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DETECTION OF CIRCULATING PROSTATE SPECIFIC ANTIGEN EXPRESSING PROSTATIC CELLS IN THE BONE MARROW OF RADICAL PROSTATECTOMY PATIENTS BY SENSITIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION

1999; Lippincott Williams & Wilkins; Volume: 161; Issue: 4 Linguagem: Inglês

10.1016/s0022-5347(01)61592-1

1527-3792

CHUNG-LING GAO, Robert C. Dean, Angela Di Pinto, Renee Mooneyhan, Roger R. Connelly, David G. McLeod, Shiv Srivastava, Judd W. Moul,

Urologic and reproductive health conditions

No AccessJournal of UrologyClinical Urology: Original Articles1 Apr 1999DETECTION OF CIRCULATING PROSTATE SPECIFIC ANTIGEN EXPRESSING PROSTATIC CELLS IN THE BONE MARROW OF RADICAL PROSTATECTOMY PATIENTS BY SENSITIVE REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION CHUNG-LING GAO, ROBERT C. DEAN, ANGELA PINTO, RENEE MOONEYHAN, ROGER R. CONNELLY, DAVID G. McLEOD, SHIV SRIVASTAVA, and JUDD W. MOUL CHUNG-LING GAOCHUNG-LING GAO , ROBERT C. DEANROBERT C. DEAN , ANGELA PINTOANGELA PINTO , RENEE MOONEYHANRENEE MOONEYHAN , ROGER R. CONNELLYROGER R. CONNELLY , DAVID G. McLEODDAVID G. McLEOD , SHIV SRIVASTAVASHIV SRIVASTAVA , and JUDD W. MOULJUDD W. MOUL View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)61592-1AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The reverse transcriptase polymerase chain reaction (RT-PCR) assay for prostate specific antigen (PSA) expressing cells in the blood circulation has been under intense investigation since 1992. Although it has been suggested that this technology could be used as molecular staging for occult prostatic hematogenous metastases, we have been unable to confirm RT-PCR PSA positivity of peripheral blood to predict stage or recurrence in radical prostatectomy cases. We performed bone marrow RT-PCR PSA assay on a large cohort of radical prostatectomy cases and evaluate the use of this assay in improving prostate cancer staging and detecting early recurrence. Materials and Methods: Unilateral anterior iliac crest bone marrow aspirates were performed on 116 patients immediately before radical prostatectomy between February 1995 and September 1997. Radical prostatectomy specimens were processed as whole mounts. A sensitive nested RT-PCR assay with specific primers derived from the PSA sequence was used, which enabled us to detect PSA expressing LNCaP prostate cancer cells at the sensitivity of 1 cancer cell per 10 million lymphocytes (1/107). A minimum of 3 RT-PCR PSA reactions were performed on all patients and at least 2 positive tests were required to define positivity. Patients were followed for PSA recurrence (mean followup 14.7 months). Results: PSA expressing cells were detected in bone marrow of 51 of 116 patients (44.0%) when at least 2 of 3 RT-PCR PSA assays per patient were positive. A much higher rate of RT-PCR PSA positivity was noted (77/116 patients, 66.3%) when any RT-PCR PSA positivity was considered. In 10 randomly selected cases the RT-PCR product was confirmed as PSA by deoxyribonucleic acid sequencing. Of 51 bone marrow RT-PCR positive cases 25 (49%) had organ confined disease and 26 (51%) had nonorgan confined disease. Similarly, bone marrow RT-PCR PSA was not associated with age, race, grade, pretreatment PSA or prostatic acid phosphatase value, clinical stage or margin status. However, the 2-year disease-free survival was 96.6% in RT-PCR negative patients versus 77.5% in RT-PCR positive patients (p = 0.054), and bone marrow RT-PCR PSA was an independent prognostic factor in multivariate analysis including PSA, Gleason grade and pathological stage. Conclusions: Bone marrow RT-PCR PSA positivity in this study did not predict pathological stage, grade or margin positivity as determined from whole mount prostate cancer specimens. Furthermore, no relationship with age, grade or serum markers and bone marrow RT-PCR PSA positivity was noted. However, bone marrow RT-PCR PSA was associated with early disease recurrence. Further studies and longer followup are warranted to define the metastatic potential of the PSA expressing cells in the bone marrow of prostate cancer patients. References 1 : Diagnosis of chronic myeloid and acute lymphoblastic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc. Natl. Acad. Sci.1988; 85: 5698. Google Scholar 2 : The use of the polymerase chain reaction to detect metastatic prostate cancer cells in lymph nodes and bone marrow. Proc. Amer. Assn. Cancer Res.1992; 33: 396. Google Scholar 3 : Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res.1992; 53: 6110. Google Scholar 4 : Molecular staging of prostate cancer with the use of an enhanced reverse transcriptase-PCR assay. Urology1994; 45: 765. Google Scholar 5 : Enhanced reverse transcriptase-polymerase chain reaction for prostate specific antigen as an indicator of true pathologic stage in patients with prostate cancer. Cancer1995; 75: 1642. Google Scholar 6 : Molecular staging of genitourinary malignancies. Urology1996; 47: 948. Google Scholar 7 : Preoperative reverse transcriptase polymerase chain reaction for prostate specific antigen predicts treatment failure following radical prostatectomy. J. Urol.1996; 155: 1557. Link, Google Scholar 8 : Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications. J. Clin. Oncol.1995; 13: 1195. Google Scholar 9 : Prognostic significance of detection of prostate specific antigen transcripts in the peripheral blood of patients with metastatic androgen-independent prostatic carcinoma. Urology1997; 50: 100. Google Scholar 10 : Quantitative polymerase chain reaction does not improve preoperative prostate cancer staging: a clinico-pathological molecular analysis of 121 patients. J. Urol.1996; 156: 1560. Abstract, Google Scholar 11 : Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate. Clin. Cancer Res.1997; 3: 249. Google Scholar 12 : Prostate specific antigen reverse transcriptase-polymerase chain reaction assay in preoperative staging of prostate cancer. J. Urol.1997; 158: 1870. Link, Google Scholar 13 : Increased analytical sensitivity of RT-PCR of PSA mRNA decreases diagnostic specificity of detection of prostate cells in blood. Int. J. Cancer1996; 70: 52. Google Scholar 14 : The use of RT-nested-PCR of prostate specific antigen to detect hematogenous neoplastic cells in patients with prostate cancer. J. Mol. Med.1997; 75: 751. Google Scholar 15 : Value of the preoperative detection of prostate specific antigen positive circulating cells by nested RT-PCR in patients submitted to radical prostatectomy. Eur. Urol.1997; 32: 69. Google Scholar 16 : Positive prostate specific antigen circulating cells detected by reverse transcriptase polymerase chain reaction does not imply the presence of prostatic micrometastases. Urology1997; 50: 245. Google Scholar 17 : Evaluation of reverse transcriptase polymerase chain reaction (RT-PCR) prostate specific antigen assay for molecular staging of prostate cancer. Proc. Amer. Assn. Cancer Res.1997; 38: 1803. Google Scholar 18 : Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison to prostate-specific membrane antigen and prostate-specific antigen-based assays. Cancer Res.1994; 54: 6306. Google Scholar 19 : Detection of circulating prostate cells by reverse-transcriptase polymerase chain reaction of human glandular kallikrein (hK2) and prostate specific antigen (PSA) messages. Urology1997; 20: 184. Google Scholar 20 : Identification of bone marrow micrometastases in patients with prostate cancer. Cancer1994; 74: 2533. Google Scholar 21 : Presence of circulating prostate cells in bone marrow of patients undergoing radical prostatectomy is predictive of disease free survival. J. Clin. Oncol.1997; 15: 3451. Google Scholar 22 : Detection of micrometastatic prostate cancer cells in lymph nodes by reverse transcriptase polymerase chain reaction. Cancer Res.1993; 53: 5350. Google Scholar 23 : A rapid and simple method for the detection of prostate specific antigen mRNA in archival tissue specimens using a reverse transcription polymerase chain reaction assay. Urology1995; 45: 597. Google Scholar 24 : Prospective analysis of prostate specific markers in pelvic lymph nodes of patients with high-risk prostate cancer. J. Natl. Cancer Inst.1997; 89: 1498. Google Scholar 25 : Limitations of reverse transcriptase polymerase chain reaction analyses for detection of micrometastatic epithelial cancer cells in bone marrow. J. Clin. Oncol.1997; 15: 2701. Google Scholar 26 : Reverse transcriptase polymerase chain reaction for prostate specific antigen in the management of prostate cancer. J. Urol.1997; 158: 326. Link, Google Scholar 27 : Molecular forms of prostate specific antigen and the human kallikrein gene family: a new era. Urology1995; 45: 729. Google Scholar 28 : Cancer statistics. CA1997; 47: 5. Google Scholar 29 : The clinical usefulness of prostate-specific antigen: update 1998. J. Urol.1994; 152: 1358. Abstract, Google Scholar 30 : New prognostic factors in prostate carcinoma. Eur. Urol.1993; 24: 438. Google Scholar 31 : Grading of prostate carcinoma. Cancer Chemother. Rep.1975; 59: 111. Google Scholar 32 : An assessment of radical prostatectomy. Time trends, geographical variations and outcomes. J.A.M.A.1993; 269: 2633. Google Scholar 33 : Allelic loss in locally metastatic, multi-sampled prostate cancer. Cancer Res.1994; 54: 3273. Google Scholar 34 : A structured literature review of treatment for localized CaP. Arch. Fam. Med.1993; 2: 487. Google Scholar 35 : CaP: diagnosis, treatment, and experience at one tertiary medical center, 1989–1994. Mil. Med.1996; 161: 646. Google Scholar 36 : PSA RT-PCR in bone marrow aspirates following radical prostatectomy. J. Urol.1998; 159: 290. abstract 1119. Google Scholar 37 : cDNA coding for the entire human prostate specific antigen shows high homologies to the human tissue kallikrein genes. Biochem Biophys Res. Comm.1989; 160: 903. Google Scholar From the Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and Urology Service, Walter Reed Army Medical Center, Washington, D. C.Supported by United States Veterans Administration Grant 19963211035, and United States Army Research and Material Command program grant to the Henry M. Jackson Foundation for the Advancement of Military Medicine for the Center for Prostate Disease Research.The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the United States Army or the Department of Defense.(Moul) Requests for reprints: Department of Surgery, Uniformed Services University of the Health Sciences (USUHS), 4301 Jones Bridge Rd., Bethesda, Maryland 20814-4799.© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byPALMBERG C, KOIVISTO P, KAKKOLA L, TAMMELA T, KALLIONIEMI O and VISAKORPI T (2018) ANDROGEN RECEPTOR GENE AMPLIFICATION AT PRIMARY PROGRESSION PREDICTS RESPONSE TO COMBINED ANDROGEN BLOCKADE AS SECOND LINE THERAPY FOR ADVANCED PROSTATE CANCERJournal of Urology, VOL. 164, NO. 6, (1992-1995), Online publication date: 1-Dec-2000.Okegawa T, Nutahara K and Higashihara E (2018) DETECTION OF MICROMETASTATIC PROSTATE CANCER CELLS IN THE LYMPH NODES BY REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION IS PREDICTIVE OF BIOCHEMICAL RECURRENCE IN PATHOLOGICAL STAGE T2 PROSTATE CANCER.Journal of Urology, VOL. 163, NO. 4, (1183-1188), Online publication date: 1-Apr-2000. (2018) EDITORIAL COMMENTJournal of Urology, VOL. 161, NO. 5, (1448-1448), Online publication date: 1-May-1999. Volume 161Issue 4April 1999Page: 1070-1076 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.MetricsAuthor Information CHUNG-LING GAO More articles by this author ROBERT C. DEAN More articles by this author ANGELA PINTO More articles by this author RENEE MOONEYHAN More articles by this author ROGER R. CONNELLY More articles by this author DAVID G. McLEOD More articles by this author SHIV SRIVASTAVA More articles by this author JUDD W. MOUL More articles by this author Expand All Advertisement PDF downloadLoading ...