title: A prognostic index in skin melanoma through the combination of matrix metalloproteinase-2, Ki67, and p53.
abstract: The objective of this immunohistochemical study was to explore the roles of Ki67 and p53 in conjunction with matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 in a series of 157 cases of skin melanomas. Elevated Ki67 expression and positive staining for p53 correlated to the propensity to metastasize (P = .016) and to declined disease-specific survival, as well as to shortened recurrence-free survival. In patients with a high immunoreaction for Ki67, the 10-year disease-specific survival was 39% compared with 73% in patients with a low Ki67 expression (P = .03). In cases with a positive p53 expression in melanoma cells, the 10-year disease-specific survival was 59% compared with 76% in patients with a negative immunoreaction for p53 (P = .005). Overexpression of the matrix metalloproteinase 2 protein in conjunction with overexpression of Ki67 characterized melanomas with high metastatic potential and was associated with declined survival with a 10-year disease-specific survival of 33% compared with 85% in the cases with low matrix metalloproteinase-2 and low Ki-67 levels (P = .002). Similarly, in cases with overexpression of matrix metalloproteinase-2 and a positive immunoreaction for p53, the 10-year disease-specific survival was only 42% compared with 80% in patients with matrix metalloproteinase-2 less than 20% and a negative immunostaining for p53 (P < .001). The presence of all 3 adverse prognostic factors was prognostically more significant than any marker alone with a 10-year survival of only 28%. This combination of determining matrix metalloproteinase 2, Ki67, and p53 immunoreactive proteins could be beneficial in the selection of high-risk melanoma patients for future adjuvant trials.
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital, OYS 90029, Oulu, Finland. anne.vaisanen@ppshp.fi
authors.forename: Anne
authors.initials: A
authors.lastname: Väisänen
authors.forename: Paula
authors.initials: P
authors.lastname: Kuvaja
authors.forename: Matti
authors.initials: M
authors.lastname: Kallioinen
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2