MATRIX METALLOPROTEINASES 9 AND 14: TUMOR MICROENVIRONMENT MODULATORS IN TUMOR GROWTH AND INVASION, FOCUS ON BASAL CELL CARCINOMA AND SQUAMOUS CELL CARCINOMA OF HEAD AND NECK

Abstract

Background In tumor development, tumor, stromal, and inflammatory cells all release different matrix metalloproteinases (MMPs). MMPs rupture physical barriers, increase tumor induced angiogenesis, and disrupt local tissue to promote invasion and metastasis leading to poor prognosis. Objective MMP 9 and 14 expression in squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), respectively, to determine if any relation between MMPs expression with SCC grade and BCC subtype. Methods Forty-nine SCC and 42 BCC cases recruited, immunohistochemical staining of SCC and BCC with anti-MMP9 and 14 antibodies, respectively. Sections were microscopically scored: intensity (0-3), proportion (0-3), overall score (intensity + proportion). Tumors were categorized into low and high expression groups. Results SCC cases, 36.7% showed strong staining intensity of MMP9 antibody in tumor cells, 28.6% moderate, 32.7% weak, and only 2% were negative, while 51% cases had strong staining intensity in stroma adjacent to tumor, 26.5% moderate, 20.4% weak, and 2% were negative. For 6.1% cases overall, expression was weak, 93.9% showed high expression. Statistical relation between histologic grade and overall expression was significant. BCC cases, 47.6% showed strong staining intensity of MMP14 in tumor cells, 45.2% moderate and 7.1% had weak, while 35.7% cases had strong staining intensity in stroma, 45.2% moderate, and 19% cases showed weak. Statistical relation between overall expression for tumor and morphological grades of BCC was significant. Conclusions Results demonstrated marked expression of MMP 9 and 14 in high grade SCC and in high-risk morphological types of BCC, respectively. Hence, targeted therapy can help in preventing the tumor growth, invasion, and metastasis. In tumor development, tumor, stromal, and inflammatory cells all release different matrix metalloproteinases (MMPs). MMPs rupture physical barriers, increase tumor induced angiogenesis, and disrupt local tissue to promote invasion and metastasis leading to poor prognosis. MMP 9 and 14 expression in squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), respectively, to determine if any relation between MMPs expression with SCC grade and BCC subtype. Forty-nine SCC and 42 BCC cases recruited, immunohistochemical staining of SCC and BCC with anti-MMP9 and 14 antibodies, respectively. Sections were microscopically scored: intensity (0-3), proportion (0-3), overall score (intensity + proportion). Tumors were categorized into low and high expression groups. SCC cases, 36.7% showed strong staining intensity of MMP9 antibody in tumor cells, 28.6% moderate, 32.7% weak, and only 2% were negative, while 51% cases had strong staining intensity in stroma adjacent to tumor, 26.5% moderate, 20.4% weak, and 2% were negative. For 6.1% cases overall, expression was weak, 93.9% showed high expression. Statistical relation between histologic grade and overall expression was significant. BCC cases, 47.6% showed strong staining intensity of MMP14 in tumor cells, 45.2% moderate and 7.1% had weak, while 35.7% cases had strong staining intensity in stroma, 45.2% moderate, and 19% cases showed weak. Statistical relation between overall expression for tumor and morphological grades of BCC was significant. Results demonstrated marked expression of MMP 9 and 14 in high grade SCC and in high-risk morphological types of BCC, respectively. Hence, targeted therapy can help in preventing the tumor growth, invasion, and metastasis.