Search

The immunohistochemical reactivity of a new tumour marker MCA (mucinous carcinoma associated antigen) was determined in human breast cancer. The material consisted of paraffin-embedded biopsies from the breast tumours in 95 patients. The age of the patients at the time of diagnosis was 58.1 +/- 13.1 years. The maximal follow-up time was 13.3 years and the mean follow-up time 12.4 years (range 11.5-13.3 years). MCA positivity was not related to histological type or size of the tumour. It was, however, related to axillary node involvement (p = 0.05) and metastasis (p = 0.06) during the follow-up time. The prediction of metastasis (p = 0.05) and node involvement (p = 0.048) was better in postmenopausal women. Crude survival or breast cancer survival could not be predicted with statistical significance on the basis of MCA staining. The disease-free survival had an almost statistically significant correlation with MCA positivity (p = 0.09). Our results suggest that the new tumour marker antigen MCA reacts with breast cancer cells in paraffin sections. It might be used in identification of cancer cells in tissue sections. MCA can also be used as a weak indicator of aggressiveness of the tumour.

A retrospective study was done including 265 patients with a mean clinical follow-up of 10 years. The mitotic activity in initial bladder tumor biopsies was estimated using two different methods: the traditional mitotic activity index (MAI) and the recently introduced volume-corrected mitotic index (M/V index). The grading results obtained using these indexes were compared to prognostic information obtained by subjective histological grading (WHO) and clinical staging (UICC). The progression of bladder cancer during the follow-up period was significantly related to the M/V index (p less than 0.0001), MAI (p less than 0.0001) and histological grade (p less than 0.0001) in that order. The progression in Ta-T1 tumors was significantly related to the M/V index in univariate and multivariate analysis as well. The recurrence-free period was significantly related to MAI (p = 0.006) and M/V index (p = 0.032). Clinical stage (p less than 0.0001), histological grade (p less than 0.0001), M/V index (p less than 0.0003) and MAI (p less than 0.0001) predicted bladder cancer-related survival. In a multivariate analysis the M/V index predicted the progression and survival better than MAI and gave comparable results to those obtained with subjective histological grading. The results encourage the use of the M/V index in grading bladder cancer in place of MAI.

The nuclear DNA content of archival paraffin-embedded bladder cancer samples (70 patients) of WHO grades I-III has been measured by flow cytometry. The female/male ratio was 15/55. The mean follow-up time was 13 years (range 9.6-22.0 years). 37 of 70 (53%) patients had DNA index 1.0 (diploid DNA content), and the remaining 33 (47%) patients had an aneuploid tumor. There was no significant difference in the age (mean +/- SD) of the patients having a diploid (66 +/- 9 years) or an aneuploid tumor (68 +/- 11 years) at the time of diagnosis. 47 deaths occurred during the follow-up period; 24 (51%) of these were due to bladder cancer (12 diploid, 12 aneuploid tumors). No significant difference was found after radical treatment during the disease-free interval (mean +/- SD) between diploid (48 +/- 45 months) and aneuploid (35.5 +/- 35 months) groups of patients. Recurrences during the follow-up period were equally common among aneuploid and diploid tumors. A statistically significant relation between histological grade and survival could be demonstrated, but DNA ploidy and S phase fraction had little prognostic value in this respect. There was no statistically significant difference in survival between aneuploid (30%) and diploid (35%) groups of tumors during the follow-up period. The study suggests that flow cytometric determination of nuclear DNA ploidy from paraffin-embedded samples in bladder tumors does not add to the prognostic power of subjective histological grading.

A retrospective follow-up (range 9.4-22 years, mean 13 years) study of 83 patients with grade I-III (WHO) bladder carcinomas was performed. Nuclear area (mean +/- SD 59.7 +/- 18.7 microns2) and the SD of nuclear area (mean +/- SD 19.7 +/- 13.4 microns2) were determined by using morphometric methods. The SD of nuclear area and histopathological grade exhibited a clearly significant relation, the relation between grade and nuclear area was weaker. The number of recurrences in the bladder and the recurrence-free period were not significantly related to histopathological grade, mean nuclear area or SD of nuclear area. The progress in nodal or metastatic stage could be predicted by histopathological grade, mean nuclear area and SD of the nuclear area. Prediction of crude survival, however, was not efficient. When only bladder cancer deaths were included in the analysis, histopathological grade (p less than 0.001), mean nuclear area (p = 0.011) and SD of the nuclear area (p = 0.001) showed a significant relation to survival. Grade II tumors could be divided into two prognostically different groups using nuclear area and SD of the nuclear area as classifiers. The results suggest that morphometric parameters are as good as histopathological grade in predicting long-term prognosis of bladder carcinomas, and better than the histopathological grade in predicting progress in nodal (N) or metastatic (M) stage.

The potential of nuclear morphometry and volume-corrected mitotic index (M/V index) in grading cases of transitional cell carcinoma of the urinary bladder was studied. 30 cases of bladder cancer including all three WHO grades were evaluated. Four investigators selected independently the most atypical field from paraffin sections, and one investigator measured the nuclear areas from these fields using the IBAS 1&2 image analyzer system. Following the same sampling rule, four investigators counted the mitotic figures per area of neoplastic tissue in the microscopic image at an objective magnification of X40. The mean nuclear areas covered values from 28.1 to 139.0 microns 2 (mean +/- SD 57.2 +/- 18.9). The total variance of measurements was 359.1 and the mean variance between corresponding fields 110.2 (about 30% of the total variation). The efficiency was evaluated by estimating the fraction of falsely classified cases. Instrumental morphometry of nuclear area in a three-grade system gave an efficiency of 79% and of 90%, in a two-grade system. The M/V index varied from 0 to 54 (mean +/- SD 12.3 +/- 10.9). The total variance was 119.8 and the methodological variance 15.5 (about 13% of total variance). In a three-grade system this would correspond to an efficiency of about 75%; in a two-grade system the efficiency would be 88%. The results suggest that nuclear area and M/V index estimates constitute efficient grading systems in bladder carcinoma.

The immunohistochemical reactivity of tumour markers MCA and CA50 was determined in transitional cell carcinoma of the bladder of WHO grades I-III. The material consisted of paraffin-embedded biopsies from bladder tumors in 83 patients. Mean follow-up time was 13 years (range 9.6-22 years). Staining indexes for the whole section and for the area with maximal staining intensity were calculated (for MCA; IMCAtot, IMCAmax, for CA 50: ICA50tot, ICA50max). Also two combination indexes were created (Itot, Imax). The relations between histological grade on one hand, and IMCAtot (p less than 0.001), IMCAmax (p = 0.007), ICA50tot (p less than 0.001), and ICA50max (p less than 0.001) on the other were statistically significant. IMCAtot (p = 0.008) and ICA50max (p 0.040) had a statistically significant relation to clinical stage. IMCAtot (p = 0.004) and IMCAmax (p = 0.001) also predicted node involvement with statistical significance. Metastasizing behavior could be predicted with all four indexes with statistical significance (IMCAtot p = 0.021; IMCAmax, p = 0.001; ICA50tot, p = 0.021; ICA50max, p = 0.050), but best with IMCAmax. Bladder cancer survival was related to IMCAtot (p = 0.044) and to ICA50tot (p = 0.0009) with statistical significance. The higher the MCA positivity and the lower the CA50 positivity, the worse was the prognosis. The combination index (Itot) predicted survival (p = 0.0004) better than IMCAtot or ICA50tot separately. Itot and Imax did not offer any advantages over other indexes in predicting node involvement or metastasis. Grade II tumors were divided into two prognostic groups using Itot, but the difference between survival was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective clinicopathological study was done of 136 T1 bladder cancer patients, mean follow-up 10 years. With interactive morphometry, mean nuclear area, mean standard deviation of nuclear area (SDNA) and the mean area of the 10 largest nuclei (NA10) were measured in biopsy specimens from primary tumours. Volume corrected mitotic index (M/V index) was estimated in the same sections. Histological grading was done according to WHO and clinical staging according to UICC. Progress in bladder cancer was observed in 26 cases. Progressing tumours had significantly higher M/V values (P = 0.0038) than tumours without progression. By chi 2 statistics NA10 (P = 0.0065) and high M/V index values (P = 0.0104) eventually metastasised. Nuclear area (P = 0.0025), NA10 (P = 0.0053), histological grade (P = 0.0071), NA (P = 0.0563) and M/V index (P = 0.0979) predicted bladder cancer-related survival, in that order. The recurrence rate or recurrence-free period were not related to histological indices. The results suggest the use of these morphometric features instead of histological grading in the prediction of T1 bladder tumours.

The potential of morphometry in grading cases of transitional cell carcinoma of the urinary bladder was evaluated. Thirty cases of bladder cancer including all three WHO grades were studied. Three investigators measured the nuclear areas using the IBAS 1&2 image analyser system. The means, the standard deviations and the variances of the measurements were calculated. The nuclear areas covered values from 25.1 to 107.4 square micrometers, the mean +/- SD being 52.6 +/- 17.5. The total variance of measurements, including biological and methodological variation, was 304.6, and the methodological variance 10.4 (about 3.5% of the total variation). In a 3-grade grading system this would correspond to an efficiency of about 92%, and in a 2-grade system of about 96%, which are the percentages correctly graded by the grading system.