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

الملخص EN

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.