Independent clinical, histological and quantitative prognostic factors in transitional‐cell bladder tumours, with special reference to mitotic frequency

Abstract

A cohort of 537 transitional-cell bladder cancers (TCC) was followed up for a mean of 9 years. Clinical stage, WHO grade, papillary status, 6 nuclear factors and volume-corrected mitotic index (M/V index) were related to progression and survival. Classic and quantitative prognostic factors were significantly interrelated (p less than 0.001). In Ta-Tl tumours M/V index predicted progression independently (p less than 0.001) and in the entire cohort progression was related independently to the M/V index (p = 0.0001) and to the WHO grade (p = 0.0022). In survival analysis, clinical stage (p less than 0.0001), M/V index (p less than 0.0001), WHO grade (p less than 0.0001), papillary status (p less than 0.0001) and nuclear factors (p less than 0.0001) were significant predictors. In papillary tumours, clinical stage (p less than 0.0001), M/V index (p less than 0.0001), WHO grade (p less than 0.0001) and nuclear factors (p = 0.0001-0.0133) were related to survival. In a multivariate analysis T-category (p less than 0.001), WHO grade (p less than 0.001), M/V index (p = 0.002) and papillary status (p = 0.034) predicted survival independently in the entire cohort whereas in papillary tumours T-category (p less than 0.001) and M/V index (p less than 0.001) were independent predictors. If tumours with pelvic lymph-node metastases or distant metastases at diagnosis were excluded from the analysis, T-category (p less than 0.001), M/V index (p less than 0.001) and WHO grade (p less than 0.001) were independent predictors. In papillary tumours T-category (p less than 0.001), M/V index (p less than 0.001) and WHO grade (p = 0.048) predicted survival. The results emphasize the importance of mitotic activity as a most important histological prognostic factor in TCC, second only to clinical stage. In Ta-TI tumours quantitative mitotic frequency analysis includes all the available independent prognostic information. Accordingly, TCC can be graded by mitotic frequency analysis in place of subjective grading systems.

Evaluation of P53 Protein Overexpression, Ki67 Proliferative Activity and Mitotic Index as Markers of Tumour Recurrence in Superficial Transitional Cell Carcinoma of the Bladder

“…The percentage of stained tumour cell nuclei considered as a positive p53 immunohistochemical pattern has been reported to range from >0% [13, 29]to 65% thresholds [42]. Since the 5 and 20% positive p53 staining levels have been widely used [14, 25, 43], the aim of our study was also to assess if one of these thresholds could be better correlated with tumour outcome.…”

“…The determination of mitotic activity has shown prognostic value in bladder cancer, although all the studies in this area come from one group of researchers [23, 24, 25, 26, 27]. The relationship between p53 protein overexpression and proliferating activity has been assessed by mean of Ki67 LI [28, 29], but not with mitotic index.…”

The value of histoquantitative measurements in prognostic assessment of renal adenocarcinoma

“…The mitotic figures were identified "blind", as described (Baak and Oort, 1983). The volume-corrected mitotic index (M/V index) method was used in evaluating the mitotic frequency as originally described (Haapasalo et at, 1989), and subsequently modified by us (Eskelinen et al, 1992;Lipponen et al, 1992). The M / V index expresses the number of mitotic figures/mm2 of neoplastic epithelium in the microscope image.…”

“…Similarly, stereologically calculated mean nuclear volumes have been evaluated in renal carcinoma (Tosi et al, 1986;Donhuijsen et al, 1991). Although planar morphometry has been tested in several epithelial tumours (Haapasalo et aL, 1989; Lipponen et al., 1990a,b;Eskelinen et al, 1991a Eskelinen et al, ,b, 1992, only limited information is available on the use of this technique for prognostication of renal-cell carcinoma (Tosi et at., 1986;Donhuijsen et al, 1991).Cancer proliferation as determined by mitotic indices has been firmly related to patient survival in several human malignancies (Eskelinen et al, 1991b(Eskelinen et al, , 1992Lipponen et al, 1992), but their applicability in grading renal-cell carcinoma has not been analyzed so far. Recent results using other indicators of cell proliferation (Delahunt et al, 1991;Lipponen et al, 1991a), however, suggest a definite prognostic value for the mitotic indices, which can be measured in routine histopathological sections.…”

Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis

“…The prognosis of transitional cell bladder cancer (TCC) depends on the extent of the primary tumour at diagnosis (Zingg & Wallace, 1985;Lipponen et al, 1992Lipponen et al, , 1993 and its biological characteristics (Neal et al, 1990;Lipponen, 1993a,b;Sarkis et al, 1993). Recent analyses indicate that the proliferation rate of cancer cells is an important factor when the metastatic potential of TCC is evaluated.…”