Miyake Hideaki, Hara Isao, Kurahashi Toshifumi, Inoue Taka-aki, Eto Hiroshi, Fujisawa Masato
Department of Urology, Kobe University School of Medicine, Kobe, Japan.
Clin Cancer Res. 2007 Feb 15;13(4):1192-7. doi: 10.1158/1078-0432.CCR-05-2706.
Routine pathologic examination can miss micrometastatic tumor foci in the lymph nodes of patients with prostate cancer, resulting in confusion during tumor staging and clinical decision-making. The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical prostatectomy for prostate cancer.
The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2,215 lymph nodes isolated from 120 patients with clinically localized prostate cancer was assessed by a fully quantitative real-time reverse transcriptase-PCR. We regarded specimens in which either PSA or PSMA mRNAs were positive as proof of the "presence of micrometastasis." Immunohistochemical staining of lymph node specimens with an antibody against PSA was also done.
Pathologic examinations detected tumor cells in 29 lymph nodes from 11 patients, and real-time reverse transcriptase-PCR further identified micrometastasis in 143 lymph nodes from 32 patients with no pathologic evidence of lymph node involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 61 lymph nodes from 17 patients with pathologically negative lymph nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including serum PSA value, pathologic stage, Gleason score, and tumor volume. Biochemical recurrence was detected in 32 patients, 17 of whom were negative for lymph node metastasis by pathologic examination (including 4 patients with pathologically organ-confined disease), but were diagnosed as having micrometastasis. Biochemical recurrence-free survival rate in patients without micrometastasis was significantly higher than in those with micrometastasis irrespective of the presence of pathologically positive nodes. Furthermore, only the presence of micrometastasis was independently associated with biochemical recurrence regardless of other factors examined.
These findings suggest that approximately 30% of clinically localized prostate cancers shed cancer cells to the pelvic lymph nodes, and that biochemical recurrence after radical prostatectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.
常规病理检查可能会遗漏前列腺癌患者淋巴结中的微转移瘤灶，从而在肿瘤分期和临床决策过程中造成混淆。本研究的目的是阐明在接受前列腺癌根治术的患者中，盆腔淋巴结微转移的意义。
通过全定量实时逆转录聚合酶链反应评估从120例临床局限性前列腺癌患者分离出的2215个淋巴结中前列腺特异性抗原（PSA）和前列腺特异性膜抗原（PSMA）的表达。我们将PSA或PSMA mRNAs呈阳性的标本视为“存在微转移”的证据。还用抗PSA抗体对淋巴结标本进行了免疫组织化学染色。
病理检查在11例患者的29个淋巴结中检测到肿瘤细胞，实时逆转录聚合酶链反应进一步在32例无淋巴结受累病理证据的患者的143个淋巴结中鉴定出微转移。免疫组织化学染色在17例病理阴性淋巴结患者的61个淋巴结中证实存在微转移癌细胞。微转移的存在与其他传统预后变量显著相关，包括血清PSA值、病理分期、Gleason评分和肿瘤体积。32例患者检测到生化复发，其中17例经病理检查淋巴结转移阴性（包括4例病理局限于器官的疾病患者），但被诊断为有微转移。无论病理阳性淋巴结是否存在，无微转移患者的生化无复发生存率均显著高于有微转移患者。此外，无论检查的其他因素如何，仅微转移的存在与生化复发独立相关。
这些发现表明，约30%的临床局限性前列腺癌会向盆腔淋巴结播散癌细胞，前列腺癌根治术后的生化复发至少部分可由盆腔淋巴结微转移解释。
