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P K Lipponen

Publications and source records attributed to P K Lipponen.

At least 55 records · Page 3Linked to original sources
PubMed1992

Argyrophilic nucleolar organiser regions in transitional cell bladder tumours related to established prognostic factors, progression and independent prognostic value.

Paraffin-embedded archival biopsy specimens from 229 primary transitional cell carcinomas (TCCs) were stained with silver nitrate to demonstrate the nucleolar organiser regions (Ag-NORs). T3-T4 high grade tumours had higher Ag-NOR counts/nucleus than low grade superficial papillary tumours (p less than 0.001). Non-papillary tumours showed more Ag-NORs than papillary ones (p less than 0.001). Aneuploid tumours with high S phase fraction had more Ag-NORs than diploid tumours (p less than 0.001) and mitotic frequency was also related significantly to Ag-NOR count (p less than 0.001). SD of nuclear area and nuclear area as measured by planar morphometry correlated significantly to Ag-NOR count (p less than 0.001). Close to 60% of the total number of Ag-NORs/nucleus can be related to other quantitative variables. Ag-NORs predicted independently survival in Ta-T1 tumours (p = 0.016) whereas in the whole series Ag-NORs had no independent prognostic value.

Aneuploidy↗
PubMed1991

Progression and survival in transitional cell bladder cancer: a comparison of established prognostic factors, S-phase fraction and DNA ploidy.

DNA flow cytometric (FCM) data, histological features and clinical stage of bladder tumours in 222 patients were related to outcome during a mean follow-up of 10 years. Aneuploidy was detected in 82 (37%) of tumours and 140 (63%) were diploid. Intratumour heterogenity of DNA ploidy was found in 27% of 30 cases. Aneuploidy and high S-phase fraction (SPF) were related to clinical stage, histological grade and papillarity (P less than 0.0001). Aneuploidy (P less than 0.0001) and high SPF (P less than 0.0001) predicted metastasis to pelvic lymph-nodes and to distant sites. T category (P less than 0.0001), SPF (P less than 0.0001), histological grade (P less than 0.0001), papillarity (P = 0.0021), DNA aneuploidy (P = 0.0094) and G2 fraction (P = 0.0340) predicted cancer-related survival. Multivariate analysis showed DNA aneuploidy as the most important predictor of progression in T category (P = 0.0003) and T category was the most important predictor of lymph-node involvement (P = 0.0083) and metastasis (P = 0.0015), followed by FCM parameters. In Ta-T1 tumours SPF predicted progression independently (P = 0.0153). FCM offers more accurate prognostic information in Ta-T1 tumours than conventional methods. In invasive tumours, FCM offers quantitative prognostic information in terms of pelvic lymph-node metastasis and metastasis to distant sites.

Aged↗
PubMed1991

The role of nucleolar organiser regions as prognostic factors in breast cancer.

Nucleolar organiser regions (NORs) were stained in paraffin-embedded biopsy specimens of 80 female breast carcinomas by the silver (Ag) technique. The patients were prospectively followed up for a mean of 12.4 years (range 11.5-13.3). The number of different types of Ag-NORs was correlated with the histological grade, clinical stage, DNA ploidy, S-phase fraction (SPF) and clinical outcome. Grade III tumours showed higher Ag-NOR counts than low grade tumours. The total number of Ag-NORs (P = 0.0059) and the number of dispersed Ag-NOR (P = 0.0199) were significantly related to DNA ploidy aneuploid tumours showing higher Ag-NOR counts. The number of aggregated Ag-NORs was predictive (P = 0.0413) for the development of metastatic disease during follow-up. On the other hand, crude, cancer-related or recurrence-free survival could not be predicted significantly by the Ag-NORs. The results suggest that the number of Ag-NORs is clearly related to the proliferative activity in breast cancer, but the prognostic value of Ag-NOR counting is inferior to the previously recognised prognostic factors.

Breast Neoplasms↗
PubMed1991

Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction.

Clinical and histological prognostic factors were evaluated by means of Cox's analysis in 265 bladder cancer patients with a mean followup of 10 years. The parameters studied were obtained from the primary biopsies, which included clinical stage, World Health Organization grade, papillary status, morphometrically measured mean nuclear area, standard deviation of nuclear area, mean nuclear area of the 10 largest nuclei, mitotic activity index and volume corrected mitotic index. In univariate survival analysis all of the parameters predicted survival (p less than 0.001). In Cox's analysis the clinical stage was the most important prognosticator (p less than 0.001) followed by papillary status (p less than 0.001), volume corrected mitotic index (p = 0.011) and nuclear area of the 10 largest nuclei (p = 0.091). In stages Ta to T2, grades 1 to 2 tumors the papillary status (p = 0.001), mitotic activity index (p = 0.021) and T category (p = 0.029) showed independent prognostic value. Among the stages Ta to T1 tumors the papillary status included all of the available prognostic information (p = 0.001). In a separate analysis of histological features in all papillary tumors histological grade (p less than 0.001) and mitotic activity index (p = 0.021) were related independently to survival in Cox's analysis. In papillary stages Ta to T2, grades 1 to 2 tumors (mitotic activity index, p = 0.029) and in papillary stages Ta to T1 tumors (volume corrected mitotic index, p = 0.054) mitotic indexes showed independent prognostic value. In grade 2 tumors the papillary status p = 0.004) and mitotic activity index (p = 0.090) had independent prognostic value. The mitotic indexes predicted progression among stages Ta to T1 tumors (p less than 0.001) and within World Health Organization grades significantly. The combination of prognostic parameters into prognostic scores gave a more accurate estimate of survival than the single parameter approach. The results suggest morphometric grading of bladder tumors. However, papillary and nonpapillary tumors require different grade limits.

Aged↗
PubMed1991

Immunohistochemical staining of CA 50 antigen in human bladder cancer. Relation to histologic grade, clinical stage, and prognosis.

The immunohistochemical detection of tumor marker CA 50 was studied in bladder cancer of WHO grades I-III. The material consisted of tumors in 83 patients and the mean clinical follow-up time was thirteen years (range 9.6-22 years). The fraction of CA 50-positive cells (FPtot) in microscopic image was scored 0-100 percent. Also the maximally staining region was selected, and the fraction of CA 50-positive cells in this region was scored 0-100 percent (FPmax). The average staining intensity of CA 50-positive cells was scored from 0 to 3 in the whole section (ASItot) and in the maximally staining area (ASImax). The inverse relation between histologic grade, FPtot (p = 0.0001), and ASItot (p = 0.006) was statistically significant. FPtot (p = 0.039) and ASItot (p = 0.018) were also inversely related to clinical stage. Occurrence of metastasis during the follow-up was associated with low CA 50 positivity (FPtot, p = 0.003; ASItot, p = 0.002). The lower the staining intensity or the lower the fraction of CA 50-positive cells, the more aggressive was the tumor. In survival analysis, low FPtot (p = 0.002) and ASItot (p = 0.007) values were related to high risk of bladder cancer death. The results show that immunohistochemical staining of bladder tumor specimens with CA 50 can be used to predict bladder cancer aggressiveness and survival.

Aged↗
PubMed1991

Nucleolar organiser regions (AgNORs) as predictors in transitional cell bladder cancer.

The predictive value of silver stained nucleolar organiser regions (AgNORs) was assessed in 229 patients with transitional cell bladder cancer followed up for over 10 years. The AgNORs were enumerated in pretreatment biopsy specimens. The AgNORs were related to clinical stage (T) (P = 0.0111), papillarity (P less than 0.0001), WHO grade (P less than 0.0001), DNA ploidy (P = 0.0010) and S-phase fraction (P less than 0.0001). Tumours presenting with pelvic lymph node involvement (P = 0.0085) or metastasis (P = 0.0780) at the time of diagnosis had more AgNORs than tumours confined to the bladder wall. Progression in T-, N- and M-categories (P = 0.0010-0.0030) was related to AgNORs and consequently they predicted bladder cancer related survival (P = 0.0005). The diploid tumours could be regrouped according to survival by AgNORs (P = 0.0001). In papillary tumours AgNORs predicted progression (P = 0.0110) and survival (P = 0.0038). In Ta-T1 tumours AgNORs predicted progression (P = 0.11) and survival (P = 0.0751) and also in T2-T3 tumours AgNORs contributed to survival significantly (P = 0.0039). The AgNORs subdivided WHO grade III tumours according to their ability to progress during the follow-up time (P = 0.0711). In a multivariate analysis AgNORs predicted progression independently in Ta-T1 category (P = 0.0165). AgNORs predicted recurrence free period like SPF (P = 0.0010). In conclusion, AgNORs are inferior to classic prognostic factors or DNA flow cytometric variables in muscle invasive bladder cancers whereas they have independent predictive value in superficial cancers.

Carcinoma, Transitional Cell↗
PubMed1991

Intratumoral heterogeneity of DNA indexes in transitional cell bladder cancer: relation to tumor histology.

DNA flow cytometry (FCM) was performed from multiple samples in 60 transitional cell bladder carcinomas (TCC) to detect intratumoral heterogeneity of DNA index (DI). The samples for analysis were selected randomly and they were paraffin-embedded peroperative biopsy specimens from the primary TCCs. Intratumoral heterogeneity of DI was found in 12 of 60 (20%) samples. All WHO grade I tumors were diploid whereas 12 of 41 (29%) WHO grade II-III tumors showed a heterogeneous DI. DI heterogeneity was related to WHO grade (p = 0.004), mitotic frequency (p = 0.002), inflammatory cell infiltration (ICI; p = 0.003) and nonpapillar growth pattern (p = 0.06). In multivariate analysis, the WHO grade (p = 0.027) and the degree of ICI (p = 0.041) were independently related to heterogeneous DI. The results show that (a) many of the WHO grade II-III TCCs are composed of diploid and aneuploid cell populations; (b) the presence of dense ICI and TCCs may lead to false diploid DI. Consequently, the analysis of multiple samples is recommended in WHO grade II-III tumors to detect aneuploidy particularly when dense ICIs are present.

Aneuploidy↗
PubMed1991

Relationship between DNA flow cytometric data, nuclear morphometric variables and volume-corrected mitotic index in transitional cell bladder tumors.

The relationship between the mean nuclear area, standard deviation of the nuclear area, the mean area of the 10 largest nuclei in a section (NA10), volume-corrected mitotic index (M/V index), DNA index (DI) and S-phase fraction (SPF) were assessed in a panel of 222 transitional cell bladder tumors. The relations between the morphometric variables and DI (p less than 0.0001), and between the morphometric variables and SPF (p less than 0.0001) were highly significant. Pearson's correlation coefficients between NA10 and DI (r = 0.413) and between SPF and the M/V index (r = 0.536) were also highly significant (p less than 0.0001). The SPF could be estimated reliably by morphometric methods, whereas the estimation of DI is not perfect. The combination of morphometric variables allowed a more reliable estimation of flow cytometric parameters. The results suggest that DI and SPF can be semiquantitatively estimated in routine histopathological sections by simple morphometric methods.

Carcinoma, Transitional Cell↗
PubMed1991

Prediction of T1-2 GI-II transitional cell bladder cancer; evaluation by histoquantitative methods.

A retrospective clinicopathological study was done including 175 T1-2 GI-II bladder cancer patients who all had transurethral resection or electrocoagulation as their initial treatment. Using interactive morphometry mean nuclear area (NA), mean standard deviation of nuclear area (SDNA) and the mean area of the 10 largest nuclei (NA10) were measured in the biopsies from primary tumours. The volume corrected mitotic index (M/V index) was estimated in the same sections. The histological grading was done according to WHO and clinical staging according to UICC. Progression in bladder cancer was observed in 36 cases. The progression (T-category) was related to M/V index (p = 0.0039), non-papillar growth (p = 0.0249), histological grade (p = 0.0736) and SDNA (p = 0.1535) in that order. In a separate analysis of papillary tumours NA10 showed predictive value (p = 0.0805) in addition to M/V index (p = 0.0067). Twenty-one patients died of bladder cancer and NA (p = 0.0069) as well as M/V index (p = 0.0984) predicted survival whereas other parameters had no substantial prognostic value. In a separate analysis of papillary tumours NA (p = 0.0209) and M/V index (p = 0.0402) predicted survival. The recurrence rate or recurrence-free period could not be significantly related to histological parameters. The results suggest the use of these morphometric features in place for histological grading in prediction of T1-T2 bladder tumours. In addition the results suggest the use of more aggressive therapy and more intensive follow-up programs for rapidly proliferating tumours as expressed by high mitotic activity.

Aged↗
PubMed1990

Prediction of superficial bladder cancer by histoquantitative methods.

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.

Aged↗
PubMed1990

Comparison of morphometry and DNA flow cytometry with standard prognostic factors in bladder cancer.

In 83 bladder cancer patients with adequate follow-up (mean 13 years, range 9-22) the prognostic value of morphometric, DNA flow cytometric and clinical parameters was assessed. Paraffin embedded material was used in flow cytometry. Univariate life-table analysis showed the statistically significant relation of clinical stage, histological grade, mean nuclear area, the Standard Deviation (SD) of nuclear area, mean maximal nuclear diameter, mean nuclear perimeter and the volume corrected mitotic index (M/V index) to survival when bladder cancer deaths alone were used in the analysis. The recurrence of bladder cancer could be predicted with the M/V index. Survival analysis with Cox's regression model pointed to primary tumour clinical stage as the most important prognostic factor of crude survival. Histologically, grade and the SD of nuclear area were the best prognostic factors. Primary tumour stage and histological grade were the best predictors of death from bladder cancer. In Cox's model, histoquantitative methods are almost as good as clinical staging in predicting prognosis. DNA flow cytometry of paraffin embedded material offered no advantage over clinical stage, histological grade or morphology in assessing prognosis.

Adult↗
PubMed1990

DNA ploidy and S phase fraction in human bladder cancer. Relation to survival and histological grade (WHO).

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.

Aged↗
PubMed1990

Prognostication of bladder carcinoma by immunohistochemistry: refined and combined analysis of staining for MCA and CA50.

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)

Aged↗
PubMed1990

Volume-corrected mitotic index and mitotic activity index in transitional cell bladder cancer.

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.

Aged↗
PubMed1990

Potential of nuclear morphometry and volume-corrected mitotic index in grading transitional cell carcinoma of the urinary bladder.

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.

Carcinoma, Transitional Cell↗
PubMed1990

Volume-corrected mitotic index in human pancreatic cancer. Relation to histologic grade, clinical stage, and prognosis.

A retrospective study was performed on 59 pancreatic cancer patients diagnosed during 1970-1988. The mean follow-up time of all individual patients was 6.9 months (range, 0-37 months). Histologic grade, clinical stage (UICC), and volume-corrected mitotic index (M/V index) were correlated to the survival of patients. Histologic grade (p = 0.167) and clinical stage (p = 0.066) were not related to overall survival with statistical significance. The M/V index was significantly associated with overall survival (p = 0.004). M/V index (p = 0.004), clinical stage (p = 0.029), and histologic grade (p = 0.126) predicted survival at 1 year after diagnosis. M/V index divided grade-II tumors into two prognostically different groups (p = 0.050). Seven of 59 patients who survived more than 12 months had an M/V index less than 2, and patients who survived less than 6 months had significantly higher M/V index values (chi-square = 528.3, p less than 0.001). The metastasizing potential of pancreatic cancer and lymph node involvement was also associated with the M/V index. Histologic grade and M/V index were positively correlated (chi-square = 38.6, p less than 0.001, r = 0.702). On the basis of our results, it seems that the M/V index is better than histologic grade or clinical stage in predicting survival of pancreatic cancer patients. This result suggests the potential use of the M/V index in selecting patients for different modes of therapy.

Adenocarcinoma↗
PubMed1990

Volume corrected mitotic index (M/V index) in human bladder cancer; relation to histological grade (WHO), clinical stage (UICC) and prognosis.

A retrospective study was performed on 83 bladder cancer patients diagnosed at the Department of Surgery, Kuopio University Central Hospital, during the years 1965-1987. The follow-up time was 22 years, and the mean follow-up time of individual patients was 13 years (range 9.4-22 years). Histological grade (WHO), volume corrected mitotic index (M/V index) and clinical stage (UICC) were correlated to the survival of patients. Histological grade, M/V index and clinical stage were associated with crude survival (all causes of death included) with little predictive power. The recurrence of the disease could be predicted by the M/V index, but not by histological grade or clinical stage. When bladder cancer deaths only were included, histological grade (chi 2 = 26.6, p less than 0.001), M/V index (chi 2 = 6.6, p = 0.042) and clinical stage (chi 2 = 31.7, p less than 0.001) were clearly associated with prognosis. Also the metastasizing potential of bladder carcinomas could be predicted by the M/V index and by the histological grade at the time of primary diagnosis. Histological grade and M/V index were positively correlated (chi 2 = 16.7, p = 0.002, r = 0.47). In multivariate analysis clinical stage, histological grade and M/V index predicted prognosis in the order of importance.

Aged↗