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Molecular Serological Detection of DNA Alterations in Transitional Cell Carcinoma Is Highly Sensitive and Stage Independent

Department of Urology, Philipps-University Marburg Medical School, Marburg, Germany

Purpose: To evaluate the efficacy of fluorescent microsatellite analysis (MSA) for the serological diagnosis of transitional cell carcinoma (TCC) of the urinary tract analyzing free tumor DNA in the serum of cancer patients.

Experimental Design: We applied fluorescent MSA to detect serum–DNA alterations in patients suffering from bladder and upper urinary tract TCC and prospectively collected fresh tumor, peripheral blood, and serum specimens from 61 consecutive patients to obtain the corresponding DNA. Fluorescent MSA was performed with a total of 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q, and 20q in the 61 cancer patients, as well as in 20 healthy controls.

Results: Molecular serological analysis led to tumor-specific diagnosis of TCC in 80.3% (49 of 61) of cases. Four healthy controls displayed serum–DNA artifacts rendering a specificity of 80%. The highest frequency of serum–DNA alterations was detected for chromosomal region 8p with 36%. Chromosomes 5q, 9p, and 20q showed serum–DNA alterations in 18 to 21%. The identification of serum–DNA alterations was not statistically associated with underlying local tumor stage (P = 0.29) but was more frequent in high-grade tumors (P = 0.08).

Conclusions: MSA offers a highly sensitive method for serological diagnosis of TCC. To optimize specificity, simultaneous analysis of tumor DNA is advised to rule out artifacts resembling allelic imbalance in MSA of serum DNA.

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				R. V. KNOBLOCH, H. BRANDT, and R. HOFMANN Molecular Serological Diagnosis in Transitional Cell Bladder Cancer Ann. N.Y. Acad. Sci., June 1, 2004; 1022(1): 70 - 75. [Abstract] [Full Text] [PDF]