Flow Cytometric Analysis of Primary and Metastatic Bladder Cancer

Abstract

A total of 22 patients with high grade P2-4N+ transitional cell carcinoma of the bladder underwent flow cytometric analysis of nuclei obtained from paraffin embedded specimens from the primary (bladder) and metastatic (lymph node) sites. Tumor heterogeneity was defined as polyclonal aneuploidy of the primary tumor (not identified in the population studied) or as a difference in the deoxyribonucleic acid index of the primary and metastatic sites of 0.20 or more (8 patients). With these criteria 8 patients (36%) had heterogeneous tumors and 14 (64%) had homogeneous tumors. The median survival of 14 patients with aneuploid and 8 with diploid primary tumors was 17.5 and 8.0 months, respectively (p equals 0.08, Lee-Desu test). When patient survival was compared to the ploidy of the metastatic site, or in patients with diploid primary and metastatic lesions versus deoxyribonucleic acid aneuploidy at either the primary and/or metastatic site, the aneuploid tumors had a longer survival but this difference was not significant (p equals 0.13 and 0.23, respectively). Our study demonstrates the value of flow cytometry to identify primary metastatic tumor heterogeneity. It also suggests that the presence of metastasis may be a more important factor to define the biological potential of transitional cell carcinoma than is deoxyribonucleic acid ploidy.

Intratumoral Heterogeneity in DNA Ploidy of Bladder Carcinomas

“…data]. Even though Badalament et al [4] examined only highgrade T C C , the incidence o f D N A aneuploidy was 63.6%. In contrast, it was 88.9% in the present investigation.…”

“…The term 'D N A heterogeneity' has been used to de scribe the presence o f two or more D N A stem lines [11], It has been considered that tumors with multiple subpopula tions constitute a minority [12]. Badalament et al [4] re ported that the incidence o f polyclonal aneuploidy in pa tients with aneuploid carcinoma was 57% (8/14) in highgrade T C C o f the bladder. It was much lower than the fre quency in our series (87.5%), although the number ofcases examined in both series was small.…”

“…In the last decade, flow-cytometric D N A analy sis has been used as an effective tool for detecting and monitoring carcinomas o f the urinary bladder [1], A ctu ally, it has shown good correlation o f D N A ploidy with tumor stage and patient survival rate in bladder car cinomas [2][3][4]. However, there are considerable exception al cases.…”

“…Intratumoral difference in D N A ploidy, which may be directly related to tumor cell heterogeneity, has to be investigated in bladder carcinomas prior to establish ment o f correlation between D N A ploidy and clinical data. In carcinomas o f other organs, the frequency of D N A aneuploidy increased as the number o f samples ex amined increased [5 7] and, furthermore, regional differ ence in D N A ploidy in the same tumor has also been re ported [4][5][6][7][8]. It has not yet been studied whether D N A ploidy measured for a specimen from a single area o f a tumor is representative o f the entire tumor.…”

Bladder Transitional Cell Carcinomas: A Comparative Study of Washing and Tumor Bioptic Samples by DNA Flow Cytometry and FISH Analyses

“…Analysis of DNA flow cytometry has been widely utilized in studies of bladder TCCs on histological and cytological specimens [10, 11, 12, 13, 14]. The maximal utility was demonstrated in superficial G 2 tumors for monitoring intravesical therapy, in calculating the risk of progression [3]and in longitudinally following patients with bladder cancer [15].…”