title: Clinical relevance of serum levels of matrix metallopeptidase-2, and tissue inhibitor of metalloproteinase-1 and -2 in patients with malignant melanoma.
abstract: The interaction and/or balance between matrix metallopeptidase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP)-2 in vivo may play important roles in the process of tumor growth, invasion and metastasis of malignant melanoma. In this study, we investigated the serum levels and immunohistochemical expression of MMP-2, TIMP-1 and TIMP-2 in patients with melanoma and analyzed the correlation with clinicopathological parameters. The level of serum MMP-2 in patients was significantly higher than that of the control. Moreover, the level of MMP-2 was significantly higher than that of the control in patients who were: (i) female; (ii) pT1 and pT4; (iii) with and without lymph node (LN) metastasis; (iv) in stage I and stage IV; (v) with and without recurrence; and (v) alive and dead. The level of serum TIMP-1 in patients with melanoma was significantly higher than that of the control. Among melanoma patients, the level of TIMP-1 with pT4 was significantly higher for patients who were: (i) pT1 and pT3; (ii) with LN metastasis (vs those without); (iii) in stage IV (vs those in stages I, II and III); and (iv) dead (vs those alive). The level of serum TIMP-2 in patients with melanoma was not different from the control. However, the level of TIMP-2 in patients with pT4 was significantly higher than for patients who were: (i) pT1, pT3 and control; (ii) with LN metastasis (vs those without metastasis and control); (iii) with stage IV (vs those in stages I and II and control); (iv) in recurrence (vs control); and (v) dead (vs those alive and control). These results suggest that increased serum levels of TIMP-1 and TIMP-2 reflected the extent of metastatic melanoma lesions, and that serum levels of TIMP-1 may be a new useful marker for melanoma progression.
authors.affiliation: Department of Dermatology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan. derma-yoshino@m2.dion.ne.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshino
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kageshita
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Minako
authors.initials: M
authors.lastname: Funakubo
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2