Comparison of quantitative and classic prognosticators in urinary bladder carcinoma

Abstract

The prognostic value of nuclear morphometry and DNA flow cytometry of paraffin embedded material of 58 patients with primary and untreated transitional cell carcinoma of the bladder was compared with that of histological grade (WHO-system), tumour stage (TNM-classification), tumour size, multiplicity and ulceration. Small nuclear size (mean nuclear area less than or equal to 95 microns2) (n = 25) and DNA diploidy (n = 28) indicated a favourable outcome (5-year survival 95.8% and 92.2%); large nuclei (mean nuclear area greater than 95 microns2) (n = 33) and DNA aneuploidy (n = 30) indicated a worse prognosis (5-year survival 61.4% and 62.5%) (Mantel-Cox; p = 0.002 and p = 0.007). The quantitative techniques had the advantage over subjective histological grading that distinguishment of an intermediate patient group (WHO-system: grade 2; n = 32) with heterogeneous outcome (5-year survival 78%) was avoided. Multivariate analysis showed tumour stage as the most important prognosticator of survival. Neither the quantitative techniques, nor the other classic features added significantly to the prediction. The additional value of the quantitative techniques was however shown in superficial carcinoma (TNM-classification: stage Ta and T1; n = 37); large nuclei (mean nuclear area greater than 95 microns2) (n = 15) and aneuploid DNA peaks (n = 13) were associated with progressive recurrent tumour (n = 7) (Mantel-Cox: p = 0.03 and p = 0.0004). The quantitative methods thus indicate which patients are at risk for progression and may enable more appropriate treatment at an earlier stage of disease.

Prognostic Value of MIB-1 Score, p53, EGFr, Mitotic Index and Papillary Status in Primary Superficial (Stage pTa/T1) Bladder Cancer: A Prospective Comparative Study

“…This leaves the clinician with a large group of patients with a variable prognosis and uncertainty regarding the therapeutic strategy. Therefore, a number of two-grade systems have been presented for TCC that are based on flow cytometry [20, 21, 22]or morphometry [22]. Carbin et al [23]presented a modified Bergkvist grading system, including subjective and quantitative elements, which correlated well with the prognosis.…”

“…Methods that have been used to measure cell proliferation, so far, include flow cytometry [20, 22], mitotic indices [24], Ki-67 immunostaining, bromodeoxyuridine incorporation [25], proliferating cell nuclear antigen expression and nucleolar organizer regions [13, 26]. According to Lipponen et al [24], the M/V index appeared to be the best histological prognostic factor in SBC [24].…”

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

“…Unsolved ques tions of tumor heterogeneity (the S phase is very sensitive to this) as well as the lack of compatibility due to various arithmetic algorithms would make further subdivision into possible risk groups rather more difficult and prevent clinical routine use. For progression the majority of studies show staging as the most important parameter [9,75] followed by the growth form of tumor which was used in fewest publica tions [75] as a variable. Assuming that histological grad ing is a subjective method, the DI was proven to be a fur ther independent variable which was superior to all mor phometric parameters [9,72], Within the stages the DI was the most important parameter for progression [84], Replacing proven histological parameters such as stag ing, but less so grading, was not reached and not re quested.…”

“…For progression the majority of studies show staging as the most important parameter [9,75] followed by the growth form of tumor which was used in fewest publica tions [75] as a variable. Assuming that histological grad ing is a subjective method, the DI was proven to be a fur ther independent variable which was superior to all mor phometric parameters [9,72], Within the stages the DI was the most important parameter for progression [84], Replacing proven histological parameters such as stag ing, but less so grading, was not reached and not re quested. However, at least for some problematic patients with bladder tumors treated by surgical therapy alone, secure clues for disease progression can be given.…”

Argyrophilic Nucleolar Organiser Regions in Transitional Cell Bladder Tumours Related to Established Prognostic Factors, Progression and Independent Prognostic Value

“…DNA flow cytometry [1][2][3][4], nuclear morphometry [1,3,5,6], mitotic indexes [6,7], blood group antigens [2], nucleolar organiser regions (Ag-NORs) [8][9][10] and oncogens or their protein products [11] have been tested to find new predictors in place for conventional subjective histological assessments [12,13], Many of the above presented variables are interrelated [ 14] and describe proliferative activity of cancer cells and their prognostic value is propably mediated through this cor relation. Most of the studies using quantitative methods have tested DNA flow cytometry to assess malignancy of TCC.…”