Nigel P Murray1, Eduardo Reyes2, Anibal Salazar3, Marco Antonio Lopez4, Shenda Orrego4, Eghon Guzman4. 1. University Finis Terrae, Faculty of Medicine, Santiago, Chile. 2. Urology Service, Hospital DIPRECA; University Diego Portales, Faculty of Medicine, Santiago, Chile. 3. Urology Service, Hospital DIPRECA, Santiago, Chile. 4. University Mayor, Faculty of Medicine, Santiago, Chile.
Abstract
OBJECTIVE: The expression of matrix-metalloproteinase-2 (MMP-2) in the primary tumor is associated with a worse prognosis but little is known at this time regarding the expression in micro-metastasis, the association with circulating prostate cells (CPCs), and outcome. MATERIAL AND METHODS: This was a prospective study of men undergoing radical prostatectomy. Bone marrow and blood samples were taken at one month after surgery. Micro-metastasis and CPCs were identified using immunocytochemistry with anti-prostate specific-antigen and MMP-2 expression determined with anti-MMP-2. Pathological stage, Gleason score, and time to biochemical failure were recorded; meanwhile, Kaplan-Meier biochemical failure-free survival and restricted mean biochemical failure-free survival times for 10 years were determined. RESULTS: A total of 282 men participated, 54 (19%) of whom had micro-metastasis but not CPCs (group B) and 88 (31%) of whom had micro-metastasis and CPCs (group C). Men in group C had a higher frequency of MMP-2 expressing micro-metastasis at 63% versus 12% (p<0.001), and MMP-2 expression in bone marrow micro-metastasis was associated with a higher Gleason score (p<0.05) as well as a higher frequency of and shorter time to treatment failure. Also, a 10-year Kaplan-Meier biochemical failure-free survival rate of 0% versus 7.7% (MMP-2 positive versus negative) and a mean time to biochemical failure of 2.6 versus 4.0 years were recorded. CONCLUSION: The expression of MMP-2 in bone marrow micro-metastasis is associated with a higher Gleason score, the presence of CPCs, and a higher frequency of and shorter time to failure and could be clinically useful for identifying men at high risk of treatment failure.
OBJECTIVE: The expression of matrix-metalloproteinase-2 (MMP-2) in the primary tumor is associated with a worse prognosis but little is known at this time regarding the expression in micro-metastasis, the association with circulating prostate cells (CPCs), and outcome. MATERIAL AND METHODS: This was a prospective study of men undergoing radical prostatectomy. Bone marrow and blood samples were taken at one month after surgery. Micro-metastasis and CPCs were identified using immunocytochemistry with anti-prostate specific-antigen and MMP-2 expression determined with anti-MMP-2. Pathological stage, Gleason score, and time to biochemical failure were recorded; meanwhile, Kaplan-Meier biochemical failure-free survival and restricted mean biochemical failure-free survival times for 10 years were determined. RESULTS: A total of 282 men participated, 54 (19%) of whom had micro-metastasis but not CPCs (group B) and 88 (31%) of whom had micro-metastasis and CPCs (group C). Men in group C had a higher frequency of MMP-2 expressing micro-metastasis at 63% versus 12% (p<0.001), and MMP-2 expression in bone marrow micro-metastasis was associated with a higher Gleason score (p<0.05) as well as a higher frequency of and shorter time to treatment failure. Also, a 10-year Kaplan-Meier biochemical failure-free survival rate of 0% versus 7.7% (MMP-2 positive versus negative) and a mean time to biochemical failure of 2.6 versus 4.0 years were recorded. CONCLUSION: The expression of MMP-2 in bone marrow micro-metastasis is associated with a higher Gleason score, the presence of CPCs, and a higher frequency of and shorter time to failure and could be clinically useful for identifying men at high risk of treatment failure.
Authors: N P Murray; E Reyes; P Tapia; L Badinez; N Orellana; C Fuentealba; R Olivares; J Porcell; R Dueñas Journal: Int J Mol Med Date: 2012-07-20 Impact factor: 4.101
Authors: E Borgen; B Naume; J M Nesland; G Kvalheim; K Beiske; O Fodstad; I Diel; E F Solomayer; P Theocharous; R C Coombes; B M Smith; E Wunder; J P Marolleau; J Garcia; K Pantel Journal: Cytotherapy Date: 1999 Impact factor: 5.414
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