Prognostic significance of nuclear DNA content and S-phase fraction by flow cytometry in primary papillary superficial bladder cancer

Abstract

This study is aimed at determining the usefulness of nuclear DNA content and S-phase fraction (SPF) to predict tumor recurrence in papillary superficial bladder cancer. Tumor DNA content and SPF were measured by flow cytometry on formalin-fixed, paraffin-embedded tissue from 199 newly diagnosed pTa/pT1 transitional cell carcinomas of patients enrolled into a multicenter prospective study from 1990 to 1992. The follow-up extended up to March 1994, and, at last follow-up, 122 (61.3%) patients have experienced at least one recurrence. After exclusion of 34 cases, whose coefficient of variation exceeded 8%, 131 (79.4%) tumors were diploid, and 34 (20.6%) were aneuploid. There was no association between tumor DNA content and time to first recurrence. Diploid tumors with low SPF (<11%) tended to have a longer recurrence-free survival (RFS) than those with high SPF, but this difference did not reach statistical significance ( P = .2833). SPF in aneuploid tumors did not add any new information. Aneuploidy was associated with higher stage ( P < .001), poorer grade ( P < .002), multifocality ( P= .028), Her-2/neu ( P= .021), and p53 ( P = .033) expression. High SPF correlated with higher stage ( P = .066) and higher grade ( P = .025). This study shows that DNA-ploidy and SPF measured on a single superficial bladder cancer specimen are not predictive of tumor recurrence. The frequent multifocality of the disease may explain, in part, these findings.