Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
Clin Cancer Res. 2010 Dec 1;16(23):5908-13. doi: 10.1158/1078-0432.CCR-10-1200.
Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. Previous studies have suggested that Cyr61 may be a marker for a more aggressive phenotype. In this study, we evaluated the association between Cyr61 staining intensity and subsequent recurrence after surgical treatment of clinically localized prostate cancer.
A study of 229 men with recurrence and 229 controls matched on age, race, pathologic stage, and Gleason sum nested in a cohort of men who underwent radical prostatectomy for clinically localized prostate cancer, utilizing immunohistochemistry analysis of tissue microarray (TMA) sections, was conducted. Odds ratios (OR) of recurrence and 95% confidence intervals (CIs) were estimated using conditional logistic regression.
Recurrence was identified in 12.2% of cases, and in 24.0% of controls that had at least 1 TMA spot containing cancer with a staining intensity of 3 (P = 0.001). Taking into account age, pathologic stage and grade, presurgery prostate-specific antigen concentration, and calendar of surgery as a measure of tissue block storage time, men with a Cyr61 staining intensity of 3 were 56% less likely to recur than men with a lower staining intensity (OR = 0.44, 95% CI = 0.22-0.90).
High Cyr61 staining intensity in adenocarcinoma was associated with a lower risk of recurrence after surgical treatment of prostate cancer independent of pathologic tumor characteristics. If validated in other sample sets, Cyr61 may serve as a tissue biomarker for stratifying men for risk of recurrence and thus could inform treatment decision making.
富含半胱氨酸的血管生成诱导因子 61(Cyr61)是一种细胞外基质蛋白,参与生长因子和激素信号的转导。先前的研究表明,Cyr61 可能是更具侵袭性表型的标志物。在这项研究中,我们评估了 Cyr61 染色强度与临床局限性前列腺癌手术后复发之间的关系。
这项研究纳入了 229 例复发患者和 229 例年龄、种族、病理分期和 Gleason 评分相匹配的对照组,这些患者在接受临床局限性前列腺癌根治性前列腺切除术时,利用组织微阵列(TMA)切片的免疫组织化学分析进行了嵌套队列研究。使用条件逻辑回归估计复发的比值比(OR)和 95%置信区间(CI)。
在 12.2%的病例中发现了复发,在 24.0%的对照组中至少有一个 TMA 点含有染色强度为 3 的癌症(P = 0.001)。考虑到年龄、病理分期和分级、术前前列腺特异性抗原浓度以及手术时间作为组织块储存时间的衡量标准,染色强度为 3 的 Cyr61 男性复发的可能性比染色强度较低的男性低 56%(OR = 0.44,95%CI = 0.22-0.90)。
腺癌中高 Cyr61 染色强度与前列腺癌手术后复发风险降低独立相关,与病理肿瘤特征无关。如果在其他样本集中得到验证,Cyr61 可能成为分层男性复发风险的组织生物标志物,从而为治疗决策提供信息。