De Pinieux G, Flam T, Zerbib M, Taupin P, Bellahcène A, Waltregny D, Vieillefond A, Poupon M F
Laboratoire de Cytogénétique moléculaire et Oncologie, CNRS-Institut Curie, Departement de Biostatistiques, Institut Curie, CHU Cochin, Université Paris V, Paris Cedex, France.
J Urol. 2001 Nov;166(5):1924-30. doi: 10.1097/00005392-200111000-00085.
Skeletal metastases are the hallmark of advanced prostate cancer and recurrence after local surgery is common. Currently to our knowledge no biological markers predict the risk of disease progression in individuals with localized prostate cancer. In a search for predictive markers we evaluated the expression of bone sialoprotein and bone morphogenetic protein 6, 2 bone related proteins, and the angiogenic factor thymidine phosphorylase.
The study population included 43 men who presented with localized prostate cancer treated with radical prostatectomy. Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression was assessed by immunohistochemical testing. Results were analyzed in relation to pathological disease stage, Gleason score and clinical outcome. Clinical followup was 4.3 to 11.4 years after surgery (median 7.9).
Disease did not progress in 17 of the 43 cases, while recurrence and/or metastasis developed in the other 26 at a median of 6.5 and 6.9 years, respectively. Bone sialoprotein and bone morphogenetic protein 6 expression detected in 28 (65%) and 29 (67%) of the 43 samples, respectively, was significantly associated (p = 0.0001). Thymidine phosphorylase detected in 26 samples (60%) was not related to bone sialoprotein and/or bone morphogenetic protein 6 positivity. Bone sialoprotein and/or bone morphogenetic protein 6 expression correlated with bone metastasis, while thymidine phosphorylase expression was related to local recurrence (p = 0.002 and/or 0.007, and 0.00007, respectively). On multivariate analysis only the correlation of thymidine phosphorylase expression with recurrence remained statistically significant (p = 0.002). Co-expression of the 3 markers was observed in the samples of 10 of the 11 patients (90%) with bone metastases and only in 5 of the 17 (29%) who were disease-free.
This study indicates that the expression of bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase determined at a clinically early stage of disease by a simple immunohistochemical technique would enable subgroups of patients to be identified that are at different risks of bone metastasis or recurrence. Detection of such markers would provide additional prognostic information that would be useful for patients with intermediate or low Gleason score or stage disease. These patients would benefit from a more adapted clinical follow-up.
骨转移是晚期前列腺癌的标志，局部手术后复发很常见。据我们所知，目前尚无生物学标志物可预测局限性前列腺癌患者疾病进展的风险。为了寻找预测性标志物，我们评估了骨唾液蛋白、骨形态发生蛋白6这两种与骨相关的蛋白以及血管生成因子胸苷磷酸化酶的表达。
研究人群包括43例接受根治性前列腺切除术治疗的局限性前列腺癌男性患者。通过免疫组织化学检测评估骨唾液蛋白、骨形态发生蛋白6和胸苷磷酸化酶的表达。根据病理疾病分期、Gleason评分和临床结果对结果进行分析。术后临床随访时间为4.3至11.4年（中位时间7.9年）。
43例患者中17例疾病未进展，而另外26例分别在中位时间6.5年和6.9年出现复发和/或转移。在43个样本中，分别有28个（65%）和29个（67%）检测到骨唾液蛋白和骨形态发生蛋白6的表达，二者显著相关（p = 0.0001）。在26个样本（60%）中检测到的胸苷磷酸化酶与骨唾液蛋白和/或骨形态发生蛋白6的阳性无关。骨唾液蛋白和/或骨形态发生蛋白6的表达与骨转移相关，而胸苷磷酸化酶的表达与局部复发相关（分别为p = 0.002和/或0.007，以及0.00007）。多因素分析显示，仅胸苷磷酸化酶表达与复发的相关性仍具有统计学意义（p = 0.002）。在11例骨转移患者中的10例（90%）样本中观察到这3种标志物的共表达，而在17例无疾病患者中仅5例（29%）样本中观察到。
本研究表明，通过简单的免疫组织化学技术在疾病临床早期测定骨唾液蛋白、骨形态发生蛋白6和胸苷磷酸化酶的表达，能够识别出具有不同骨转移或复发风险的患者亚组。检测这些标志物将提供额外的预后信息，对Gleason评分或疾病分期为中等或低水平的患者有用。这些患者将受益于更具针对性的临床随访。
