Shariat Shahrokh F, Roudier Martine P, Wilcox George E, Kattan Michael W, Scardino Peter T, Vessella Robert L, Erdamar Sibel, Nguyen Cuong, Wheeler Thomas M, Slawin Kevin M
Baylor Prostate Center, Scott Department of Urology, Baylor College of Medicine, 6560 Fannin Street, Houston, TX 77030, USA.
Cancer Res. 2003 Aug 1;63(15):4662-70.
The objective is to compare the performance of immunohistochemistry (IHC) with that of reverse transcription (RT)-PCR for detecting clinically significant micrometastases in histopathologically normal archival pelvic lymph nodes (PLN) removed at radical prostatectomy from men with locally advanced nonmetastatic prostate cancer. We stained 1864 fixed, paraffin-embedded PLNs from 199 pT(3)N(0)M(0) prostate cancer patients for prostate-specific antigen (PSA) and cytokeratin. We also assessed human glandular kallikrein (hK2) expression in a subset of 164 patients. In addition, all PLN specimens were assayed for hK2 mRNA using a previously described RT-PCR assay. PSA and cytokeratin were expressed in the same 13 of 199 (7%) cases; hK2 was expressed in 3 of 164 (2%) cases. PSA/cytokeratin and hK2 expression were associated with cancer involvement of seminal vesicles, higher Gleason sum, and a positive RT-PCR-hK2 assay result. In standard postoperative multivariable models, IHC-PSA/IHC-Cytokeratin or IHC-hK2 was associated with prostate cancer progression, development of distant metastases, and prostate cancer-specific survival. However, when RT-PCR-hK2 assay result was added to the models, it was the sole predictor of clinical outcomes. Although IHC-PSA/IHC-Cytokeratin and IHC-hK2 were more specific for identifying patients who would suffer biochemical progression and develop metastases and who would ultimately die of prostate cancer, RT-PCR-hK2 was more sensitive and accurate. Although IHC for PSA, cytokeratin, and hK2 appear to be more specific methods for detecting biologically and clinically significant prostate cancer micrometastases in histopathologically normal PLN, RT-PCR-hK2 appears to be a more sensitive method that maintained a reasonable specificity. In pT(3)N(0) patients, a positive RT-PCR-hK2 assay result when performed on PLN was the strongest predictor of clinical outcomes after radical prostatectomy.
目的是比较免疫组织化学（IHC）与逆转录（RT）-PCR在检测局部晚期非转移性前列腺癌男性患者根治性前列腺切除术中切除的组织病理学正常存档盆腔淋巴结（PLN）中具有临床意义的微转移方面的性能。我们对199例pT(3)N(0)M(0)前列腺癌患者的1864个固定、石蜡包埋的PLN进行前列腺特异性抗原（PSA）和细胞角蛋白染色。我们还评估了164例患者亚组中的人腺体激肽释放酶（hK2）表达。此外，使用先前描述的RT-PCR检测法对所有PLN标本进行hK2 mRNA检测。PSA和细胞角蛋白在199例中的13例（7%）中同时表达；hK2在164例中的3例（2%）中表达。PSA/细胞角蛋白和hK2表达与精囊癌累及、较高的Gleason评分总和以及RT-PCR-hK2检测结果阳性相关。在标准术后多变量模型中，免疫组化PSA/免疫组化细胞角蛋白或免疫组化hK2与前列腺癌进展、远处转移的发生以及前列腺癌特异性生存相关。然而，当将RT-PCR-hK2检测结果加入模型时，它是临床结局的唯一预测指标。尽管免疫组化PSA/免疫组化细胞角蛋白和免疫组化hK2在识别将发生生化进展和转移以及最终死于前列腺癌的患者方面更具特异性，但RT-PCR-hK2更敏感和准确。尽管对PSA、细胞角蛋白和hK2进行免疫组化似乎是在组织病理学正常的PLN中检测具有生物学和临床意义的前列腺癌微转移的更特异方法，但RT-PCR-hK2似乎是一种更敏感的方法，同时保持了合理的特异性。在pT(3)N(0)患者中，对PLN进行RT-PCR-hK2检测结果阳性是根治性前列腺切除术后临床结局的最强预测指标。
