Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate

• Published in: Clinical cancer research Vol. 3; no. 2; pp. 249 - 256
• Main Authors: MELCHIOR, S. W, COREY, E, ELLIS, W. J, ROSS, A. A, LAYTON, T. J, OSWIN, M. M, LANGE, P. H, VESSELLA, R. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-1997
• Subjects: Adult; Aged; Biological and medical sciences; Biopsy; Bone Marrow - pathology; Cell Count; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Nephrology. Urinary tract diseases; Prostate-Specific Antigen - analysis; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Sensitivity and Specificity; Tumors of the urinary system; Urinary tract. Prostate gland; Adenocarcinoma; Human; Urinary system disease; Prostate disease; Immunocytochemistry; Reverse transcription; Early stage; Malignant tumor; In vitro; Prostate specific antigen; Polymerase chain reaction; Established cell line; Advanced stage; Detection; Male genital diseases; Prostate; Tumor cell
• ISSN: 1078-0432; 1557-3265

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.