Vis A N, Noordzij M A, Fitoz K, Wildhagen M F, Schröder F H, van der Kwast T H
Department of Pathology, Josephine Nefkens Institute, Erasmus University, Rotterdam, The Netherlands.
J Urol. 2000 Dec;164(6):2156-61.
Molecular tissue markers may give the clinician additional information about patients with prostate cancer at risk for treatment failure after retropubic radical prostatectomy. We substantiate the prognostic value of 3 tissue markers, the cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s, in addition to more conventional pathological prognosticators in an historical (before prostate specific antigen) cohort of patients with prostate cancer.
Representative tumor sections from 92 patients who underwent retropubic radical prostatectomy were immunohistochemically stained with antibodies against p27(kip1), MIB-1 (Ki-67) and CD44s, and assessed in a semiquantitative manner. Gleason score and pathological tumor stage were recorded. All variables were correlated with clinical progression and disease specific survival on univariate and multivariate analyses.
On univariate analysis low (less than 50%) p27(kip1), high (10% or greater) MIB-1 and loss of CD44s expression were significantly associated with clinical outcome parameters, although MIB-1 did not reach statistical significance for disease specific survival. All 3 molecules were highly correlated with Gleason score and pathological tumor stage. Multivariate analysis showed that low p27kip1 was independent of grade and stage in predicting clinical recurrence (p <0.001) and disease specific survival (p = 0.045), while loss of CD44s was an additional independent prognostic factor for clinical recurrence (p = 0.02).
Reduced p27(kip1) expression is an independent predictor of poor outcome in prostate cancer, while MIB-1 is not. Decreased expression of CD44s yields additional information in predicting clinical recurrence. These tissue markers may identify patients at risk for disease recurrence after retropubic radical prostatectomy who may benefit from adjuvant therapy.
分子组织标志物可为临床医生提供更多关于耻骨后根治性前列腺切除术后有治疗失败风险的前列腺癌患者的信息。我们证实了3种组织标志物,即细胞周期蛋白p27(kip1)和MIB-1以及细胞粘附蛋白CD44s,在一组前列腺癌历史队列(在前列腺特异性抗原出现之前)中的预后价值,此外还有更传统的病理预后指标。
对92例行耻骨后根治性前列腺切除术患者的代表性肿瘤切片进行免疫组织化学染色,用抗p27(kip1)、MIB-1(Ki-67)和CD44s抗体进行检测,并进行半定量评估。记录 Gleason 评分和病理肿瘤分期。在单变量和多变量分析中,将所有变量与临床进展和疾病特异性生存进行相关性分析。
在单变量分析中,低水平(低于50%)的p27(kip1)、高水平(10%或更高)的MIB-1和CD44s表达缺失与临床结局参数显著相关,尽管MIB-1在疾病特异性生存方面未达到统计学意义。所有这3种分子与Gleason评分和病理肿瘤分期高度相关。多变量分析显示,低水平的p27kip1在预测临床复发(p<0.001)和疾病特异性生存(p = 0.045)方面独立于分级和分期,而CD44s缺失是临床复发的另一个独立预后因素(p = 0.02)。
p27(kip1)表达降低是前列腺癌预后不良的独立预测因素,而MIB-1不是。CD44s表达降低在预测临床复发方面提供了额外信息。这些组织标志物可识别耻骨后根治性前列腺切除术后有疾病复发风险且可能从辅助治疗中获益的患者。