Biomedical subjects

P K Lipponen

Publications and source records attributed to P K Lipponen.

At least 37 records · Page 2Linked to original sources

PubMed1994

Proliferating cell nuclear antigen and p53 expression as prognostic factors in T1-2M0 prostatic adenocarcinoma.

The expression of proliferating cell nuclear antigen and p53 protein was analysed by immunocytochemical methods (PC10, CM1 antisera) in 139 patients with T1-2M0 prostatic adenocarcinomas followed-up for > 12 years. p53 protein was expressed in 21 (15%) tumours (15%), the fraction of positive nuclei being very low (mean SE, 1% +/- 0.7%). Accumulation of p53 protein in epithelial cells was independent of tumour stage and Gleason score, and had no effect on prognosis. In 4 cases, p53 protein was expressed only in stromal cells. The fraction of PCNA-positive nuclei (evaluable in 116 cases) was higher in T2 than in T1 tumours (p < 0.001); furthermore, high Gleason score was positively correlated with PCNA positivity (p < 0.001). A finding of over 5% of PCNA-positive nuclei predicted progression in T and M categories and were a sign of poor outcome. The fraction of PCNA-positive stromal-cell nuclei was related to T-category with a borderline significance (p = 0.06). In a multivariate analysis of the prognostic factors, independent predictors of survival included Gleason score (p < 0.001), fraction of PCNA-positive nuclei (p = 0.013), observation before therapy (p = 0.05), and T-category (p = 0.07) in that order of significance. The results suggest that overexpression of p53 protein is of marginal prognostic value in local prostatic adenocarcinomas, whereas direct measurement of cell proliferation by PCNA immunolabelling provides important prognostic information in T1-2M0 tumours, in addition to the Gleason score.

Adenocarcinoma↗

PubMed1994

Expression of pS2 protein in transitional cell bladder tumours.

A series of 201 bladder cancer biopsy specimens was analysed immunohistochemically for the expression of pS2 protein. Altogether, 61 per cent of the tumours were pS2-negative; in 16 per cent less than 1 per cent and in 23 per cent of cases more than 1 per cent of cells were pS2-positive. Normal transitional epithelium was negative for pS2. The fraction of positive cells was higher in poorly differentiated non-papillary tumours and in invasive tumours with pelvic lymph-node (P = 0.05) and distant metastasis (P = 0.10). pS2 expression was not related to sex, while patients aged 60-70 years had low fractions of pS2-positive cells (P = 0.03). DNA ploidy, S-phase fraction, mitotic index, morphometric nuclear features, and expression of c-erbB-2, p53, and epidermal growth factor receptor were independent of expression of pS2. Tumours expressing pS2 in over 10 per cent of cells had a lower survival probability (P = 0.0486). The results show that pS2 is expressed in 40 per cent of transitional cell bladder tumours, but that this marker has no clinical significance over established prognostic factors.

Adult↗

PubMed1994

Apoptosis in bladder cancer as related to standard prognostic factors and prognosis.

Four hundred cases of transitional cell bladder cancer were reviewed by light microscopy for the presence of apoptotic cells in the primary tumour biopsy specimens. The number of apoptotic cells/mm2 of neoplastic epithelium (apoptotic index, AI) was related to various histological features and prognosis. AI was related significantly to high T-category, high grade, DNA aneuploidy, large nuclear morphometric variable values, and high proliferation rate of cancer cells. Tumours showing overexpression of p53 oncoprotein in over 10 per cent of the nuclei had significantly higher AI values than p53-negative tumours. Multivariate regression analysis showed that AI was independently predicted by mitotic index, mean nuclear area, and papillary status. Progression, recurrence-free survival, and survival of superficial tumours were all related significantly to AI. In multivariate survival analysis, T-category, papillary status, grade, and mitotic index had independent prognostic value, while the recurrence-free survival of Ta-T1 tumours was related independently to AI. The results show that AI is related particularly to mitotic activity in transitional cell bladder tumours, while AI as assessed by light microscopy hardly has any independent prognostic significance.

Adult↗

PubMed1993

Over-expression of p53 nuclear oncoprotein in transitional-cell bladder cancer and its prognostic value.

Two hundred and twelve archival bladder-cancer biopsy specimens were analyzed immunohistochemically analysis were correlated to established histological and quantitative prognostic factors and survival of patients during a mean follow-up period of more than 10 years. Twenty-nine percent of tumours were positive for p53 protein, and over-expression was associated with high histological grade, non-papillary growth architecture, dense inflammatory cell reaction, DNA aneuploidy, high S-phase fraction, high mitotic frequency and high SD of nuclear area. Progression in T, N and M categories was significantly related to over-expression of p53 protein. In univariate survival analysis, over-expression of p53 predicted poor outcome in the entire cohort, in papillary tumours and in muscle-invasive tumours but not in superficial tumours. In a multivariate survival analysis, over-expression of p53 oncoprotein had no independent prognostic value over clinical stage and mitotic index. The results confirm that p53 is involved in the growth regulation of bladder cancer and is certainly a subject for detailed analysis of specific mutations.

Carcinoma, Transitional Cell↗

PubMed1993

Flow cytometry in comparison with mitotic index in predicting disease outcome in transitional-cell bladder cancer.

The DNA content and S-phase fraction were measured by flow cytometry in 448 tumour biopsy specimens from transitional-cell bladder cancer (TCC). The samples were also analyzed for mitotic index, WHO grade and papillary status, and histological and flow cytometric data were then correlated to clinical behaviour of tumours during a mean follow-up period of 9.9 years. TNM classification, WHO grade, papillary status, mitotic index, DNA ploidy and S phase fraction were significantly interrelated. Twenty-four percent of tumours showed heterogeneous DNA indices when measured from multiple samples (measured in 94 cases). Of the histological parameters, independent predictors of progression in superficial tumours were the S-phase fraction and mitotic index. In superficial tumours, S-phase fraction and the mitotic index included all the available independent prognostic information in survival analysis, whereas in muscle-invasive tumours T category was the most important prognostic factor. The results suggest that DNA ploidy has no independent prognostic value in transitional-cell bladder cancer, whereas proliferation indices (SPF, mitotic index) are important prognostic factors. Accordingly, malignancy classification of papillary bladder tumours can be based on proliferation indices alone. Nodular tumours run an unfavourable course and their malignancy grading by flow cytometry or by mitotic index is not relevant.

Aged↗

PubMed1993

The prognostic value of basement membrane morphology, tumour histology and morphometry in superficial bladder cancer.

This analysis evaluated the prognostic importance of clinical, histological (WHO grade, papillary status, tumour-infiltrating lymphocytes) and morphometric factors (mitotic index, mean nuclear area, SD of nuclear area) in a cohort of 132 patients with a Ta-T1 transitional cell bladder cancer followed-up for over 8 years. Special attention was given on the state of the subepithelial basement membrane (BM) and subepithelial vascular density as demonstrated by type IV collagen immunostaining. Defects in the BM and dense vascular network were related to nodular growth pattern, high histological grade, rapid cancer cell proliferation and a dense inflammatory cell infiltrate (tumour-infiltrating lymphocytes, TIL) in tumour stroma. The most important predictor of progression was the mitotic index (P < 0.0001) followed by vascular density (P = 0.0054), the state of the BM (P = 0.0056), density of TIL (P = 0.0193), WHO grade (P = 0.0356) and papillary status (P = 0.0448). In univariate survival analysis the mitotic index (P < 0.0001), the state of the BM (P < 0.0001), subepithelial vascular density (P = 0.0013) and WHO grade (P = 0.01) predicted survival. In a multivariate analysis the mitotic index (P < 0.0001) and the state of the BM (P = 0.008) were independent predictors. The results show that the evaluation of the mitotic rate and investigation of the continuity of the BM should be done whenever the prognosis of Ta-T1 tumours of the bladder is assessed.

Aged↗

PubMed1993

Grading of superficial bladder cancer by quantitative mitotic frequency analysis.

A cohort of 270 superficial (stages Ta to T1) transitional cell bladder tumors was followed for more than 8 years. World Health Organization (WHO) grade, papillary status and 2 mitotic indexes were related to progression, recurrence-free survival and bladder cancer related survival during followup. Mitotic activity index and volume corrected mitotic index were significantly related to WHO grade and papillary status (p < 0.0001). WHO grade, papillary status and mitotic indexes were related significantly to progression in univariate analysis (p < 0.001) whereas in a multivariate analysis only volume corrected mitotic index included independent prognostic information (p < 0.001). Recurrence-free survival was related to volume corrected mitotic index in the entire cohort (p = 0.03) and in papillary tumors (p = 0.07). Bladder cancer related survival was related to WHO grade, papillary status, mitotic activity index and volume corrected mitotic index (all p < 0.0001). In papillary tumors mitotic activity index (p < 0.0001), volume corrected mitotic index (p < 0.0001) and WHO grade (p = 0.0036) predicted survival. In multivariate analysis mitotic activity index predicted independently recurrence-free survival in the entire cohort (p = 0.043) and in papillary tumors (p = 0.012). Bladder cancer survival in the entire cohort and in papillary tumors was related independently to volume corrected mitotic index (p < 0.001). The results show that superficial transitional cell bladder tumors can be efficiently categorized into prognostic groups by quantitative mitotic frequency analysis and the results provide a new classification system for superficial transitional cell bladder tumors.

Aged↗

PubMed1993

Expression of C-50 antigen as a prognostic variable in transitional cell bladder tumours.

The immunohistochemical expression of C-50 antigen was quantitated in paraffin-embedded biopsy specimens of 218 transitional cell bladder tumours. The patients were treated according to standard practice in one institution and followed up for over 10 years. The expression of C-50 antigen was inversely correlated to T category, papillary status and WHO grade. Aneuploid tumours with a high S phase fraction (SPF) showed low expression of C-50 antigen. Progression in T, N and M categories was inversely correlated to CA-50 expression. Low expression of C-50 antigen predicted progression in Ta-T1 tumours. Expression of C-50 antigen was related to a favourable prognosis in the whole series, in papillary tumours, in diploid tumours, in WHO grade 2 tumours and in Ta-T1 tumours. The combination of DNA ploidy and expression of C-50 antigen was a highly significant predictor of survival. In Cox's analysis, expression of CA-50 had an independent predictive value in Ta-T1 tumours, whereas in the whole cohort the T category and papillarity were independent predictors.

Aged↗

PubMed1993

Proliferation indices as independent prognostic factors in papillary Ta-T1 transitional cell bladder tumours.

A cohort of 148 patients with papillary Ta-T1 transitional cell carcinomas (TCCs) was followed up for over 10 years and flow cytometric (DNA ploidy, S phase fraction) and morphometric variables (5 nuclear factors, volume corrected mitotic index) were related to prognosis during this period. Recurrence-free survival was significantly related to DNA ploidy, S phase fraction and M/V index. Progression in T-category was predicted by M/V index, S phase fraction, DNA ploidy and WHO grade. The same variables predicted progression in N- and M-categories. In a multivariate analysis only M/V index and S phase fraction were independent predictors of progression. Univariate analysis showed that M/V index, SPF, DNA ploidy and WHO grade predicted survival. In a multivariate survival analysis only M/V index and SPF were independent predictors. The results showed that proliferation indices had independent prognostic value in papillary Ta-T1 TCCs and the grading of these tumours could be based on the proliferation indices. Papillary Ta-T1 tumours with a M/V index value < or = 10/mm2 or SPF < or = 10% had a favourable prognosis whereas tumours with M/V index > 10/mm2 or SPF > 10% had a high malignant potential.

Aged↗

PubMed1993

Interrelationship between expression of p53, proliferating cell nuclear antigen and c-erbB-2 in bladder cancer.

The expression of c-erbB-2, p53 and proliferating cell nuclear antigen (PCNA) was studied using immunocytochemical techniques in paraffin-embedded biopsy specimens (consecutive 5-microns sections) from 104 transitional cell bladder tumours. 46/104 (44%) of the tumours were positive for c-erbB-2, 29/104 (28%) for p53 and 88/104 (85%) for PCNA. The expression of these antigens was independent of T-category, whereas the expression was significantly related to histological differentiation and papillary status so that non-papillary high-grade tumours were usually positive for all the antigens. The expression of c-erbB-2 and p53 was intense in 8/104 (8%) of cases and weak or absent in 76/104 (73%) of cases (p = 0.0003). The expression of p53 and PCNA was intense in 22/104 (21%) and weak or absent in 76/104 (73%) of tumours (p = 0.0003). Intense expression of c-erbB-2 and PCNA was also interrelated significantly (p = 0.0202). All three antigens were simultaneously expressed in 16-29% of T2-T4 tumours, in 22-35% of grade 2-3 tumours and in 35% of non-papillary tumours.

Carcinoma, Transitional Cell↗

PubMed1993

Clinical prognostic factors in transitional cell cancer of the bladder.

A cohort of 537 patients with transitional cell cancer of the bladder (TCC) were followed up for a mean of 9 years and the clinicopathological data were related to prognosis. The T category (p < 0.0001), N category (p < 0.0001) and M category (p < 0.0001) were the most important clinical prognostic factors, followed by the age of the patient (p < 0.0001). Of the histological variables the WHO grade (p < 0.0001), papillary status (p < 0.0001) and the presence of R3-4 cells in voided urine (p = 0.0061) predicted unfavorable prognosis. In Ta-T1 tumors the WHO grade (p < 0.0001), papillary status (p < 0.0001) and the age of the patient (p < 0.0001) had a prognostic value in univariate analysis. In Cox's analysis independent predictors of survival were the T category (p < 0.0001), WHO grade (p < 0.0001), patient age (p < 0.0001), papillary status (p = 0.012) and the presence of symptoms before diagnosis (p = 0.033). In superficial tumors the WHO grade (p < 0.0001) and patient age (p < 0.0001) were independent predictors of survival.

Age Factors↗

PubMed1993

Prognostic factors in nodular transitional cell bladder tumours.

A cohort of 106 nodular transitional cell bladder cancers (TCC) were followed up for a mean of 9 years. Clinical stage, WHO grade, six morphometric nuclear factors and volume corrected mitotic index (M/V index) were correlated to progression and survival during the follow-up period. Nuclear factors were related to WHO grade with a borderline significance (p = 0.01-0.3) whereas the M/V index showed a highly significant relation to WHO grade. Neither nuclear factors nor the M/V index were related significantly to T-, N- or M-categories at the time of diagnosis. Progression in N- and M-categories was related independently to WHO grade whereas progression in T-category could not be predicted significantly by none of the variables included in this analysis. Survival was predicted by T-category (p = 0.0028), N-category (p = 0.0001), M-category (p = 0.0057) and M/V index (p = 0.010). In T1-T2N0M0 tumours survival was predicted by the Dmax (p = 0.015) and by the M/V index (p = 0.039). In multivariate survival analysis T-category (p < 0.001) had independent prognostic value. In T1-T2N0M0 tumours only the M/V index predicted survival independently (p = 0.007). The results show that only the proliferation rate in addition to T-category have prognostic significance in nodular TCC.

Aged↗

PubMed1992

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

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.

Carcinoma, Transitional Cell↗

PubMed1992

Prognostic factors in WHO grade 2 transitional-cell bladder cancer (TCC); a novel two-grade classification system for TCC based on mitotic index.

A retrospective histological analysis has been carried out on 537 cases of transitional-cell bladder carcinoma, followed-up over a period of 9 years. In the first part of the study WHO grade 2 tumours were analysed and a number of independent factors predictive for survival identified. In a multivariate analysis the T category and M/V index (number of mitotic figures/mm2 neoplastic epithelium) were the most important prognostic factors. In a subsequent analysis of the whole series of 537 cases, overall the M/V index was not as important in predicting survival as the stage of the tumour. However, in superficial tumours (Ta-T1) subsequent analysis showed that the M/V index alone could be used to predict survival.

Aged↗

PubMed1992

Prediction of superficial bladder cancer by nuclear image analysis.

A cohort of 270 superficial transitional cell bladder tumours (Ta-T1) was followed-up for over 8 years. WHO grade, papillary status and six nuclear factors were related to progression, recurrence-free survival (RFS) and bladder cancer-related survival (BS) during the follow-up period. Mean nuclear area (NA), standard deviation of nuclear area (SDNA), nuclear perimetry (PE), standard deviation of nuclear perimetry (SDPE), shortest nuclear axis (Dmin) and longest nuclear axis (Dmax) were significantly related to WHO grade and papillary status (P < 0.0001). All the nuclear factors were related significantly to progression in univariate analysis (P < 0.01) whereas in a multivariate analysis WHO grade (P < 0.0001) and papillary status (P = 0.048) included independent prognostic information. RFS was related to PE (P = 0.009), SDPE (P = 0.013), Dmin (P = 0.021), Dmax (P = 0.028) and SDNA (P = 0.029). In papillary tumours SDPE (P = 0.007) and Dmin (P = 0.024) predicted RFS. BS was related to WHO grade, papillary status, NA, SDNA, PE, Dmax, Dmin (all P < 0.0001) and to SDPE (P = 0.003). In papillary tumours PE (P < 0.0001), Dmax (P = 0.0022), Dmin (P = 0.0027), WHO grade (P = 0.0036), NA (P = 0.0005), SDNA (P = 0.0355) and SDPE (P = 0.0718) predicted BS. In multivariate analysis SDPE (P = 0.029) predicted RFS and survival was related to WHO grade (P < 0.001) and PE (P = 0.014) independently. In papillary tumours only Dmax (P = 0.001) predicted survival independently. The results show that superficial papillary transitional cell bladder tumours can be efficiently categorised into prognostic groups by nuclear image analysis and the results provide a new classification system for superficial papillary bladder tumours. Tumours with high nuclear factor values should be considered for radical primary therapy and adjuvant therapy after transurethral resections.

Aged↗

PubMed1992

Tumour infiltrating lymphocytes as an independent prognostic factor in transitional cell bladder cancer.

The prognostic value of tumour infiltrating lymphocytes (TIL) was assessed in a cohort of 514 patients with a transitional cell bladder cancer (TCC) during a follow up period of over 9 years. The density of TIL were positively correlated to WHO grade (P < 0.0001), non-papillary growth architecture (P < 0.0001), morphometric nuclear factors (P < 0.007) and volume corrected mitotic index (M/V index) (P < 0.0001). Dense TIL predicted progression in Ta-T1 tumours (P < 0.0006) whereas in a multivariate analysis they had no independent predictive value. Dense TIL were related to short recurrence-free survival in Ta-T1 tumours in a univariate analysis (P = 0.06) as well as in a multivariate analysis (P = 0.005). Dense TIL predicted unfavourable prognosis in the entire cohort (P = 0.0316) and in papillary tumours (P = 0.062) whereas in nodular tumours TIL were a sign of good prognosis (P = 0.0141). Also in T3-T4 tumours TIL were related to less aggressive behaviour of TCC (P = 0.0259). In a multivariate analysis including clinical stage (T-category), WHO grade, papillary status, six morphometric nuclear factors and M/V index dense TIL were a highly significant indicator of a favourable prognosis (P = 0.007). Particularly TIL categorized rapidly proliferating TCC into prognostic groups (P = 0.001). The results show that TIL are a sign of efficient host defence mechanisms in TCC and TIL predict a favourable prognosis in invasive TCC.

Aged↗

PubMed1992

Independent prognostic factors in T2/T3 transitional cell bladder tumours with special reference to histoquantitative methods.

A cohort of 233 T2/T3 transitional cell carcinomas were followed up for over 10 years. Five nuclear factors, two mitotic indices, DNA ploidy and S-phase fraction (SPF) were related to progression and survival of TCCs during that time period. SPF predicted pelvic lymph node involvement at diagnosis (P = 0.064). Progression in T-category was related to T-category (P = 0.035), DNA ploidy (P = 0.0180), papillary status (P = 0.0021), mitotic activity index (MAI) (P = 0.0011), volume corrected mitotic index (M/V index) (P = 0.0017), WHO grade (P = 0.0003) and S-phase fraction (P = 0.0002). Progression in N and M-categories was related to the same variables. Independent predictors of progression in T-category were SPF (P = 0.0161) and WHO grade (P = 0.0236), whereas progression in M-category was independently related to MAI (P = 0.0012) and T-category (P = 0.0004). The SPF (P < 0.0001), M/V index (P < 0.0001), MAI (P < 0.0001), WHO grade (P < 0.0001) and papillary status (P < 0.0001) were the most important predictors of survival in univariate analysis. In a multivariate analysis SPF and M/V index (P < 0.0001) were the best predictors of survival followed by papillary status and T-category. The results show that the proliferation rate of T2/T3 TCCs as determined by flow cytometric SPF or M/V index are equally powerful predictors. They are clearly better than nuclear morphometry, DNA ploidy or WHO grading as prognostic factors.

Aged↗

PubMed1992

Cell proliferation of transitional cell bladder tumours determined by PCNA/cyclin immunostaining and its prognostic value.

Cell proliferation of transitional cell bladder cancer (TCC) was determined by PCNA (proliferating cell nuclear antigen)/cyclin immunostaining in 178 TCCs and the results were related to established prognostic factors, progression and survival during a mean follow-up period of 10 years. The fraction of PCNA/cyclin positive nuclei was related to T-category (P = 0.008), papillary status, WHO grade, DNA ploidy, S phase fraction, M/V index (volume corrected mitotic index) and AgNORs (silver stained nucleolar organiser regions) (for all P less than 0.001). TCCs presenting with pelvic lymph node metastasis at diagnosis had a significantly higher growth fraction than the tumours confined to the bladder wall (P less than 0.001). The fraction of PCNA/cyclin positive nuclei predicted progression in T-, N- and M-categories (P less than 0.001). In Ta-T1 tumours high fraction of PCNA/cyclin positive nuclei predicted metastasis (P = 0.019). In survival analysis the fraction of PCNA/cyclin positive nuclei predicted survival in the entire cohort (P less than 0.001) and in Ta-T1 tumours (P = 0.0005). In a multivariate survival analysis the fraction of PCNA/cyclin positive nuclei showed independent predictive value in the entire cohort (P = 0.046), in papillary tumours (P = 0.006) and in Ta-T1 tumours (P = 0.015). The results show that the growth fraction as determined by PCNA/cyclin immunostaining is a significant prognostic variable in TCC.

Analysis of Variance↗