Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer

R Thuret, K Chantrel-Groussard, A-R Azzouzi, J-M Villette, S Guimard, P Teillac, P Berthon, A Houlgatte, A Latil, O Cussenot, R Thuret, K Chantrel-Groussard, A-R Azzouzi, J-M Villette, S Guimard, P Teillac, P Berthon, A Houlgatte, A Latil, O Cussenot

Abstract

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml(-1), prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT-PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies.

References

    1. Berthon P, Valeri A, Cohen-Akenine A, Drelon E, Paiss T, Wohr G, Latil A, Millasseau P, Mellah I, Cohen N, Blanche H, Bellane-Chantelot C, Demenais F, Teillac P, Le Due A, de Petriconi R, Hautmann R, Chumakov I, Bachner L, Maitland NJ, Lidereau R, Vogel W, Fournier G, Mangin P, Cussenot O (1998) Predisposing gene for early-onset prostate cancer, localized on chromosome lq42.2–43. Am J Hum Genet 62: 1416–1424
    1. Brawer MK (1999) Prostate-specific antigen: current status. CA Cancer J Clin 49: 264–281
    1. Cairns P, Esteller M, Herman JG, Schoenberg M, Jeronimo C, Sanchez-Cespedes M, Chow NH, Grasso M, Wu L, Westra WB, Sidransky D (2001) Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. Clin Cancer Res 7: 2727–2730
    1. Catalona WJ, Beiser JA, Smith SD (1997) Serum free prostate specific antigen and prostate specific antigen density measurements for predicting cancer in men with prior negative prostatic biopsies. J Urol 158: 2162–2167
    1. Catalona WJ, Partin AW, Slawin KM, Naughton CK, Brawer MK, Flanigan RC, Richie JP, Patel A, Walsh PC, Scardino PT, Lange PH, deKernion JB, Southwick PC, Loveland KG, Parson RE, Gasior GH (1998) Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 279: 1542–1547
    1. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162: 156.
    1. Cussenot O, Teillac P, Berthon P, Latil (2001) A Noninvasive detection of genetic instability in cells from prostatic secretion as a marker of prostate cancer. Eur J Int Med 12: 17–19
    1. Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, Lathrop M, Gyapay G, Morissette J, Weissenbach J (1996) A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 380: 152–154
    1. Dong JT, Chen C, Stultz BG, Isaacs JT, Frierson Jr HF (2000) Deletion at 13q21 is associated with aggressive prostate cancers. Cancer Res 60: 3880–3883
    1. Elo JP, Visakorpi T (2001) Molecular genetics of prostate cancer. Ann Med 33: 130–141
    1. Fromont G, Joulin V, Chantrel-Groussard K, Vallancien G, Guillonneau B, Validire P, Latil A, Cussenot O (2003) Allelic losses in localized prostate cancer: association with prognostic factors. J Urol 170: 1394–1397
    1. Gao X, Zacharek A, Salkowski A, Grignon DJ, Sakr W, Porter AT, Honn KV (1995) Loss of heterozygosity of the BRCAl and other loci on chromosome 17q in human prostate cancer. Cancer Res 55: 1002–1005
    1. Greenlee RT, Murray T, Bolden S, Wingo PA (2000) Cancer statistics, 2000. CA Cancer J Clin 50: 7–33
    1. Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, Kiemeney LA, Witjes JA, Schalken JA (2003) DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 44: 8–15
    1. Hügel A, Wernert N (1999) Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer. Br J Cancer 79: 551–557
    1. Kibel AS, Faith DA, Bova GS, Isaacs WB (2000) Loss of heterozygosity at 12P12–13 in primary and metastatic prostate adenocarcinoma. J Urol 164: 192–196
    1. Latil A, Bieche I, Pesche S, Volant A, Valeri A, Fournier G, Cussenot O, Lidereau R (1999) Loss of heterozygosity at chromosome arm 13q and RBI status in human prostate cancer. Hum Pathol 30: 809–815
    1. Macintosh CA, Stower M, Reid N, Maitland NJ (1998) Precise microdissection of human prostate cancers reveals genotypic heterogeneity. Cancer Res 58: 23–28
    1. Matsuyama H, Pan Y, Oba K, Yoshihiro S, Matsuda K, Hagarth L, Kudren D, Naito K, Bergerheim US, Ekman P (2001) Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer. Clin Cancer Res 7: 3139–3143
    1. Meid FH, Gygi CM, Leisinger HJ, Bosman FT, Benhattar J (2001) The use of telomerase activity for the detection of prostatic cancer cells after prostatic massage. J Urol 165: 1802–1805
    1. Mohan RR, Challa A, Gupta S, Bostwick DG, Ahmad N, Agarwal R, Marengo SR, Amini SB, Paras F, MacLennan GT, Resnick MI, Mukhtar H (1999) Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans. Clin Cancer Res 5: 143–147
    1. Straub RE, Speer MC, Luo Y, Rojas K, Overhauser J, Ott J, Gilliam TC (1993) A microsatellite genetic linkage map of human chromosome 18. Genomics 15: 48–56
    1. Terris MK (1999) Sensitivity and specificity of sextant biopsies in the detection of prostate cancer: preliminary report. Urology 54: 486–489
    1. Zenklusen JC, Thompson JC, Troncoso P, Kagan J, Conti CJ (1994) Loss of heterozygosity in human primary prostate carcinomas: a possible tumor suppressor gene at 7q31.1. Cancer Res 54: 6370–6373

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera