제1기 비소세포폐암 환자의 수술적 절제 후 Matrix Metalloproteinase-2 활성도에 따른 재발 및 예후 = Activity of Matrix Metalloproteinase-2 and its Significance after Resection of Stage I Non-small Cell Lung Cancer

다국어 초록 (Multilingual Abstract)

Background: Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p＜0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p＜0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

국문 초록 (Abstract)

배경: 기질금속단백분해효소-2 (MMP-2)는 기저막과 세포 외 기질의 분해에 작용하여 악성종양의 국소침윤 및 원격전이에 중요한 역할을 담당한다. 본 연구는 수술적인 절제를 시행 받은 제1기 비소세포폐암에서 MMP-2의 활성도를 측정하고 예후인자로서의 의미를 분석하고자 하였다. 대상 및 방법: 수술 전 방사선 또는 항암제 요법을 시행하지 않은 병리학적 제1기 비소세포폐암 환자 34명을 대상으로 하였다. 폐엽 절제 조직에서 종양 조직과 비종양 조직의 단백질을 각각 추출하여 젤라틴-기질-단백분해효소 분석법을 시행하였다. 결과: MMP-2 활성도는 비종양 조직보다 종양 조직에서 높았다. 종양 조직, 비종양 조직 모두에서 비재발군에 비해 재발군의 MMP-2 활성도가 높았으나 비종양 조직에서의 차이가 통계적 유의성이 있었다(p＜0.01). 생존율 분석에서도 MMP-2 활성도가 높을 경우 불량한 생존을 보였으며 역시 비종양 조직에서 통계적인 의미가 있었다(p＜0.01). 결론: 제1기 비소세포폐암 환자의 절제 폐엽 조직 중 비종양 조직에서의 MMP-2 활성도는 재발 및 생존과 연관성이 있으며 예후 인자로서의 가능성이 있다.

참고문헌 (Reference)

1 "type IV collagenases in colorectal cancer" 190-6, 1996

2 "an imbalance of positive and negative"

3 "a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family" 87 : 1990

4 "Type IV collagenase in invasive tumors" 209-18, 1993

5 "The role of matrix metalloproteases and their inhibitors in tumour invasion" 2062-72, 1994

6 "The regulation of neovascularization by matrix metalloproteinases & their inhibitors" 15 : 180-, 1997

7 "Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors" 81 : 69-77, 1994

8 "Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma.A clinicopathologic study" 70 : 2747-53, 1992

9 "Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer" Clin Cancer Res 6 : 3944-8, 2000

10 "Overexpression level of stromelysin 3 is related to the lymph node involvement in non-small cell lung cancer" Clin Cancer Res 6 : 1086-92, 2000

11 "Mechanisms controlling the transcription of matrix metalloproteinase genes in normal and neoplastic cells" 49 : 20-37, 1996

12 "Matrix metalloproteinases" 274 : 21491-, 1999

13 "Matrix metalloproteinase 9 and the epidermal growth factor signal pathway in operable non-small cell lung cancer" Clin Cancer Res 6 : 2349-55, 2000

14 "Identification of the 72-kDa gelatinase/type IV collagenase in preparations of laminin and Matrigel" 15 : 1048-2 9 51, 1993

15 "Extracellular matrix 6:role of matrix metalloproteinases in tumor invasion and metastasis" 7 : 1434-41, 1993

16 "Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice" 53 : 417-22, 1993

17 "Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential" 52 : 4942-7, 1992

18 "Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer" 17 : 1802-8, 1999

19 "Differential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer" 190 : 150-6, 2000

20 "Detection of mRNAs encoding collagenase I and stromelysin 2 in carcinomas of the head and neck by In situ hybridization" 11 : 76-83, 1991

21 "Characteristics of a 95-kDa matrix metalloproteinase produced by mammary carcinoma cells" 30 : 1449-56, 1991

22 "Changing views of the role of matrix metalloproteinases in metastasis" 89 : 1279-, 1997