Ricciardelli C, Mayne K, Sykes P J, Raymond W A, McCaul K, Marshall V R, Tilley W D, Skinner J M, Horsfall D J
Departments of Surgery, Flinders University School of Medicine, Bedford Park, South Australia 5042.
Clin Cancer Res. 1997 Jun;3(6):983-92.
Curative therapies for clinically localized prostate cancer have significant morbidity, and those patients who might be cured by aggressive management are not easily identified using current clinical information. Better biomarkers of tumor behavior need to be identified to improve clinical outcome. Chondroitin sulfate (CS), a glycosaminoglycan, may be a potentially useful biomarker as it is known to influence cell growth and differentiation and might influence malignant progression. In this study, CS was immuno-localized to the periacinar and peritumoral fibromuscular stromal tissue of nonmalignant and malignant prostates. The CS concentration was increased in the prostate tissue of men with early-stage prostate cancer compared with tissue from men without cancer (P < 0.0001). Using Cox's univariate analysis, CS concentration, tumor grade, preoperative serum prostate-specific antigen (PSA), extracapsular extension of disease, positive surgical margins, and patient age were associated with an increased risk of PSA failure. The CS concentration was compared with the other features in two-variable regression analyses. CS and preoperative serum PSA concentrations were independent predictors of PSA failure. CS was a stronger prognostic feature than tumor grade and could predict outcome for patients with moderately differentiated tumors. Patients with a low CS concentration had significantly better progression-free survival following radical prostatectomy than patients with high levels of CS (Kaplan-Meier plot, 91% versus 49% PSA progression free at 5 years, respectively, P = 0.0038). Only postoperative pathological indices (extracapsular extension, surgical margins) were stronger predictors than CS. We conclude that measurement of prostatic CS concentrations at diagnosis may allow stratification of patients with early-stage prostate cancer for adjunctive or alternate therapies.
临床局限性前列腺癌的根治性治疗具有显著的发病率，而那些可能通过积极治疗治愈的患者，利用当前的临床信息很难识别出来。需要确定更好的肿瘤行为生物标志物，以改善临床结局。硫酸软骨素（CS）是一种糖胺聚糖，可能是一种潜在有用的生物标志物，因为已知它会影响细胞生长和分化，可能也会影响恶性进展。在本研究中，CS免疫定位在非恶性和恶性前列腺的腺泡周围及肿瘤周围的纤维肌肉基质组织中。与无癌男性的组织相比，早期前列腺癌男性的前列腺组织中CS浓度升高（P < 0.0001）。使用Cox单因素分析，CS浓度、肿瘤分级、术前血清前列腺特异性抗原（PSA）、疾病的包膜外扩展、手术切缘阳性以及患者年龄与PSA失败风险增加相关。在双变量回归分析中，将CS浓度与其他特征进行了比较。CS和术前血清PSA浓度是PSA失败的独立预测因素。CS是比肿瘤分级更强的预后特征，并且可以预测中度分化肿瘤患者的结局。CS浓度低的患者在根治性前列腺切除术后的无进展生存期明显优于CS水平高的患者（Kaplan-Meier曲线，5年时分别为91%和49%无PSA进展，P = 0.0038）。只有术后病理指标（包膜外扩展、手术切缘）是比CS更强的预测因素。我们得出结论，在诊断时测量前列腺CS浓度可能有助于对早期前列腺癌患者进行分层，以便采取辅助或替代治疗。
