May Matthias, Siegsmund Michael, Hammermann Fränze, Loy Volker, Gunia Sven
Departments of Urology, Carl-Thiem Hospital Cottbus, Cottbus, Germany.
Scand J Urol Nephrol. 2007;41(5):375-81. doi: 10.1080/00365590701224445. Epub 2007 Jul 27.
Neuroendocrine (NE) cells in prostate cancer may influence tumor cell proliferation in a paracrine fashion. The aims of this study were to clarify the prognostic value of tumor cell proliferation and NE tumor cell differentiation in prostate cancer after radical prostatectomy, and to compare these parameters with each other.
Specimens were pooled from a total of 528 patients treated with radical prostatectomy without neoadjuvant hormonal therapy between 1996 and 2003. NE differentiation (NED) was determined by immunohistochemistry using antibodies directed against chromogranin A (CgA), and was scored as either NE-negative (0-1+) or -positive (2-3+). Tumor cell proliferation was assessed by means of the Ki-67 labeling index (Ki-67 LI). The mean post-surgical follow-up period was 49 months (range 10-116 months). Any subsequent rise in prostate-specific antigen (PSA) level was regarded as reflecting disease progression. The prognostic values of Ki-67 and CgA were comparatively analyzed using multivariate Cox regression.
NED was present in 6.1% of tumors. The mean Ki-67 LI was significantly higher in the CgA-positive group in comparison with CgA-negative specimens (6.6% vs 5.0%; p=0.029). The Ki-67 LI showed the highest correlations with Gleason score and pathological tumor stage (r=0.31 and r=0.3, respectively). NED was found to have the strongest association with pathological tumor stage (r=0.2). Multivariate analysis determined Gleason score > or =7 (4+3) [hazard ratio (HR) 3.04], NED (HR 1.89), lymph node metastases (HR 1.84), preoperative PSA level>20 ng/ml (HR 1.66), and Ki-67 LI > or = 5% (HR 1.62) to be significant predictors of biochemical progression.
Our results identify Ki-67 LI and NED as additional prognostic markers after radical prostatectomy.
前列腺癌中的神经内分泌（NE）细胞可能以旁分泌方式影响肿瘤细胞增殖。本研究的目的是阐明根治性前列腺切除术后肿瘤细胞增殖和NE肿瘤细胞分化在前列腺癌中的预后价值，并对这些参数进行相互比较。
收集了1996年至2003年间共528例行根治性前列腺切除术且未接受新辅助激素治疗患者的标本。使用抗嗜铬粒蛋白A（CgA）抗体通过免疫组织化学测定NE分化（NED），并将其分为NE阴性（0 - 1+）或阳性（2 - 3+）。通过Ki-67标记指数（Ki-67 LI）评估肿瘤细胞增殖。术后平均随访期为49个月（范围10 - 116个月）。前列腺特异性抗原（PSA）水平随后的任何升高都被视为反映疾病进展。使用多变量Cox回归对Ki-67和CgA的预后价值进行比较分析。
6.1%的肿瘤存在NED。与CgA阴性标本相比，CgA阳性组的平均Ki-67 LI显著更高（6.6%对5.0%；p = 0.029）。Ki-67 LI与Gleason评分和病理肿瘤分期的相关性最高（分别为r = 0.31和r = 0.3）。发现NED与病理肿瘤分期的关联最强（r = 0.2）。多变量分析确定Gleason评分≥7（4 + 3）[风险比（HR）3.04]、NED（HR 1.89）、淋巴结转移（HR 1.84）、术前PSA水平>20 ng/ml（HR 1.66）以及Ki-67 LI≥5%（HR 1.62）是生化进展的重要预测指标。
我们的结果确定Ki-67 LI和NED为根治性前列腺切除术后的额外预后标志物。
