Cellular DNA Content and Proliferative Activity Evaluated by Flow Cytometry versus Histopathological and Staging Classifications in Human Bladder Tumors

Vita, R. De; Forte, D.; Maggi, Federica; Eleuteri, Patrizia; Silverio, F. Di

doi:10.1159/000473582

Cited by 14 publications

(4 citation statements)

References 15 publications

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“…From Table 2 and Figure 3 we can conclude that there is a positive correlation between DI, SPF, SPF+G 2 /M and the tumor grade, contrary to the results observed by Lipponen et al (36) but in agreement with the results reported by De Vita et al (35). In different types of tumors, the proliferative activity measured as SPF has been used more frequently than SPF+G 2 M, apparently because it gives better results (12,19,21,37).…”

Section: Discussionsupporting

confidence: 69%

Comparison of Urine Cell Characteristics by Flow Cytometry and Cytology in Patients Suspected of Having Bladder Cancer

Barlandas-Rendón¹,

Müller²,

Garcı́a-Latorre³

et al. 2002

Clinical Chemistry and Laboratory Medicine

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The diagnosis of bladder cancer is confirmed by histological analysis of tissue biopsies. Cytology of urine samples is a noninvasive alternative. The aim of this work was to find out whether flow cytometry of urine samples is more sensitive than cytology. For this purpose we studied 115 patients suspected of having bladder cancer. Cells isolated from urine samples were analyzed by cytometry for the expression of cytokeratin and CD 45 and for DNA measurements such as: DNA index, synthesis phase fraction and proliferative index (SPF + G2/M phase). At the same time we carried out cytological analysis. All positive cases were confirmed by histology (21/115), 18 were diagnosed by flow cytometry and 16 by cytology, with a sensitivity of 85.7% and 76.1%, respectively. Two cases were found to be positive by flow cytometry, which were not confirmed by histology, while no false positives were detected by cytology. We found that both techniques gave almost identical results for the diagnosis of bladder cancer, although there were differences in non-malignant samples. In conclusion, flow cytometry is slightly more sensitive than cytology but the combination of the two techniques improves the diagnosis.

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Section: Discussionsupporting

confidence: 69%

Comparison of Urine Cell Characteristics by Flow Cytometry and Cytology in Patients Suspected of Having Bladder Cancer

Barlandas-Rendón¹,

Müller²,

Garcı́a-Latorre³

et al. 2002

Clinical Chemistry and Laboratory Medicine

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“…Although current histopathological and cytogenetic methods can provide some prognostic information (Dahiya and Deng, 1998;De Vita et al, 1991), relatively little is known about molecular genetic alterations or dysfunctions of DNA repair machinery, leading to tumor development and progression.…”

mentioning

confidence: 99%

Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies

Pucci¹,

Mazzarelli

Rabitti

et al. 2001

Oncogene

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The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein kinase (DNA-PK) and its DNAbinding activity mediates DNA double-strand breaks repair. Although Ku80 was recently proposed as a caretaker gene involved in the control of genome integrity, no data are available on Ku70/80 DNAbinding activity in human tumors. Heterodimer DNAbinding activity and protein expression were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder primary tumors and three metastatic nodes from breast cancers. Corresponding normal tissues of the same patients were used as controls. Ten out of 15 tumors showed nuclear Kubinding activity 3 ± 10 times higher than in the normal tissues, irrespective of bladder or breast origin. Conversely, in 5/15 primary tumors and in all the metastatic nodes analysed, nuclear Ku-activity was 1.5 ± 4.5-fold lower than in the corresponding normal tissues. Cytoplasmic heterodimer activity signi®cantly diered between tumor and normal tissues, displaying a 2 ± 10-fold increase in neoplastic tissues. Three dierent patterns combining both Ku expression and activity with tumor characteristics were identi®ed. In low aggressive breast tumors p70/p80 proteins were expressed in tumor but not in normal tissues. The heterodimer bindingactivity matched the protein levels. In non-invasive bladder carcinomas no signi®cant dierences in protein expression between tumor and the corresponding normal tissues were found, however heterodimer binding-activity was increased in tumor samples. In breast and bladder tumors, at the advanced stage and in node metastases, the binding activity was strongly reduced in tumor biopsies, however no dierences were demonstrated between normal and tumor protein levels. Our results suggest a dierent modulation of Ku70/80 DNA-binding activity in human neoplastic tissues, possibly related to tumor progression. Findings provide further data on tissue-speci®c protein expression and post-translational regulation of heterodimer activity. Oncogene (2001) 20, 739 ± 747.

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“…In the high-risk group of >15% only 14% of patients survived the period of follow-up. In a more recent investigation deVita et al [30] [38], the independence of this prognostic information is not secured, on the contrary the correlation to histological parameters and aneuploidy, which is less liable to distur bances, almost entirely explains the prognostic differ ences found. The clinically relevant question, whether within the large group of diploid tumors a prospective prediction about recurrence frequency is possible with proliferation rate, cannot be answered due to the small differences in proliferation.…”

Section: Tumor Stadiummentioning

confidence: 84%

“…12). From the purely 30 Lied DNA histogram analysis to the DNA/cytokeratin method, diagnostic gain amounts to 10% resulting in 49%. This could, however, be raised further when including prolifer ation.…”

Section: Dna/cytokeratin Measurements Of Cells Were Com Pared To Cytomentioning

confidence: 99%

Flow Cytometric DNA/ Cytokeratin Analysis of Bladder Lavage: Methodical Aspects and Clinical Implications

Liedl

1995

Urol Int

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Over the last few years cytological investigations of bladder lavage have gained ever-increasing importance in the diagnosis and follow-up of bladder tumors. Flow cytometric DNA analysis is searching for more objective ways to characterize tumor tissue beyond its morphological differentiation. Since the end of 1987 more than 400 bladder lavages have been analyzed both cytologically and by multiparameter flow cytometry. DNA/cytokeratin-8,18 antibody labelling of methanol-fixed single cells provides a standardized method which is not liable to disturbances and enables use in a routine laboratory. Aneuploidy was divided in several subgroups according to the DNA index. Proliferation of the urothelial population as a diagnostic parameter was investigated. Multiparameter flow cytometric measurement can identify and assess all subpopulations of bladder lavage such as inflammatory cells, squamous cells and squamous cell metaplasia. Cytokeratins enable a selective examination of the urothelial population after gating; the diagnostic accuracy for aneuploid tumor stem lines is markedly increased when compared to single-parameter DNA analysis. Higher specificity is reached by excluding falsely positive ‘aneuploid’ squamous cells; higher sensitivity is made possible by lowering the limit of detection for actual aneuploidy within a specimen, especially for near-diploid and tetraploid carcinomas. When compared to cytological malignancy grading, the aneuploidy rate is 26% in G1/2 tumors, 42% in G2 and 78% in G3 tumors (p < 0.005). More than half of the aneuploid bladder lavages with a negative or suspect cytology were diagnosed as tumor recurrences either histologically or cytologically in the following year. Moderately differentiated carcinomas with an aneuploid DNA distribution had a higher rate of recurrence than tumors with euploid distributions when treated curatively by organ-conserving therapy. DNA/cytokeratin analysis of bladder lavage enables an artefact-free measurement of tumor criterium aneuploidy; this is more specific and less sensitive than cytology. Due to the lack of separability of urothelial proliferation in euploid specimens, the aim to make flow cytometry a method equaling cytology cannot be reached. Therefore, the greatest value of flow cytometry is not in tumor screening, but in reliable detection of highly malignant aneuploid tumors at initial diagnosis, during therapy and recognition of recurrence of superficial bladder carcinomas. Reviewing the literature, flow cytometrically proven aneuploidy, especially triploid tumor stemlines, can be used to predict possible invasive growth. DNA/cytokeratin measurements are hence indicated when an exact assessment of prognosis can influence the therapeutic procedures.

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Cellular DNA Content and Proliferative Activity Evaluated by Flow Cytometry versus Histopathological and Staging Classifications in Human Bladder Tumors

Cited by 14 publications

References 15 publications

Comparison of Urine Cell Characteristics by Flow Cytometry and Cytology in Patients Suspected of Having Bladder Cancer

Comparison of Urine Cell Characteristics by Flow Cytometry and Cytology in Patients Suspected of Having Bladder Cancer

Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies

Flow Cytometric DNA/ Cytokeratin Analysis of Bladder Lavage: Methodical Aspects and Clinical Implications

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