Biomedical subjects

P K Lipponen

Publications and source records attributed to P K Lipponen.

64 records · Page 4Linked to original sources

PubMed1990

Morphometry in human transitional cell bladder cancer. Nuclear area and standard deviation of nuclear area--relation to tumor grade (WHO) and prognosis.

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.

Aged↗

PubMedDate not supplied

Inducible nitric oxide synthase (iNOS) expression and its prognostic value in prostate cancer.

OBJECTIVES: The expression of inducible nitric oxide synthase (iNOS) was evaluated in prostate cancer and the results were compared with other prognostic factors and patients outcome. MATERIALS AND METHODS: Clinical and histopathological data and follow-up information of 198 prostate cancer (PC) patients treated between the years 1973 and 1992 at Kuopio University Hospital, Finland were collected from patient files. Archival tumor specimens were used for immunohistochemical analysis of iNOS. The expression of iNOS was analysed by light microscopy and the expression was scored into 3 grades (negative weak or strong). RESULTS: iNOS was expressed in tumor cells and in inflammatory cells inside and around the tumor. Normal and hyperplastic prostate tissues adjacent to tumors were negative or weakly positive for iNOS. The strong iNOS expression in tumor cells was related to high T-classification (p=0.001), metastasis (p=0.06), high Gleason score (p=0.0004), DNA aneuploidy (p=0.0001) and perineural infiltration (p=0.0001). iNOS expression was not linked with the density of tumor infiltrating lymphocytes or the expression of p53. The mean values of Ki-67, mitotic index and S-phase fraction were higher in tumors strongly expressing iNOS. In univariate survival analysis the strong expression of iNOS was a significant predictor of poor survival in the entire cohort (p=0.0002) and in the MO patients (p=0.008), but was not an independent predictor of survival in Cox's multivariate analysis. CONCLUSION: iNOS has been related to stimulative and suppressive effects on cancer cell growth, but the prognostic value of iNOS has not been previously studied in PC. Here we could demonstrate an association between strong iNOS expression and rapid cancer cell proliferation rate, dedifferentiation and advanced stage cancer. The strong iNOS expression was a predictor of poor survival in univariate analysis, but was inferior to established prognostic factors in multivariate analysis.

Adenocarcinoma↗

PubMedDate not supplied

Cell proliferation of transitional cell bladder cancer determined by PCNA/cyclin immunostaining. A histopathological description.

The fraction of proliferating cells in 178 transitional cell carcinomas (TCCs) was determined by proliferating cell nuclear antigen (PCNA/cyclin) immunostaining. The fraction of positive nuclei ranged between 0% and 100%. In WHO grade 1 tumours only occasional cells were positive for PCNA/cyclin, whereas nearly all of the nuclei in WHO grade 3 tumours were positive for PCNA/cyclin (p less than 0.0001). Nodular tumours showed a higher growth fraction than papillary tumours (p less than 0.0001). Superficial Ta-T1 tumours showed a significantly lower fraction on nuclei positive for PCNA/cyclin than muscle invasive tumours (p less than 0.0001). Tumours with pelvic lymph node metastasis also had a high growth fraction (p less than 0.0001). The growth fraction as determined by PCNA/cyclin immunostaining was significantly related to aneuploidy (p less than 0.0001, S phase fraction (p less than 0.0001) and mitotic frequency (p less than 0.0001). The results show that cell proliferation in the context of histopathology can be assessed by PCNA/cyclin immunostaining in TCC. The results suggest that PCNA/cyclin immunostaining has prognostic value in TCC and consequently is clearly a subject for further studies as a prognostic variable.

Antigens, Neoplasm↗

PubMedDate not supplied

Histological and quantitative prognostic factors in transitional cell bladder cancer treated by cystectomy.

A cohort of 103 transitional cell bladder tumours (TCC) treated by cystectomy was followed up over 9 years. Patients treated with radiation and cystectomy had a more unfavorable prognosis than patients treated by cystectomy alone (p < 0.0001). Old patients had an unfavorable prognosis after cystectomy, whereas none of the patients under the age of 50 died of TCC after cystectomy (p = 0.027). WHO grade (p = 0.002), high mitotic rate (p = 0.012) and nodular growth pattern (p = 0.004) were signs of ominous disease outcome in univariate survival analysis. Dense inflammatory cell infiltrates in the tumour itself or around invasive tumour cells were signs of good prognosis after cystectomy (p = 0.001) in a multivariate analysis. Clinical stage or nuclear morphometric factors had no independent prognostic value after cystectomy. The results clearly show that the intrinsic malignancy of TCC and host defence mechanisms together determine the prognosis after cystectomy. The evaluation of malignant features in TCC alone is an insufficient means of predicting prognosis in invasive TCC and the analysis of host immune response should be included in the prognostic evaluation.

Age Factors↗

PubMedDate not supplied

Volume corrected mitotic index (M/V index), mitotic activity index (MAI), and histological grading in breast cancer.

A prospective study on breast cancer was started in 1975, and ended in 1987 allowing a mean follow-up of 12.4 years. At the operation tumor size was registered, and after axillary evacuation axillary status was defined histologically. In 1989-1990 volume corrected mitotic index (M/V index), and mitotic activity index (MAI) were estimated, and histological grading performed from archival paraffin sections. In univariate survival analysis axillary node status (p less than 0.0001), M/V index (p less than 0.0001), MAI (p = 0.0001), and tumor size (p = 0.0009), histological grade (p = 0.0195), and irregularity of nuclei (p = 0.0167) predicted survival, recurrence free survival, and breast cancer survival. In a multivariate survival analysis axillary node status, M/V index, tumor size and tubular growth pattern showed independent prognostic value in the order of significance. In the separate analysis of infiltrative ductal or lobular carcinomas the M/V index was the most important prognosticator. The results suggest that the M/V index is more powerful in predicting survival than the mitotic activity index (MAI) in breast cancer. Obviously this is due to better control of variation factors associated with field size and area of epithelium by the M/V index.

Axilla↗

PubMedDate not supplied

Nucleolar organiser regions (NORs) in bladder cancer; relation to histological grade, clinical stage and prognosis.

Nucleolar organiser regions (NORs), which are related to regulation of protein synthesis and cell proliferation, were estimated subjectively in 89 bladder cancer patients by means of silver staining technique on archival paraffin sections. The number of Ag-NORs was correlated to histological grade (WHO), clinical stage (UICC) and clinical behaviour of tumours during a mean follow-up period of 14 years. Total number of Ag-NORs and the number of dispersed Ag-NORs were significantly related to histological grading and clinical stage. In particular, grade III tumours (p = 0.0002) as well as T3-T4 tumours (p = 0.0591) showed high numbers of Ag-NORs in comparison to superficial low grade tumours. Non-papillary tumours showed higher Ag-NOR counts as cell (p = 0.0012). Ag-NOR count was also related to lymph node involvement (p = 0.0418) and metastasis (p = 0.0713) with borderline significance. Patients dying of bladder cancer showed higher Ag-NOR counts and in survival analysis the number of dispersed Ag-NORs was related significantly to survival (p = 0.0201). Our conclusion is that despite significant differences in Ag-NOR counts they are of limited use for diagnosis and prediction of any single case in bladder cancer. The results, however, clearly indicate the need for further studies before the clinical importance of the Ag-NOR staining method can be fully appreciated in bladder cancer.

Female↗

PubMedDate not supplied

How to count mitoses in bladder cancer grading?

The prognostic value of volume corrected mitotic index (M/V index) was improved in bladder cancer by correcting the M/V index for mean nuclear area (NA) in a section as an estimate of cellularity. The clinical follow-up data of 265 patients were obtained from patient files. The M/V index was counted in the biopsy specimens from the primary tumours and the NA was measured by means of IBAS 1&2 image analyser. The analysis showed that both M/V index and nuclear area corrected M/V index (MAM/V index) were related significantly to histological grade, clinical stage, papillary and progression in T-, N-, and M-categories (p less than 0.0001). In survival analysis NAM/V index was a better prognosticator (X2 = 25.5, p less than 0.0001) than M/V index (X2 = 14.4, p = 0.0007), due to better prediction of large celled high grade tumours. Recurrence-free period (RFP) was related significantly to NAM(V index (p = 0.0006) and to M/V index (p less than 0.0823)0 in that order. In conclusion, the correction of M/V index for NA as an estimate of cellularity in a section does not improve the prognostic value of M/V index in superficial bladder tumours, but it gives better grading results than the original M/V index in advanced tumours.

Cell Nucleus↗

PubMedDate not supplied

Classic prognostic factors, flow cytometric data, nuclear morphometric variables and mitotic indexes as predictors in transitional cell bladder cancer.

One hundred and eighty-seven patients with a transitional cell bladder cancer were followed by retrospectively for a mean of 9.5 years. Clinical stage (p less than 0.0001), histological grade (p less than 0.0001), papillary (p less than 0.0001), SPF (p less than 0.0001), M/V index (p less than 0.0001), MAI (p less than 0.0001), DNA index (p = 0.0001) SDNA (p = 0.0004), NA10 (p = 0.0023), NA (p = 0.0044) and G2% (p = 0.0158) were significantly correlated with survival in univariate analysis. In Cox's analysis T-category, papillarity and MAI had independent prognostic value and in combination they predicted bladder cancer-related survival significantly (X2 = 117.5, p less than 0.0001). When histological parameters only were analysed, WHO grade, SPF and papillarity were independent predictors and their combined prognostic significance was high (X2 = 76.6, p less than 0.0001). In papillary tumours SPF (p v 0.0005), MAI (p = 0.0009), DNA index (p = 0.0010) and M/V index (p = 0.0021) predicted survival significantly in addition to stage (P less than 0.0001) and grade (p = 0.0003) in univariate analysis. In Cox's analysis T-category, MAI and M/V index were independent predictors and their combined prognostic value was high (X2 = 54.1, p less than 0.0001). In Ta-T1 and in T2-T3 tumours, WHO grade, papillarity, SPF, mitotic indexes and DI were significant predictors in univariate analysis. In Cox's analysis of Ta-T1 tumours papillarity had independent prognostic value, whereas in papillary Ta-T1 tumours mitotic activity included all prognostic information. In T2-T3 tumours WHO grade and SPF were independent predictors. In conclusion, in papillary bladder tumours T-category is the most important predictor of survival followed by parameters reflecting proliferative activity of cancer cells.

Aged↗

PubMedDate not supplied

Stereologically measured nuclear volume in comparison to two-dimensional nuclear morphometry, mitotic index and flow cytometry in predicting disease outcome in bladder cancer.

The prognostic value of stereologically estimated nuclear volume was compared to the prognostic value of clinical, histological, morphometric and flow cytometric prognostic factors in a cohort of 212 patients followed up for over 11 years. T-category (p = 0.014), grade (p < 0.0001), papillary status (p = 0.001), nuclear area (p < 0.0001), SD of nuclear area (p < 0.0001), DNA ploidy (p < 0.0001), S phase fraction (p < 0.0001), mitotic index (p < 0.0001) and nuclear volume were significantly interrelated. Progression in T- (p = 0.090), N- (p = 0.007) and M-categories (p = 0.001) was related to nuclear volume, while independent predictors of progression in a multivariate analysis were grade and S phase fraction. Nuclear volume predicted survival in the entire cohort (p = 0.0004) and in papillary tumours (p = 0.0048), whereas in superficial tumours it had no prognostic value. In multivariate survival analysis T-category (p < 0.001), papillary status (p < 0.001) and S phase fraction (p = 0.011) predicted survival and S phase fraction predicted (p = 0.052) recurrence-free survival in Ta-T1 tumours. The results suggest that stereological measurement of nuclear volume provides no additional prognostic information over proliferation indices (mitotic index, S phase fraction) in bladder cancer.

Aged↗

PubMedDate not supplied

Expression of insulin-like growth factor II in female breast cancer as related to established prognostic factors and long-term prognosis.

The expression of insulin-like growth factor II (IGF-II) was analysed immunohistochemically in a series of 211 breast cancers with special reference to standard prognostic factors and patient survival. IGF-II was expressed both in the cancer cells and in stromal cells, in 84% and 50% of cases, respectively. IGF-II expression in cancer cells was related to a non-metastatic disease at diagnosis (p = 0.03), low tumour grade (p = 0.02), DNA diploidy (p = 0.02) and S-phase fraction under 7% (p = 0.001). IGF-II negativity was positively correlated to morphometric SD of nuclear area (p = 0.0003), nuclear perimetry (p = 0.002), SD of nuclear perimetry (p = 0.02), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.003). The expression of IGF-II in stromal cells was related to low histological grade (p = 0.02), mitotic index under 10/mm2 (p = 0.01), mild nuclear pleomorphism (p = 0.03), DNA diploidy (p = 0.08), SD of nuclear area (p = 0.006), mean nuclear perimeter (p = 0.05), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.007) in that the nuclear factor values were higher in tumours without stromal IGF-II expression. In univariate and multivariate survival analysis, immunohisto-chemically detected expression of IGF-II had no independent prognostic value over standard prognostic factors. Despite the fact that expression of IGF-II was inversely related to several histopathological features of malignancy, the clinical behaviour of breast cancer seemed to be independent of IGF-II expression.

Adult↗