title: 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.
abstract: 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.
authors.affiliation: Hematology, Division of Medicine, Hospital de Carabineros de Chile, Simón Bolívar 2200, Ñuñoa, 7770199 Santiago, Chile ; Instituto de Bio-Oncología, Avenida Salvador 95, Oficina 95, Providencia, 7500710 Santiago, Chile ; Circulating Tumor Cell Unit, Faculty of Medicine, Universidad Mayor, Renato Sánchez 4369, Las Condes, 7550224 Santiago, Chile.
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Murray
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reyes
authors.forename: Pablo
authors.initials: P
authors.lastname: Tapia
authors.forename: Leonardo
authors.initials: L
authors.lastname: Badínez
authors.forename: Nelson
authors.initials: N
authors.lastname: Orellana