Waltregny D, Bellahcène A, Van Riet I, Fisher L W, Young M, Fernandez P, Dewé W, de Leval J, Castronovo V
Metastasis Research Laboratory, University of Liège, Belgium.
J Natl Cancer Inst. 1998 Jul 1;90(13):1000-8. doi: 10.1093/jnci/90.13.1000.
Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate whether BSP might also be expressed in human prostate cancer, which often metastasizes to bone, and be predictive for progression risk.
Tissue sections from 180 patients who had undergone a radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided.
Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses. After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%-47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% CI = 2.3%-20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P<.05) among patients with moderately differentiated tumors or with pathologically confined tumors.
To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas.
骨唾液蛋白（BSP）是一种骨基质蛋白，最近发现它在乳腺癌中异位表达，并且与该疾病的不良预后和骨转移的发生在统计学上具有显著相关性。这些数据促使我们研究BSP是否也在常转移至骨的人类前列腺癌中表达，并预测进展风险。
对180例因局限性前列腺癌接受根治性前列腺切除术患者的组织切片进行免疫组织化学分析，以检测BSP的表达。生化进展定义为血清前列腺特异性抗原水平升高0.5 ng/mL或更多。采用统计学分析评估病理结果与BSP表达水平之间的关联，并使用Cox比例风险模型确定哪些临床和组织学参数，包括分期、Gleason评分和BSP表达（免疫染色强度和范围），与生化进展独立相关。所有P值均为双侧。
在所检查的大多数前列腺癌病变（78.9%）中可检测到BSP表达，而相邻正常腺组织中无表达或低表达。在单变量和多变量分析中，均发现BSP表达与生化进展之间存在统计学显著关联。随访3年后，肿瘤高表达BSP的患者生化复发率为36.7%（95%置信区间[CI]=23.4%-47.7%），而肿瘤未表达或低表达该蛋白的患者生化复发率为12.1%（95% CI=2.3%-20.8%）（对数秩检验，P=0.0014）。BSP表达状态可在中度分化肿瘤或病理局限肿瘤患者中识别出具有更高生化进展风险的患者（对数秩检验，P<0.05）。
据我们所知，本研究首次证明BSP在人类前列腺癌中表达，并突出了该蛋白在临床局限的前列腺腺癌患者中的统计学显著预后价值。
