Tsihlias J, Kapusta L R, DeBoer G, Morava-Protzner I, Zbieranowski I, Bhattacharya N, Catzavelos G C, Klotz L H, Slingerland J M
Cancer Biology Research, Sunnybrook Health Science Center, Toronto, Ontario, Canada.
Cancer Res. 1998 Feb 1;58(3):542-8.
p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 in localized human prostate cancer. Archival material from 113 radical prostatectomy specimens obtained between 1985 and 1993 was stained immunohistochemically for p27Kip1 protein using a commercially available antibody. Patient charts were reviewed for preoperative serum prostate-specific antigen, clinical and pathological staging, Gleason tumor grade, time to biochemical and clinical recurrence, and survival. Strong p27Kip1 staining was uniformly seen in benign prostatic epithelial components in all tumor sections. p27Kip1 staining was reduced in most prostate cancers and was variable in prostatic intraepithelial neoplasia. Decreased p27Kip1 staining (<25% of nuclei stained positive for p27Kip1) correlated with seminal vesicle involvement (P = 0.0032) and with higher Gleason grade (P = 0.0114). On univariate analysis, low p27Kip1 predicted an increased risk of treatment failure in the node-negative cohort (P = 0.0037) and in the subset who did not receive neoadjuvant hormonal therapy (P = 0.049). Low p27Kip1 expression was an independent predictor of treatment failure on multivariate analysis of lymph node negative prostate cancers following radical retropubic prostatectomy (n = 102; P = 0.047). Seminal vesicle involvement (P = 0.034) and positive surgical margins (P = 0.047) were also independent prognostic factors for disease recurrence. In patients who received preoperative neoadjuvant hormonal therapy, low p27Kip1 in the pathological specimen was an even stronger predictor of outcome than it was in the entire group (n = 23, P = 0.015).
p27Kip1是一种细胞周期蛋白依赖性激酶抑制剂，通过介导细胞周期停滞在G1期来负向调节细胞增殖。本研究旨在评估p27Kip1在局限性人类前列腺癌中的预后价值。使用市售抗体对1985年至1993年间获得的113份根治性前列腺切除术标本的存档材料进行p27Kip1蛋白的免疫组织化学染色。查阅患者病历以了解术前血清前列腺特异性抗原、临床和病理分期、Gleason肿瘤分级、生化和临床复发时间以及生存率。在所有肿瘤切片的良性前列腺上皮成分中均一致可见强p27Kip1染色。大多数前列腺癌中p27Kip1染色减少，前列腺上皮内瘤变中p27Kip1染色存在差异。p27Kip1染色降低（<25%的细胞核p27Kip1染色呈阳性）与精囊受累相关（P = 0.0032）以及与更高的Gleason分级相关（P = 0.0114）。单因素分析显示，低p27Kip1预测淋巴结阴性队列（P = 0.0037）和未接受新辅助激素治疗的亚组（P = 0.049）治疗失败风险增加。在耻骨后根治性前列腺切除术后淋巴结阴性前列腺癌的多因素分析中（n = 102；P = 0.047），低p27Kip1表达是治疗失败的独立预测因素。精囊受累（P = 0.034）和手术切缘阳性（P = 0.047）也是疾病复发的独立预后因素。在接受术前新辅助激素治疗的患者中，病理标本中低p27Kip1比在整个组中更是结局的更强预测因素（n = 23，P = 0.015）。
