Todenhöfer Tilman, Hennenlotter Jörg, Faber Frank, Wallwiener Diethelm, Schilling David, Kühs Ursula, Aufderklamm Stefan, Bier Simone, Mischinger Johannes, Gakis Georgios, Fehm Tanja, Stenzl Arnulf, Schwentner Christian
Department of Urology, University Hospital, Tübingen, Germany; Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
Prostate. 2015 May;75(6):637-45. doi: 10.1002/pros.22947. Epub 2015 Jan 13.
Disseminated tumor cells (DTC) can be detected in a high proportion of patients with localized solid malignancies. In prostate cancer (PC), determination of DTCs is critically discussed as there are conflicting results on their prognostic value. The aim of the present study was to evaluate the presence and prognostic role of DTCs in PC patients with a high risk of disease recurrence.
248 patients with clinically localized PC undergoing radical prostatectomy with features of increased risk of recurrence (PSA ≥10 ng/ml or Gleason score ≥ 4 + 3 = 7 or pT ≥3) were included. All patients underwent intraoperative bone marrow (BM) aspiration biopsy. BM cells were evaluated by immunocytochemistry for cytokeratines and the apoptosis marker caspase-cleaved cytokeratin 18 (M30). Results of immunocytochemistry were correlated with clinical and pathological parameters and clinical outcome of the patients.
Of 248 patients, 47 (19.0%) had evidence of DTCs at time of radical prostatectomy. In 17 of these 47 patients (36.2%), DTCs expressed the apoptosis marker M30. We observed no correlation between the presence of DTCs and tumor stage, nodal stage, prostate-specific antigen, or Gleason score. After a median-follow-up of 58 months (23-76), no differences in rates of biochemical recurrence, development of metastases and cancer-specific death were observed between patients with and without DTCs while apoptosis markers had no role.
In a single-centre cohort of patients with increased risk for disease recurrence, the presence of DTCs at the time of prostatectomy does not influence clinical outcome. For the first time in patients with PC, DTCs were evaluated for immunocytological features indicating apoptosis. Due to conflicting results of studies on DTCs, BM biopsies at time of radical prostatectomy cannot be recommended as a standard procedure in patients with clinically localized PC.
在大部分局限性实体恶性肿瘤患者中均可检测到播散肿瘤细胞（DTC）。在前列腺癌（PC）中，DTCs的预后价值存在相互矛盾的结果，因此对其测定存在严格的讨论。本研究的目的是评估DTCs在疾病复发风险高的PC患者中的存在情况及其预后作用。
纳入248例临床局限性PC患者，这些患者接受了根治性前列腺切除术，具有复发风险增加的特征（PSA≥10 ng/ml或Gleason评分≥4+3=7或pT≥3）。所有患者均接受术中骨髓（BM）穿刺活检。通过免疫细胞化学评估BM细胞中的细胞角蛋白和凋亡标志物半胱天冬酶切割的细胞角蛋白18（M30）。免疫细胞化学结果与患者的临床和病理参数以及临床结局相关。
在248例患者中，47例（19.0%）在根治性前列腺切除术时存在DTCs证据。在这47例患者中的17例（36.2%）中，DTCs表达凋亡标志物M30。我们观察到DTCs的存在与肿瘤分期、淋巴结分期、前列腺特异性抗原或Gleason评分之间无相关性。中位随访58个月（23-76个月）后，有和没有DTCs的患者在生化复发率、转移发生情况和癌症特异性死亡方面未观察到差异，而凋亡标志物无作用。
在一个疾病复发风险增加的单中心队列患者中，前列腺切除术时DTCs的存在不影响临床结局。首次在PC患者中评估了DTCs的免疫细胞学特征以指示凋亡。由于关于DTCs的研究结果相互矛盾，不建议将根治性前列腺切除术时的BM活检作为临床局限性PC患者的标准程序。
