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Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial
Author(s) -
Bruno Silvia,
Torrisi Rosalba,
Costantini Massimo,
Baglietto Laura,
Fontana Vincenzo,
Gatteschi Beatrice,
Melioli Giovanni,
Nicolo Guido,
Curotto Antonio,
Malcangi Bruno,
Bruttini Gian Paolo,
Varaldo Marco,
Bruzzi Paolo,
Decensi Andrea
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000201)76:2<311::aid-jcb14>3.0.co;2-a
Subject(s) - flow cytometry , cytology , bladder cancer , fenretinide , biomarker , cytometry , pathology , cancer , urine cytology , population , medicine , biology , oncology , immunology , cell culture , retinoid , retinoic acid , biochemistry , environmental health , genetics
Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra‐individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper‐Diploid‐Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle‐invasive bladder cancer, indicating the “low‐risk” features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis. J. Cell. Biochem. 76:311–321, 1999. © 1999 Wiley‐Liss, Inc.