Murray Nigel P, Reyes Eduardo, Salazar Anibal, Lopez Marco Antonio, Orrego Shenda, Guzman Eghon
University Finis Terrae, Faculty of Medicine, Santiago, Chile.
Urology Service, Hospital DIPRECA; University Diego Portales, Faculty of Medicine, Santiago, Chile.
Turk J Urol. 2020 Mar 11;46(3):186-195. doi: 10.5152/tud.2020.19219. Print 2020 May.
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.
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.
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.
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.
原发性肿瘤中基质金属蛋白酶-2（MMP-2）的表达与预后较差相关，但目前对于微转移中的表达、与循环前列腺细胞（CPCs）的关联及预后了解甚少。
这是一项对接受根治性前列腺切除术的男性进行的前瞻性研究。术后1个月采集骨髓和血液样本。使用抗前列腺特异性抗原的免疫细胞化学鉴定微转移和CPCs，并用抗MMP-2测定MMP-2表达。记录病理分期、Gleason评分及生化复发时间；同时，确定10年的Kaplan-Meier无生化复发生存率和受限平均无生化复发生存时间。
共有282名男性参与，其中54名（19%）有微转移但无CPCs（B组），88名（31%）有微转移且有CPCs（C组）。C组男性中MMP-2表达的微转移频率更高，为63%，而B组为12%（p<0.001），骨髓微转移中的MMP-2表达与更高的Gleason评分相关（p<0.05），以及更高的治疗失败频率和更短的治疗失败时间。此外，记录到10年的Kaplan-Meier无生化复发生存率在MMP-2阳性与阴性时分别为0%和7.7%，平均生化复发时间分别为2.6年和4.0年。
骨髓微转移中MMP-2的表达与更高的Gleason评分、CPCs的存在、更高的失败频率和更短的失败时间相关，可能在临床上有助于识别治疗失败高危男性。
