Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial

Silvia Bruno, Rosalba Torrisi, Massimo Costantini, Laura Baglietto, Vincenzo Fontana, Beatrice Gatteschi, Giovanni Melioli, Guido Nicolo, Antonio Curotto, Bruno Malcangi, Gian Paolo Bruttini, Marco Varaldo, Paolo Bruzzi, Andrea Decensi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)311-321
Number of pages11
JournalJournal of Cellular Biochemistry
Volume76
Issue number2
DOIs
Publication statusPublished - 1999

Fingerprint

Flow cytometry
Chemoprevention
Biomarkers
Urinary Bladder Neoplasms
Cytology
Flow Cytometry
Cell Biology
DNA
Urinary Bladder
Washing
Ploidies
Diploidy
Tumors
Epithelial Cells
Fenretinide
Recurrence
Time and Motion Studies
Retinoids
Cell proliferation
Aneuploidy

Keywords

  • Biomarker
  • Bladder cancer
  • DNA flow cytometry

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial. / 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.

In: Journal of Cellular Biochemistry, Vol. 76, No. 2, 1999, p. 311-321.

Research output: Contribution to journalArticle

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. / Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial. In: Journal of Cellular Biochemistry. 1999 ; Vol. 76, No. 2. pp. 311-321.
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AU - Fontana, Vincenzo

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