title: Expression of gelatinases (MMP-2, MMP-9) and gelatinase activator (MMP-14) in actinic keratosis and in in situ and invasive squamous cell carcinoma.
abstract: Given the established role of matrix metalloproteinases (MMPs) in physiological processes in the skin, we investigated the expression of MMP-2, MMP-9, and MMP-14 to evaluate their role in the grading and development of atypical epithelial lesions. Immunohistochemistry was performed using antibodies against these MMPs in actinic keratosis (AK; n = 24), squamous cell carcinoma (SCC) in situ (SCCIS; n = 27), SCC well differentiated (SCCWD; n = 28), and SCC moderately to poorly differentiated (SCCMPD; n = 20). Tumoral and stromal expression was assessed by intensity (SI) and percentage positivity (PC). The mean of the total score, calculated by adding intensity and percentage positivity, was used for statistical analyses. In AK, SCCIS, SCCWD, and SCCMPD, mean tumoral MMP-2 expression was 3.33, 4.07, 4.46, and 3.40, respectively (P = NS for all) and stromal expression was 1.42, 3.26, 3.07, and 1.55 respectively (P < 0.05 for AK vs. SCCIS/SCCWD and SCCMPD vs. SCCIS/SCCWD); mean tumoral MMP-9 expression was 4.33, 4.11, 4.46, and 3.35, respectively, and stromal expression was 4.29, 4.41, 4.75, and 4.60, respectively (P = NS for all) and, mean tumoral MMP-14 expression was 1.58, 2.41, 0.32, and 0.35, respectively (P < 0.05 AK vs. SCCWD and SCCIS vs. SCCWD/SCCMPD) and stromal expression was 3.04, 3.52, 0.46, and 0.60, respectively (P < 0.05 for AK vs. SCCWD/SCCMPD). Only MMP-14 showed a statistically significant linear trend with decreasing values for tumoral and stromal expression with invasion suggesting that it might be of use as a prognosticator. Enhanced stromal MMP-2 expression in SCCIS and SCCWD relative to AK suggests that it may be of relevance to disease progression.
authors.affiliation: Pathology Department and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Marier
authors.initials: M
authors.lastname: Hernández-Pérez
authors.forename: Mohamad
authors.initials: M
authors.lastname: El-hajahmad
authors.forename: Joseph
authors.initials: J
authors.lastname: Massaro
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
mesh_terms: D000704:Analysis of Variance; D001706:Biopsy; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D018450:Disease Progression; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000201:enzymology* / Q000473:pathology; D016014:Linear Models; D053511:Matrix Metalloproteinase 14 / Q000032:analysis*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14