyoung Ju (Department of Internal Medicine, College of Medicine, Korea University)
Lee, Seung Hyeun (Department of Internal Medicine, College of Medicine, Korea University)
Kim, Se Joong (Department of Internal Medicine, College of Medicine, Korea University)
Ha, Eun Sil (Department of Internal Medicine, College of Medicine, Korea University)
Kim, Jeong-Ha (Department of Internal Medicine, College of Medicine, Korea University)
Lee, Eun Joo (Department of Internal Medicine, College of Medicine, Korea University)
Hur, Gyu Young (Department of Internal Medicine, College of Medicine, Korea University)
Jung, Ki Hwan (Department of Internal Medicine, College of Medicine, Korea University)
Jung, Hye Cheol (Department of Internal Medicine, College of Medicine, Korea University)
Lee, Sung Yong (Department of Internal Medicine, College of Medicine, Korea University)
Lee, Sang Yeub (Department of Internal Medicine, College of Medicine, Korea University)
Kim, Je Hyeong (Department of Internal Medicine, College of Medicine, Korea University)
Shin, Chol (Department of Internal Medicine, College of Medicine, Korea University)
Shim, Jae Jeong (Department of Internal Medicine, College of Medicine, Korea University)
In, Kwang Ho (Department of Internal Medicine, College of Medicine, Korea University)
Kang, Kyung Ho (Department of Internal Medicine, College of Medicine, Korea University)
Yoo, Se Hwa (Department of Internal Medicine, College of Medicine, Korea University)
Kim, Chul Hwan (Department of Pathology, College of Medicine, Korea University)
Publication Information
Tuberculosis and Respiratory Diseases / v.59, no.3, 2005 , pp. 286-297 More about this Journal
Abstract
Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.
Keywords
Non-Small Cell Lung Cancer; EGFR; MMP-9; C-erbB-2;
Citations & Related Records

Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Pinto CA, Carvalho PE, Antonangelo L, Garripo A, da Silva AG, Soares F, et al. Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adeno-carcinoma of the lung. Clin Cancer Res 2003;9:3098-104
2 Tsai CM, Chang KT, Perng RP, Mitsudomi T, Chen MH, Kadoyama C, et al. Correlation of intrinsic chemoresistance of non-small cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. J Natl Cancer Inst 1993;85:897-901   DOI   ScienceOn
3 Akita K, Inagaki H, Sato S, Niimi T, Maeda H, Ninomiya S, et al. $P185^{HER}-^{2/neu}$ and $P21^{CIP1/WAF1$ expression in primary tumors and lymph node metastases in Non-small lung cance. Jpn J Cancer Res 2002;93:1007-11
4 Pfeiffer P, Calussen PP, Andersen K, Rose C. Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185 HER-2 patients with systematically untreated non-small cell lung cancer: an immunohistochemical study on cryosections. Br J Cancer 1996;74;86-91   ScienceOn
5 Kern JA, Schwarts DA, Nordberg JE, Weiner DB, Greene MI, Torney L, et al. P185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res 1990;50:5184-7
6 Diez M, Pollan M, Maestro M, Torres A, Ortega D, Gomez A, et al. Prediction of recurrence by quantification of p 185neu protein in non-small cell lung cancer tissue. Br J Cancer 1997;75:684-9   ScienceOn
7 Rosenthal EL, Johnson TM, Allen ED, Apel IJ, Punturieri A, Weiss SJ. Role of the plasminogen activator and matrix metalloproteinase systems in epidermal growth factor and scatter factor stimulated invasion of carcinoma cells. Cancer Res 1998;58: 5221-30
8 Llorens A, Rodrigo I, Lopez-Barcons L, Gonzalez-Gaꠀ rrigues M, Lozano E, Vinyals A, et al. Down regulation of E-cadherin in mouse skin carcinoma cells enhance a migratory and invasive phenotype linked to matrix metalloproteinase-9 gelatinase expression. Lab Invest 1998;78:1131-42
9 Pastorino U, Andreola S, Tagliabue E, Pezzella F, Incarbone M, Sozzi G, et al. Immunocytochemical markers in stage I lung cancer: relevance to prognosis. J Clin Oncol 1997;15:2858-65
10 Kim HR, Jeong ET. Expression of EGFR in non-small cell lung cancer and effects on survival. Tuberc Respir Dis 1997;44:1285-95
11 Selvaggi G, Novello S, Torri V, Leonardo E, de Giuli P, Borasio P, et al. Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer. Ann Oncol 2004;15;28-32   DOI   ScienceOn
12 Sienel W, Hellers J, Morresi-Hauf A, Lichtinghagen R, Mutschler W, Jochum M, et al. Prognostic impact of matrix metalloproteinase-9 in operable non-small cell lung cancer. Int J Cancer 2003;103:647-51   DOI   ScienceOn
13 Schneider PM, Praeuer HW, Stoeltzing O, Boehm J, Manning J, Metzger R, et al. Multiple molecular marker testing(p-53, C-ki-ras, C-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer. Br J Cancer 2000;83: 473-9   DOI   ScienceOn
14 Brown PD, Bloxidge RE, Stuart NS, Gatter KC, Camichael J. Association between expression of 72-kilodalton gelatinase and tumour spread in non-small cell lung cancer. J Natl Cancer Inst 1993; 85:574-8   DOI   ScienceOn
15 Cox G, Jones JL, Andi A, Walker DA, O'Byrne KJ. A biological staging model for operable non-small cell lung cancer. Thorax 2001;56:561-6   DOI   ScienceOn
16 Curran S, Murray GI. Matrix metalloproteinases: moꠀ lecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 2000;36:1621-30   DOI   ScienceOn
17 O-charoenrat P, Rhys-Evens P, Modjtahedi H, Court W, Box G, Eccles S. Overexpression of epidermal growth factor receptor in human head and neck squamous carcinoma cell lines correlates with matrix metalloproteinase-9 expression and in vitro invsion. Int J Cancer 2000;86:307-17   DOI   ScienceOn
18 Cox G, Jones JL, O'Byrne KJ. MMP-9 and the epidermal growth factor receptor signal pathway in operable non-small cell lung cancer. Clin Cancer Res 2000;6:2349-55
19 Ciardiello F, Caputo R, Bianco R, Damiano V, Fontaꠀ nini G, Cuccato S, et al. Inhibition of growth factor production and angiogenesis in human cander cells by ZD1839(Irresa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res 2001;7:1459-65
20 Westermarck J, Kahari VM. Regulation of matrix meꠀ talloproteinase expression in tumor invasion. FASEB J 1999;13:781-92
21 Osann KE, Ernster VL, Mustacchi P. Chapter 45. Epidemiology of lung cancer. In: Murray JF, Nadel JA, editors. Textbook of respiratory medicine. 3rd ed. Philadelphia: W.B. Sanuders, company; 2001. p. 1395- 407
22 O'Byrne KJ, Cox G, Swinson D, Richardson D, Edwards JG, Lolljee J, et al. Towards a biological staging model for operable non-small cell lung cancer. Lung Cancer 2001;34:S83-9   DOI   ScienceOn
23 Perez-Soler R. HER1/EGFR targeting: refining the strategy. Oncologist 2004;9:58-67   DOI   ScienceOn