Melchior S W, Corey E, Ellis W J, Ross A A, Layton T J, Oswin M M, Lange P H, Vessella R L
Department of Urology, Johannes Gutenberg University, 55131 Mainz, Germany.
Clin Cancer Res. 1997 Feb;3(2):249-56.
Because a significant number of patients with pathologically organ-confined carcinoma of the prostate subsequently develop recurrent disease, metastasis may occur much earlier than previously believed. We have used a reverse transcription-PCR assay for prostate-specific antigen mRNA and an immunocytochemical staining method for cytokeratins to test this hypothesis in paired peripheral blood (PB) and bone marrow (BM) specimens from 71 patients with clinically localized disease before radical prostatectomy, 14 patients with advanced-stage carcinoma of the prostate, and 30 controls (young healthy volunteers, patients without prostate disease, and patients with benign prostatic hyperplasia). Controls were negative in BM and PB. Fifty-six% of patients with organ-confined tumors (pT2) and 73% of those with extracapsular extension (pT3) were positive in the BM versus 16% of those with pT2 tumors and 27% of those with pT3 tumors in the PB. Patients with advanced-stage disease were positive in 86% of BM versus 71% of PB. The sensitivity of the immunocytochemistry assay to detect tumor cells was lower as compared with the reverse transcription-PCR assay. The results suggest that tumor cell dissemination occurs early during disease progression. Prostate cells seem to preferentially concentrate in the BM rather than the PB, which may be due to sequestration there by homing mechanisms. As the rate of detection in the BM exceeds the proportion of patients with subsequently progressing disease, we hypothesize that only a subset of these cells can survive in the BM and evolve to clinically apparent disease.
由于大量病理诊断为器官局限性前列腺癌的患者随后会出现疾病复发，转移可能比之前认为的要早得多。我们使用了一种用于检测前列腺特异性抗原mRNA的逆转录聚合酶链反应（RT-PCR）检测方法以及一种用于细胞角蛋白的免疫细胞化学染色方法，在71例前列腺癌根治术前临床局限性疾病患者、14例晚期前列腺癌患者以及30例对照（年轻健康志愿者、无前列腺疾病患者和良性前列腺增生患者）的配对外周血（PB）和骨髓（BM）标本中验证这一假设。对照组的骨髓和外周血检测结果均为阴性。器官局限性肿瘤（pT2）患者中有56%、包膜外侵犯（pT3）患者中有73%的骨髓检测呈阳性，而外周血中pT2肿瘤患者为16%，pT3肿瘤患者为27%。晚期疾病患者骨髓检测阳性率为86%，外周血为71%。与逆转录聚合酶链反应检测相比，免疫细胞化学检测法检测肿瘤细胞的敏感性较低。结果表明，肿瘤细胞播散在疾病进展早期就已发生。前列腺细胞似乎更倾向于聚集在骨髓而非外周血中，这可能是由于归巢机制使其在骨髓中滞留。由于骨髓中的检测率超过了随后疾病进展患者的比例，我们推测这些细胞中只有一部分能够在骨髓中存活并发展为临床显性疾病。
