Molecular serological diagnosis in transitional cell bladder cancer.
There are no reliable serological tumor markers for transitional cell carcinoma (TCC) of the urinary bladder. Fluorescent microsatellite analysis (MSA) was used to detect serum-DNA alterations in patients with bladder cancer. Prospectively, fresh tumor-, peripheral blood-, and serum-specimens were collected from 58 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. DNA was extracted by the phenol-chloroform method from tumors and blood lymphocytes. Serum DNA was isolated by a commercial kit. Fluorescent MSA was performed with a total of 17 polymorphic markers from chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q, and 20q in the 58 cancer specimens as well as in specimens from 20 healthy controls. Detection of allelic imbalance and loss of heterozygosity in the tumor and serum specimens was carried out on an automated laser sequencer. Serum-DNA alterations were identified in 79.3% (46/58). Four healthy controls displayed serum-DNA artefacts rendering a specificity of 80%. The highest frequency of serum-DNA alterations (38%) was detected for chromosomal region 8p. Chromosomes 5q, 9p, and 20q showed serum-DNA alterations in 20% to 23%. Identification of tumor-specific serum-DNA alterations was stage independent (P >0.05), but was more frequent in high-grade tumors (P = 0.08). To optimize specificity, simultaneous analysis of tumor DNA is advised to rule out artefacts resembling allelic imbalance in MSA of serum DNA. The method then has potential for application as a "serological marker" in the follow-up of patients after radical surgical therapy for invasive TCC of the bladder.
von Knobloch
Rolf
R
Department of Urology, Philipps-University Marburg Medical School, Marburg, Germany. Rolf.von-Knobloch@med.uni-marburg.de
Brandt
Heidrun
H
Hofmann
Rainer
R
D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000097:blood* / Q000302:isolation & purification; D005456:Fluorescent Dyes; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; D005456:Fluorescent Dyes