만성피부궤양과 편평세포암의 MMP-7과 MMP-13 발현에 관한 면역조직화학적 연구 = Immunohistochemical Expression of MMP-7 and MMP-13 in Chronic Cutaneous Ulcers and Squamous Cell Carcinomas만성피부궤양과 편평세포암의 MMP-7과 MMP-13 발현에 관한 면역조직화학적 연구

다국어 초록 (Multilingual Abstract)

Background: The risk of squamous cell carcinoma (SCC) is significantly increased in chronic cutaneous ulcers. Moreover, if the proliferating epithelium of the ulcer margin shows pseudoepitheliomatous hyperplasia, it can be very difficult to discriminate between the two diseases. Enzymes such as matrix metalloproteinases (MMPs) are thought to be implicated at all stages of tumorigenesis. Objective: We investigated the expression patterns of epithelial MMP-7 and MMP-13 in chronic ulcers and SCCs by an immunohistochemical technique and the usefulness in differentiating these two entities. Methods: Formalin-fixed and paraffin-embedded tissues obtained from 16 chronic ulcers and 12 SCC patients were studied using an immunohistochemical staining method for MMP-7 and MMP-13. Results: MMP-7 and MMP-13 were expressed by the malignant tumor cells of 4 (33.3%) and 9 SCC samples (75%), respectively, while they were absent from the proliferating epithelium of chronic ulcers. Conclusion: Our results suggest that epithelial expression of both MMP-7 and MMP-13 have a specificity in differentiating the benign epithelial proliferation of chronic ulcer from malignant tumor cells, but MMP-13 seems to be a more sensitive and useful marker due to the lower sensitivity of MMP-7 in SCCs. (Korean J Dermatol 2006; 44(11):1284~1289)

참고문헌 (Reference)

1 "Wound healing" Mosby 2207-2218, 2003

2 "Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells" 70 : 486-497, 2002

3 "Stromelysin-1 activation correlates with invasiveness in squamous cell carcinoma" 118 : 759-766, 2002

4 "Role of matrix metalloproteinases(MMPs)in colorectal cancer" 23 : 101-117, 2004

5 "Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1" 114 : 111-118, 2001

6 "New functions for the matrix metalloproteinases in cancer progression" 2 : 161-174, 2002

7 "Mechanisms of cutaneous wound repair" McGraw-Hill 236-246, 2003

8 "Matrix metalloproteinases in tumor progression:focus on basal and squamous cell skin cancer" 12 : 109-125, 2003

9 "Matrix metalloproteinases in cancer:prognostic markers and therapeutic targets" 99 : 157-166, 2002

10 "Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development" 89 : 1817-1821, 2003

11 "Matrix metalloproteinases and the development of cancer" 3 : 895-904, 1996

12 "Matrix metalloproteinase-7 mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity" 61 : 557-581, 2001

13 "Matrix metalloproteinase-19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation" 103 : 709-716, 2003

14 "Matrisian LM. Matrix metalloproteinases: they're not just for matrix anymore!" 13 : 534-540, 2001

15 "Matrilysin(PUMP)correlates with dermal invasion during appendageal development and cutaneous neoplasia" 103 : 482-487, 1994

16 "Matrilysin in epithelial repair and defense" 120 : 36-41, 2001

17 "Matrilysin expression and function in airway epithelium" 102 : 1321-1331, 1998

18 "Inflammation and cancer" 420 : 860-867, 2002

19 "Human papillomavirus in venous ulcers with and without squamous cell carcinoma" 292 : 275-278, 2000

20 "Human collagenase-3 is expressed in malignant squamous epithelium of the skin" 109 : 225-231, 1997

21 "Expression of matirix metalloproteinase(MMP)-7 and MMP-13 and loss of MMP-19 and p16 are associated with malignant progression in chronic wounds" 152 : 720-726, 2005

22 "Expression of collagenase-3(matrix metalloproteinase-13)in squamous cell carcinomas of the head and neck" 151 : 499-508, 1997

23 "Epilysin(MMP-28)expression is associated with cell proliferation during epithelial repair" 119 : 12-21, 2002

24 "Enhanced expression of matrilysin,collagenase,and stromelysin-1 in gastrointestinal ulcer" 148 : 519-526, 1996

25 "Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds" 33 : 355-364, 2002

26 "Distinct populations of stromal cells express collagenase-3 in chronic ulcers but not in normally healing wounds" 109 : 96-101, 1997

27 "A comparison of expression of MMP-3 TIMP-1 and apoptosis in keratoacanthoma and squamous cell carninoma" 43 : 489-495, 2005