Sensitive reverse transcriptase-polymerase chain reaction-based techniques for detection of epithelial antigen expression, such as cytokeratin 19, in the peripheral blood mononuclear fraction of prostate cancer patients may allow the detection of tumor progression at A molecular level.
Methods
We studied cytokeratin 19 expression by reverse transcriptase-polymerase chain reaction in peripheral blood mononuclear cell samples of 10 control men and serially in 44 patients with prostate cancer every three months for 18 months.
Results
None of the 10 normal control men expressed cytokeratin 19 in their peripheral blood mononuclear fraction. In the patients, cytokeratin 19 positivity at entry was not associated with age, Gleason score, clinical stage, prostate-specific antigen or alkaline phosphatase. Interestingly, having at least one positive cytokeratin 19 result during follow-up correlated significantly with time to prostate-specific antigen progression (P = 0.049), especially in the subgroup of metastatic patients (P = 0.032).
Conclusions
We conclude that cytokeratin 19 expression by reverse transcriptase-polymerase chain reaction in the peripheral blood mononuclear cell fraction of prostate cancer patients correlates with time to prostate-specific antigen progression. Further studies are needed to confirm these findings.
GrassoY.Z., GuptaM.K., LevinH.S., ZippeC.D., KleinE.A.: Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in prostate cancer patients: correlation with pathological stage. Cancer Res, 58: 1456–1459, 1998.
2.
SchmidtB., AnastasiadisA.G., SeifertH.H., FrankeK.H., OyaM., AckermannR.: Detection of circulating prostate cells during radical prostatectomy by standardized PSMA RT-PCR: association with positive lymph nodes and high malignant grade. Anticancer Res, 23: 3991–3999, 2003.
3.
SeidenM.V., KantoffP.W., KrithivasK., PropertK., BryantM., HaltomE., GaynesL., KaplanI., BubleyG., DeWolfW.: Detection of circulating tumor cells in men with localized prostate cancer. J Clin Oncol, 12: 2634–2639, 1994.
4.
ShariatS.F., KattanM.W., SongW., BernardD., GottengerE., WheelerT.M., SlawinK.M.: Early postoperative peripheral blood reverse transcription PCR assay for prostate-specific antigen is associated with prostate cancer progression in patients undergoing radical prostatectomy. Cancer Res, 63: 5874–5878, 2003.
5.
ShariatS.F., GottengerE., NguyenC., SongW., KattanM.W., AndenoroJ., WheelerT.M., SpencerD.M., SlawinK.M.: Preoperative blood reverse transcriptase-PCR assays for prostate-specific antigen and human glandular kallikrein for prediction of prostate cancer progression after radical prostatectomy. Cancer Res, 62: 5974–5979, 2002.
6.
BiancoF.J.Jr., PowellI.J., CherM.L., WoodD.P.Jr.: Presence of circulating prostate cancer cells in African American males adversely affects survival. Urol Oncol, 7: 147–152, 2002.
7.
KantoffP.W., HalabiS., FarmerD.A., HayesD.F., VogelzangN.A., SmallE.J.: Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in men with hormone-refractory prostate cancer. J Clin Oncol, 19: 3025–3028, 2001.
8.
MejeanA., VonaG., NalpasB., DamotteD., BrousseN., ChretienY., DufourB., LacourB., BrechotC., Paterlini-BrechotP.: Detection of circulating prostate derived cells in patients with prostate adenocarcinoma is an independent risk factor for tumor recurrence. J Urol, 163: 2022–2029, 2000.
9.
ThiounnN., SaportaF., FlamT.A., PagesF., ZerbibM., VieillefondA., MartinE., DebreB., ChevillardS.: Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases. Urology, 50: 245–250, 1997.
10.
LintulaS., StenmanU.H.: The expression of prostate-specific membrane antigen in peripheral blood leukocytes. J Urol, 157: 1969–1972, 1997.
11.
LlanesL., FerrueloA., PaezA., GomezJ.M., MorenoA., BerenguerA.: The clinical utility of the prostate specific membrane antigen reverse-transcription/polymerase chain reaction to detect circulating prostate cells: an analysis in healthy men and women. BJU Int, 89: 882–885, 2002.
12.
BartekJ., BartkovaJ., Taylor-PapadimitriouJ., RejtharA., KovarikJ., LukasZ., VojtesekB.: Differential expression of keratin 19 in normal human epithelial tissues revealed by monospecific monoclonal antibodies. Histochem J, 18: 565–575, 1986.
13.
ManhaniA.R., ManhaniR., SoaresH.P., BenditI., LopesF., NicolettiA.G., FonsecaF.L., NovaesM., ZattaS.M., AriasV., GiraltS., del GiglioA.: CK-19 expression by RT-PCR in the peripheral blood of breast cancer patients correlates with response to chemotherapy. Breast Cancer Res Treat, 66: 249–254, 2001.
14.
KrismannM., TodtB., SchroderJ., GareisD., MullerK.M., SeeberS., SchutteJ.: Low specificity of cytokeratin 19 reverse transcriptase-polymerase chain reaction analyses for detection of hematogenous lung cancer dissemination. J Clin Oncol, 13: 2769–2775, 1995.
15.
KanedaT., HoshiS., MaoH., TakahashiT., SuzukiK., SatoM.: Detection of urogenital malignant cells in the peripheral blood by nested RT-PCR using keratin 19 mRNA. Nippon Hinyokika Gakkai Zasshi, 89: 33–42, 1998.
16.
DattaY.H., AdamsP.T., DrobyskiW.R., EthierS.P., TerryV.H., RothM.S.: Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol, 12: 475–482, 1994.
17.
LinY.C., ChenS.C., HsuehS., LoY.F., Chow-WuY.H., LiawI.C., ChengA.J.: Lack of correlation between expression of human mammaglobin mRNA in peripheral blood and known prognostic factors for breast cancer patients. Cancer Sci, 94: 99–102, 2003.
18.
Martinez-PineiroL., RiosE., Martinez-GomarizM., PastorT., de CaboC.M., PicazoM.L., PalaciosJ., PeronaR.: Molecular staging of prostatic cancer with RT-PCR assay for prostate-specific antigen in peripheral blood and lymph nodes: comparison with standard histological staging and immunohistochemical assessment of occult regional lymph node metastases. Eur Urol, 43: 342–350, 2003.
SoaresH.P., Del GiglioA., ClarkO., KumarA., DjulbegovicB.: Reverse transcriptase polymerase chain reaction for minimal residual disease detection in the peripheral blood of women with breast cancer: a meta-analysis. Proc ASCO, 22: 878, 2004.
21.
NovaesM., BenditI., GaricocheaB., Del GiglioA.: Reverse transcriptase-polymerase chain reaction analysis of cytokeratin 19 expression in the peripheral blood mononuclear cells of normal female blood donors. Mol Pathol, 50: 209–211, 1997.
