Prognostic value of combined "triple"-reverse transcription-PCR analysis for prostate-specific antigen, human kallikrein 2, and prostate-specific membrane antigen mRNA in peripheral blood and lymph nodes of prostate cancer patients

Clin Cancer Res. 2004 Sep 1;10(17):5808-14. doi: 10.1158/1078-0432.CCR-1004-03.

Abstract

Purpose: We present the largest study of both peripheral blood and lymph node samples examining the utility of reverse transcription-polymerase chain reaction (RT-PCR) for established molecular markers as a diagnostic tool in the molecular staging of prostate cancer patients undergoing radical prostatectomy.

Experimental design: Peripheral blood from 358 patients was obtained before radical prostatectomy. Corresponding obturatory lymph node samples were collected from 153 of these patients. Nested RT-PCR for prostate-specific antigen (PSA), human kallikrein 2 (hK2), and prostate-specific membrane antigen (PSMA) were performed on cDNA from peripheral blood. The lymph node cDNA was analyzed for PSA und hK2 expression.

Results: RT-PCR in peripheral blood was positive in 124 (34.6%) of 358 samples for PSA, 215 (60.1%) of 358 for PSMA, and 97 (27.1%) of 358 for hK2. Comparison of positive RT-PCR rates of pT(2) and pT(3) tumors in corresponding peripheral blood for PSA, PSMA, and hK2 were 31.9 and 40.0%, 58.8 and 62.5%, and 26.9 and 27.5%, respectively. Histopathologically, cancer-free lymph node samples were positive in RT-PCR for PSA and hK2 in 70 (49.6%) of 141 and 89 (63.2%) of 141 of cases. All histologically positive lymph node samples (n = 12, pN+) were positive for PSA RT-PCR. PSA RT-PCR alone, as well as combined PSA/PSMA RT-PCR evaluation, in peripheral blood showed a significant association with grading. PSA RT-PCR lymph node-negative samples were significantly less likely positive in their corresponding peripheral blood RT-PCR sample.

Conclusions: Although the preoperative PSA RT-PCR in peripheral blood correlated with the grading of prostate cancer, no combination of RT-PCR results using "triple" markers (PSA, hK2, PSMA) in peripheral blood and/or lymph nodes yielded additional preoperative staging information.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / blood
  • Antigens, Surface / genetics*
  • Case-Control Studies
  • DNA, Complementary / genetics
  • Glutamate Carboxypeptidase II / blood
  • Glutamate Carboxypeptidase II / genetics*
  • Humans
  • Lymph Nodes / metabolism*
  • Male
  • Neoplasm Staging
  • Prognosis
  • Prostate / metabolism
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / genetics*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / blood*
  • RNA, Neoplasm / blood
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Tissue Kallikreins / blood
  • Tissue Kallikreins / genetics*
  • Tumor Cells, Cultured

Substances

  • Antigens, Surface
  • DNA, Complementary
  • RNA, Messenger
  • RNA, Neoplasm
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Tissue Kallikreins
  • Prostate-Specific Antigen