De Cicco Concetta, Ravasi Laura, Zorzino Laura, Sandri Maria Teresa, Botteri Edoardo, Verweij Fabrizio, Granchi Donatella, de Cobelli Ottavio, Paganelli Giovanni
Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy.
Curr Cancer Drug Targets. 2008 May;8(3):199-206. doi: 10.2174/156800908784293613.
Prostate adenocarcinoma is generally characterized by slow progression although some phenotypes have a more aggressive behavior with tendency to local invasion and distant metastases, mainly to bones. Better specific care could be provided to the aggressive phenotype-group of patients if pre-surgical identification were available.
Correlations between pre-surgical levels of 6 blood molecules and pathological tumour staging, post-surgical Gleason score and disease-free survival have been observed. Plasma and sera from 162 men affected by prostate adenocarcinoma were analysed with ELISA to assess levels of neovascularization-related molecule (VEGF), endothelial cell adhesion molecule (VCAM), extracellular matrix destruction-related molecules (MMP-2, MMP-9), and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2).
The median values of serum determinations were for VEGF 279 pg/ml, VCAM 633 ng/ml, MMP-2 206 ng/ml and MMP-9 614 ng/ml. Plasma medians (ng/ml) were 94 for TIMP-1 and 90 for TIMP-2. Patients with VCAM values > 633 ng/ml had a worse disease-free survival than patients with values <633 ng/ml with an adjusted Hazard Ratio of 2.1, significant (95% confidence interval 0.8-5.6). Patients with levels of MMP-2 < 206 ng/ml showed an increased risk of progression (adjusted HR 1.7; 95% C.I. 0.6-4.8).
Levels of VCAM and MMP-2 should be checked in patients with prostate adenocarcinoma, because distant spread is more likely to occur in patients with high levels of VCAM and low levels of MMP-2. The scientific community should further investigate impact on prognosis of VCAM and MMP-2.
前列腺腺癌通常进展缓慢，尽管某些表型具有更具侵袭性的行为，有局部侵袭和远处转移的倾向，主要转移至骨骼。如果能够在术前进行识别，就能为侵袭性表型组的患者提供更好的针对性治疗。
观察了6种血液分子的术前水平与病理肿瘤分期、术后Gleason评分及无病生存期之间的相关性。采用酶联免疫吸附测定法（ELISA）分析了162例前列腺腺癌患者的血浆和血清，以评估与新生血管形成相关分子（血管内皮生长因子，VEGF）、内皮细胞黏附分子（血管细胞黏附分子，VCAM）、细胞外基质破坏相关分子（基质金属蛋白酶-2，MMP-2；基质金属蛋白酶-9，MMP-9）以及金属蛋白酶组织抑制剂（TIMP-1和TIMP-2）的水平。
血清检测的中位数分别为：VEGF 279 pg/ml、VCAM 633 ng/ml、MMP-2 206 ng/ml和MMP-9 614 ng/ml。血浆中位数（ng/ml）：TIMP-1为94，TIMP-2为90。VCAM值>633 ng/ml的患者无病生存期比VCAM值<633 ng/ml的患者更差，校正风险比为2.1，具有显著性（95%置信区间0.8 - 5.6）。MMP-2水平<206 ng/ml的患者疾病进展风险增加（校正风险比1.7；95%置信区间0.6 - 4.8）。
前列腺腺癌患者应检测VCAM和MMP-2水平，因为VCAM水平高且MMP-2水平低的患者更易发生远处转移。科学界应进一步研究VCAM和MMP-2对预后的影响。
