Miyake Hideaki, Kurahashi Toshifumi, Hara Isao, Takenaka Atsushi, Fujisawa Masato
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
BJU Int. 2007 Feb;99(2):315-20. doi: 10.1111/j.1464-410X.2006.06622.x. Epub 2006 Nov 28.
To clarify the significance of micrometastases in pelvic lymph nodes in patients treated by radical prostatectomy (RP) for prostate cancer after neoadjuvant hormonal therapy (NHT).
The study included 52 patients with clinically localized prostate cancer who received NHT followed by RP. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 989 lymph nodes isolated from the 52 patients were assessed by a fully quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We regarded specimens in which either PSA or PSMA mRNA were positive as showing the 'presence of micrometastasis'. Lymph node specimens were also stained immunohistochemically with an antibody against PSA.
Pathological examinations detected tumour cells in 11 lymph nodes from four patients, and real-time RT-PCR further identified micrometastasis in 40 lymph nodes from 19 patients with no pathological evidence of nodal involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 19 lymph nodes from 11 patients with pathologically negative nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including the pretreatment serum PSA level, biopsy Gleason score and surgical margin status. The biochemical recurrence-free survival rate in patients with no micrometastasis was significantly higher than that in those with micrometastasis. Furthermore, multivariate analysis identified the presence of micrometastasis as an independent factor predicting biochemical recurrence.
Although residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by routine pathological examination, the present results show the usefulness of quantitative real-time RT-PCR targeting PSA and PSMA genes for detecting micrometastatic tumour foci in pelvic lymph nodes from patients with localized prostate cancer treated by NHT followed by RP. Furthermore, the present findings suggest that micrometastases in pelvic lymph nodes might be, at least partly, important in the development of biochemical recurrence in some patients undergoing RP after NHT.
阐明新辅助激素治疗（NHT）后接受前列腺癌根治术（RP）的患者盆腔淋巴结微转移的意义。
本研究纳入52例临床局限性前列腺癌患者，这些患者先接受NHT，随后接受RP。通过全定量实时逆转录聚合酶链反应（RT-PCR）评估从这52例患者分离出的989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 mRNA呈阳性的标本视为显示“存在微转移”。淋巴结标本还用抗PSA抗体进行免疫组织化学染色。
病理检查在4例患者的11个淋巴结中检测到肿瘤细胞，实时RT-PCR进一步在19例无淋巴结受累病理证据的患者的40个淋巴结中鉴定出微转移。通过免疫组织化学染色在11例病理检查阴性的患者的19个淋巴结中证实了微转移癌细胞的存在。微转移的存在与其他传统预后变量显著相关，包括治疗前血清PSA水平、活检Gleason评分和手术切缘状态。无微转移患者的生化无复发生存率显著高于有微转移患者。此外，多变量分析确定微转移的存在是预测生化复发的独立因素。
尽管NHT后切除的淋巴结中萎缩性前列腺癌细胞的残留病灶通过常规病理检查难以诊断，但目前的结果表明，针对PSA和PSMA基因的定量实时RT-PCR对于检测接受NHT后再行RP的局限性前列腺癌患者盆腔淋巴结中的微转移肿瘤病灶是有用的。此外，目前的研究结果表明，盆腔淋巴结微转移在接受NHT后再行RP的一些患者的生化复发发展中可能至少部分起重要作用。
