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Bone Marrow Research
Volume 2012 (2012), Article ID 259351, 9 pages
Research Article

Differential Expression of Matrix Metalloproteinase-2 Expression in Disseminated Tumor Cells and Micrometastasis in Bone Marrow of Patients with Nonmetastatic and Metastatic Prostate Cancer: Theoretical Considerations and Clinical Implications—An Immunocytochemical Study

1Hematology, Division of Medicine, Hospital de Carabineros de Chile, Simón Bolívar 2200, Ñuñoa, 7770199 Santiago, Chile
2Instituto de Bio-Oncología, Avenida Salvador 95, Oficina 95, Providencia, 7500710 Santiago, Chile
3Circulating Tumor Cell Unit, Faculty of Medicine, Universidad Mayor, Renato Sánchez 4369, Las Condes, 7550224 Santiago, Chile
4Faculty of Medicine, Universidad Diego Portales, Manuel Rodriguez Sur 415, 8370179 Santiago, Chile
5Faculty of Medicine, Universidad Pontificia Católica de Chile, Avenida Libertador Bernardo O'Higgins 340, 8331150 Santiago, Chile
6Radiotherapy, Fundación Arturo López Pérez, Rancagua 899, Providencia, 7500921 Santiago, Chile

Received 21 May 2012; Accepted 18 October 2012

Academic Editor: Joseph H. Antin

Copyright © 2012 Nigel P. Murray et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Matrix metalloproteinase-2 (MMP-2) is important in the dissemination and invasion of tumor cells and activates angiogenesis. We present an immunocytochemical study of MMP-2 expression in circulating prostate cells (CPCs), disseminated tumor cells (DTCs), and micrometastasis (mM) in bone marrow of men with prostate cancer. Methods and Patients. Tumor cells were identified with anti-PSA immunocytochemistry. Positive samples underwent processing with anti-MMP-2, its expression was compared with Gleason score, concordance of expression, and metastatic and nonmetastatic disease. Results. 215 men participated, CPCs were detected in 62.7%, DTCs in 62.2%, and mM in 71.4% in nonmetastatic cancer; in metastatic cancer all had CPCs, DTCs, and mM detected. All CPCs and DTCs expressed MMP-2; in mM MMP-2 expression was positively associated with increasing Gleason score. MMP-2 expression in CPCs and DTCs showed concordance. In low grade tumors, mM and surrounding stromal cells were MMP-2 negative, with variable expression in high grade tumors; in metastatic disease, both mM and stromal cells were MMP-2 positive. Conclusions. CPCs and DTCs are different from mM, with inhibition of MMP-2 expression in mM of low grade tumors. With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors.