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Matrix Metalloproteinase Expression in Adenocarcinoma and Squamous Cell Carcinoma of the Lung
Sonam A. Shah1, John S. Ikonomidis2, Robert E. Stroud2, Eileen I. Chang2, Francis G. Spinale2, Carolyn E. Reed2; 1Medical University of South Carolina, College of Medicine, Charleston, SC; 2Medical University of South Carolina, Department of Surgery, Charleston, SC

Objective: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths. Matrix metalloproteinases (MMPs) are an endogenous proteinase system shown to facilitate cancer invasion and metastasis. The purpose of this study was to evaluate MMP expression in the two most common histologies of NSCLC, squamous cell (SCC) and adenocarcinoma (AC), relative to normal lung tissue.
Methods: A comprehensive MMP multiplex plate analysis was run on homogenates of 23 SCC and 22 AC surgically resected tumor specimens and compared (pg of MMP/mg tissue) to MMP concentrations in adjacent normal tissue. A subset analysis of patients who recurred versus those who did not was performed.
Results: Analysis of the combined tumor groups showed increased MMP abundance compared to normal tissue, with the exception of MMP-9 (MMP-1: tumor: 19.4*±5.1, normal: 0.4±0.1; MMP-2: tumor: 103.8*±18.3, normal: 39.2±5.0; MMP-3: tumor: 7.7*±2.4, normal: 0.4±0.1; MMP-8: tumor: 189.5*±41.3, normal: 61.0±8.9; MMP-9: tumor: 150.2±16.6, normal: 163.7±18.4; MMP-12: tumor: 16.1*±3.4, normal: 0.2±0.1; MMP-13: tumor: 2.6*±1.0, normal: 0.0±0.0; * p<0.05) ). Analysis of SCC tumor groups versus AC tumor groups revealed a distinct MMP profile for each histological subtype (data not shown). The profiles of histologic subtypes were then compared to each other (see figure). The subset analysis showed that only MMP-9 was significantly elevated in patients whose tumor recurred (MMP-1: recurred: 14.1±7.5, not: 14.4±3.5; MMP-2: recurred: 86.8±25.7, not: 76.2±11.4; MMP-3: 18.1±13.6, not: 4.4±1.4; MMP-8: recurred: 233.0±78.3, not: 109.3±27.2; MMP-9: recurred: 223.3*±31.7, not: 118.9±19.4; MMP-12: recurred: 27.7±11.9, not: 14.7±4.0; MMP-13: recurred: 10.1±7.3, not: 1.0±0.3; *p<0.05). All MMP values are listed in picograms of MMP per milligrams of tissue.
Conclusion: The results of this unique study demonstrated that MMP abundance and profiles for NSCLC are increased in tumor tissue over normal, and that there are disparate MMP concentration profiles for SCC versus AC. The subset analysis underscores that MMP-9 may be useful as a marker for recurrence. Continued understanding of the biochemical basis for lung cancer invasion and metastasis could be helpful in developing histology-specific screening tools, imaging modalities, and adjuvant therapy protocols for patients with stage I and II non-small cell lung cancer.


MMP Levels: Squamous Cell Carcinoma vs. Adenocarcinoma. MMP-1: SCC: 30.8*±9.3, AC: 6.8±2.1; MMP-2: SCC: 128.2*±30.1, AC: 52.1±8.1; MMP-3: SCC: 13.9*±4.3, AC: 0.9±0.2; MMP-8: SCC: 396.0*±93.5, AC: 31.2±8.6; MMP-9: SCC: 209.9*±19.5, AC: 65.1±16.2; MMP-12: SCC: 24.7*±5.7, AC: 4.9±1.2; MMP-13: SCC: 3.4*±1.9, AC: 1.4±0.4, *p<0.05. All values in pg of MMP/mg tissue.
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