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Expression of Gelatinases (MMP-2, MMP-9) and Gelatinase Activator (MMP-14) in Actinic Keratosis and in In Situ and Invasive Squamous Cell Carcinoma

Hernández-Pérez, Marier MD*; El-hajahmad, Mohamad MHCM; Massaro, Joseph PhD; Mahalingam, Meera MD, PhD, FRCPath

The American Journal of Dermatopathology: October 2012 - Volume 34 - Issue 7 - p 723–728
doi: 10.1097/DAD.0b013e31824b1ddf
Original Study

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.

*Pathology Department and Laboratory Medicine

Dermatopathology Section, Department of Dermatology

Department of Biostatistics, Boston University School of Medicine, Boston, MA.

The authors declare no conflicts of interest.

Reprints: Meera Mahalingam, MD, PhD, FRCPath, Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, 609 Albany St, J-301, Boston, MA 02118 (e-mail:

© 2012 Lippincott Williams & Wilkins, Inc.