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P Lipponen

Publications and source records attributed to P Lipponen.

At least 109 records · Page 6Linked to original sources
PubMed1989

Potential of morphometry in grading transitional cell carcinoma of the urinary bladder.

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.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Prognostic value of cell proliferation in breast cancer as determined by proliferating cell nuclear antigen (PCNA) immunostaining.

A series of 175 biopsies from primary tumours were subjected to immunostaining for proliferation cell nuclear antigen (PCNA) and histopathological analysis for prognostic factors in 175 women with breast cancer followed up for nine years. In normal breast epithelium, only occasional nuclei were positive for PCNA. In breast carcinomas, the fraction of nuclei positive for PCNA showed considerable intratumoural variation, usually being highest at the invasive tumour margins. The fraction of positive nuclei was significantly related to histological grade (p less than 0.001), histological type (p = 0.049) and tumor recurrence (p = 0.01). The fraction of positive nuclei predicted recurrence-free survival (p = 0.007) and overall survival (p = 0.0158) in univariate analysis. In the multivariate analysis including also the standard prognostic factors, the PCNA positivity predicted recurrence-free survival (p = 0.004) and overall survival (p = 0.030) independently. The results show that the light microscopic assessment of the growth fraction as determined by PCNA immunolabeling has independent prognostic value in breast carcinomas like some other (e.g. S phase fraction, mitotic index, Ki-67) previously characterized proliferation indices.

Adult↗
PubMedDate not supplied

Clinical, histological and quantitative prognostic factors in cutaneous malignant melanoma.

A retrospective study including 55 cutaneous melanoma patients with 9.5 years follow-up was carried out to assess the significance of various prognostic factors. The histological samples were evaluated according to Clark's and Breslow's classifications and six nuclear features were measured by interactive morphometry. Mitotic activity was assessed by two different methods: mitotic activity index (MAI) and volume corrected mitotic index (M/V index). The overall disease-related five-year survival of patients was 76.4%. TNM stage (p = 0.0001), sex (p = 0.0024), M/V index (p = 0.003), standard deviation of nuclear form factor (p = 0.023), MAI (p = 0.02), shortest nuclear axis (p = 0.023) and Breslow's classification (p = 0.044) predicted survival in univariate analysis. A multivariate analysis including clinical, histological and morphometric features pointed the Clark's classification as the most important predictor of survival (p = 0.002), while the other variables included had no independent prognostic value. The prognostic importance of mitotic indices and morphometric features is clearly a subject for further studies in superficial melanomas.

Female↗
PubMedDate not supplied

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer.

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment.

Analysis of Variance↗
PubMedDate not supplied

Nucleolar organiser regions (AgNORs) related to histopathological characteristics and survival in prostatic adenocarcinoma.

The number of silver stained nucleolar organiser regions (AgNORs) was assessed in biopsy specimens of 78 patients with prostatic adenocarcinoma followed up for a mean of 15.6 years. The number of Ag-NORs was related to histological features, clinical stage, DNA ploidy, S-phase fraction (SPF) and clinical outcome. In 31/36 (86%) of grade I tumours on average less than 3.5 AgNORs/nucleus were present, whereas of grade III tumours 8/18 (44%) showed usually more than 3.5 Ag-NORs/nucleus (p = 0.0163). The number of Ag-NORs was significantly related to mean nuclear area (NA) (p = 0.017) and to SD of nuclear area (p = 0.05). The Ag-NORs were not related significantly to clinical stage, perineural infiltration, lymphatic infiltration, DNA ploidy, SPF, G2 fraction or M/V index, although there was a clear trend between the variables. In survival analysis, the degree of lymphatic infiltration (LI) (P = 0.009) predicted survival, whereas AgNORs had no significant prognostic value albeit a trend was observed. In T1-T2 tumours, histological grade (p = 0.05), PNI (p = 0.04) and SPF (p = 0.0076) predicted survival.

Adenocarcinoma↗
PubMedDate not supplied

Breast cancer in young women: clinical, histological and morphometric prognostic factors.

Clinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a univariate and in a multivariate survival analysis to assess their independent predictive value in 56 breast cancer patients under the age of 40 years who were followed up for over 10 years. The most important predictor of recurrence-free survival (RFS) in univariate analysis was the SD of nuclear perimetry (p = 0.003) followed by SD of nuclear area (p = 0.006), M/V index (p = 0.036), pN status (p = 0.046), nuclear area of 10 largest nuclei (p = 0.07), nuclear perimetry (p = 0.09) and nuclear area (p = 0.09) in that order. In pN(-) patients, SDPE (p = 0.04), SDNA (p = 0.07) and NA10 (p = 0.07) predicted RFS. In pN+ patients the most important predictor of RFS was the SDNA (p = 0.001) followed by NA 10 (p = 0.003), SDPE (p = 0.009), PE (p = 0.01), NA (p = 0.01) and Dmin (shortest diameter) (p = 0.04). In multivariate analysis the pN-status independently predicted RFS. Tumour size (p = 0.001), pN status (p = 0.002) and M/V-index (p = 0.079) were related to BS (breast cancer survival). In pN-patients, NA 10 (p = 0.097) predicted BS, whereas in pN+ tumours tumour size (p = 0.06) was the most important predictor of BS. In a multivariate analysis, tumour size (p = 0.02) and pN-status (p = 0.016) were independent predictors of BS.

Adult↗
PubMedDate not supplied

Expression of tumour markers CA50, CEA and TPA in female breast carcinoma as related to histopathological findings and survival.

Expression of the tumour markers CEA, TPA and CA 50 was determined immunohistochemically (using a staining index, I) in paraffin embedded biopsy specimens from 114 female breast carcinomas, with special emphasis on tumour histology and patient prognosis. The mean (SD) age of the patients was 58.1 (13.1) years and they were prospectively followed-up for a mean of 12.4 years. The mean (SD) staining index (I) values were as follows: for CEA 0.14 (0.35) (range 0.00-3.00) for TPA 2.01 (0.77) (range 0.00-3.00) and for CA 50 0.36 (0.67) (range 0.00-3.00). Grade I tumours showed higher positivity for TPA than grade III tumours (p = 0.0038). The irregularity of nuclei was related to TPA positivity, in that the tumours with regular nuclei had higher I values for TPA positivity, than tumours with highly irregular nuclei (p = 0.08). Breast cancer-related survival significantly correlated with TPA positivity as well (p = 0.047). The CEA and CA 50 positivity were not significantly related to clinical or histological variables. Survival could not be predicted significantly by means of CEA or CA 50 quantitation. Our results show that it is possible to quantitate the expression of the tumour markers CEA, TPA and CA 50 in breast cancer in paraffin sections. CEA and CA 50 immunohistochemistry does not possess any significant predictive value in breast cancer, whereas TPA expression might be utilized in discriminating malignant subtypes of breast cancers from the more benign ones.

Antigens, Tumor-Associated, Carbohydrate↗
PubMedDate not supplied

Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer.

S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF also predicted survival in ER+ (p = 0.03) and in PR+ (p = 0.024) tumours. Thus the prognosis of ER+ or PR+ tumours with an SPF less than 9% is favourable with a risk of death of about 20%, in contrast to that of about 70% in tumours with an SPF greater than 9% during the follow-up period. To conclude, the proliferation rate as measured by S phase fraction by FCM is a highly significant prognostic factor in breast cancer. The prognostic value of S phase fraction is confined to steroid receptor-positive tumours, whereas in receptor-negative tumours SPF has no predictive value. The results thus suggest that all women with steroid receptor-negative breast tumours and those receptor-positive tumours with an SPF higher than 9% should be subjected to postoperative adjuvant chemotherapy immediately.

Biomarkers, Tumor↗
PubMedDate not supplied

Reduced alpha- and beta-catenin expression predicts shortened survival in local prostate cancer.

UNLABELLED: The aim of this study was to determine the prognostic value of alpha- and beta-catenin expressions in local prostate cancer (PC). MATERIALS AND METHODS: One hundred and eighty-one PC patients treated with radical prostatectomy were followed-up for a mean of 7.3 years. The alpha- and beta-catenin expression were analysed by immunohistochemistry TMT (tissue microarray technique) and light microscopy. RESULTS: Strong a-catenin expression was related to low Gleason grade (p < 0.001), cancer-free seminal vesicles (p = 0.04) and low preoperative PSA (p = 0.02). Strong beta-catenin expression was related to low Gleason grade (p < 0.001) and cancer-free seminal vesicle status (p = 0.03). Absence of nuclear beta-catenin expression was related to local disease (pT1-T2) (p = 0.05). alpha-catenin (p = 0.06), beta-catenin (p = 0.05), Gleason grade (p = 0.03) and capsular invasion (p = 0.01) were related to PSA recurrence in patients who reached PSA zero postoperatively. PSA recurrence-free survival (RFS) was significantly related to Gleason grade (p < 0.001), capsule invasion (p = 0.01), perineural growth (p = 0.05) and preoperative PSA (p = 0.05). In Cox's analysis, independent predictors of PSA RFS were Gleason grade (p < 0.001) and capsular invasion (p = 0.006). Low expressions of alpha- (p = 0.06) and beta-catenin (p = 0.05) were related to shortened PSA RFS. Survival was related to low alpha- (p = 0.011) and beta-catenin (p = 0.016) expressions. Independent predictors of shortened survival were seminal vesicle invasion (p = 0.016) and low alpha-catenin expression (p = 0.049). CONCLUSION: Reduced alpha- or beta-catenin expressions are related to malignant phenotype in local prostate cancer and predict PSA failure as well as shortened survival.

Humans↗
PubMedDate not supplied

Immunohistochemical demonstration of c-erb B-2 oncoprotein expression in female breast cancer and its prognostic significance.

The expression of c-erb B-2 oncoprotein was studied immunohistochemically in paraffin embedded biopsy specimens of 91 female breast carcinomas. The mean (+/- SD) age of the patients at diagnosis was 59.0 (+/- 13.2) years and they were prospectively followed-up for a mean of 12.4 years (range 11.5-13.3 years). The c-erb B-2 expression was analysed in relation to clinical stage, menopausal status, histological grade, tubular growth pattern, irregularity of nuclei, DNA ploidy and clinical outcome during the follow-up. Grade III tumours showed higher c-erb B-2 expression than low grade tumours and the c-erb B-2 expression than low grade tumours and the c-erb B-2 positivity was also related to the irregularity of the nuclei (p = 0.0815). Crude survival (p = 0.0635) and breast cancer survival (p = 0.072) could be predicted by c-erb B-2 expression, in that the c-erb B-2 negative tumours survived longer. The prediction of crude survival (p = 0.03), breast cancer survival (p = 0.04) and disease-free survival (p = 0.037) was more reliable in postmenopausal women. The results suggest that c-erb B-2 oncogene expression can be used as a prognostic parameter in predicting the biological behaviour of female breast cancer.

Biomarkers, Tumor↗
PubMedDate not supplied

Immunohistochemical staining of human breast cancer with a new tumour marker MCA: relation to axillary lymph node involvement, metastasis, and survival.

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.

Antigens, Neoplasm↗
PubMedDate not supplied

Expression of Ki-67, cyclin D1 and apoptosis markers correlated with survival in prostate cancer patients treated by radical prostatectomy.

OBJECTIVE: The study was designed to analyse the prognostic value of proliferation markers Ki-67 and cyclin D1 and apoptosis in prostate cancer (PC) patients treated by radical prostatectomy. PATIENTS AND METHODS: Two hundred and eleven patients treated by radical prostatectomy for localised prostate cancer were clinically followed up for a mean of 7.3 years. The primary histopathological specimens were re-analysed to ensure uniform histoplthological grading and pT classification. A tissue microarray construction (TMA) was used in immunohistochemisty to assess the expression of Ki-67, cyclin D1 and the apoptosis marker Tag. The results were analysed with light microscopy and the findings were compared to standard histology, pT and clinical follow-up data. RESULTS: The co-expression of Ki-67 and cyclin Dl (p=0.05) was common. High fraction of Ki-67 positive cells and a high fraction of apoptotic cells were often present in same tumours (p=0.05). High apoptotic rate was related to positive surgical margin status (p=0.047). Low expression of Ki-67 was related to a low Gleason score (p<0.001), an absence of either capsule penetration (p = 0.029) or perineural invasion (p=0.004). High expression of cyclin Dl was related to perineural growth (p=0.039). Prostate specific antigen (PSA) recurrence-free survival (RFS) was predicted by Gleason grade (p<0.001) and capsule invasion (p=0.006). High expression of Ki-67 (p=0.03), as well as high apoptotic rate (p=0.04) were related to a high risk of cancer death. In multivariate analysis the seminal vesicle invasion was the only independent predictor of cancer death (p = 0.01). CONCLUSION: The expression of Ki-67, cyclin D1 and a high apoptotic rate are related to a malignant phenotype in prostate cancer, but their prognostic value is inferior to standard histological prognostic factors.

Apoptosis↗
PubMedDate not supplied

The significance of nuclear morphometric variables as prognostic predictors in breast cancer.

The preoperative biopsies from primary breast carcinomas of 504 women were subjected to interactive morphometric analysis of a) the mean nuclear area (NA), b) standard deviation of nuclear area (SDNA), c) mean area of the 10 largest nuclei (NAl0), d) nuclear perimeter (PE), e) standard deviation of nuclear perimeter (SPDE), f) largest nuclear diameter (Dmax) and g) shortest nuclear diameter (Dmin), h) histological grade and i) classical prognostic variables. The above data were correlated with the disease outcome during the mean follow-up period of 11.2 years. Tumor size (p less than 0.0001), morphometric variables (p = 0.0001-0.005) and histological grade (p = 0.03) predicted axillary lymph node metastasis at the time of diagnosis. According to multivariate analysis, tumour size and NA predicted the axillary lymph node metastasis independently. Axillary lymph node status (p less than 0.0001) and histological grade (p = 0.01) predicted the tumour recurrence and recurrence-free survival, whereas the morphometric variables had no significant predictive value. Axillary lymph node status (p less than 0.0001), tumour size (p less than 0.0001), histological grade (p = 0.0012) and morphometric variables (p = 0.003-0.035) predicted the disease-related survival. Of the morphometric variables, NA and the Dmin were the two most important predictors of tumour-related survival in univariate analysis. Dmax had independent prognostic information in multivariate survival analysis. In the same analysis, tumour size and axillary lymph node status were more important predictors. In conclusion, the morphometric variables analysed have independent predictive value in female breast cancer. Their value is, however, inferior to that of the tumour size and axillary lymph node status, but equal to that of the histological grade.

Biopsy↗
PubMedDate not supplied

TAG 12 expression as a prognostic factor in female breast cancer.

The expression of a novel tumour marker TAG 12 was immunohistochemically determined in paraffin embedded biopsies of 79 female breast carcinomas, with special emphasis on its potential prognostic value. The mean (+/- SD) age of the patients at the time of diagnosis was 58.1 (+/- 13.1) years and all women had been prospectively followed-up for a mean of 12.4 years (range 11.5-13.3 years). All except one tumour were TAG 12 positive. In the normal breast, TAG 12 expression was localized at the apical (secretory) cytoplasm of the epithelial cells. Accordingly, TAG 12 was present in abundance in the intraductal secretions as well. TAG 12 positivity was weakly related to histological grade (p = 0.178) and significantly to tubular grade (p = 0.021) of the tumours. TAG 12 positivity was not significantly related to the following parameters: menopausal status, tumour size, axillary lymph node involvement, histological type of the tumour, DNA ploidy, S-phase fraction or irregularity of tumor cell nuclei. The prediction of lymph node involvement and metastasis was not possible in either pre- or postmenopausal women. Similarly, crude survival, breast cancer survival or disease-free survival were not significantly related to TAG 12 expression. The results indicate that quantitation of immunohistochemically determined TAG 12 expression has no prognostic value in breast cancer. At best, TAG 12 might be of some assistance in discriminating malignant breast lesions from benign conditions.

Antigens, Neoplasm↗
PubMedDate not supplied

Hormone receptor status and mitotic activity as risk factors for recurrence and death in female breast carcinoma.

The estrogen (ER) and progesterone (PR) receptor status, volume corrected mitotic index (M/V index) and other classical prognostic factors were related to disease outcome in a series of 281 women with breast cancer followed up for over 8 years. The M/V index predicted recurrence only in ER+ or PR+ patients (p = 0.002-0.006). Similarly, the recurrence-free survival was related to M/V index only in ER+ (p = 0.0005) or PR+ (p less than 0.0001) patients. In survival analysis, ER+ (p = 0.0037) and PR+ (p less than 0.0001) patients were accurately divided into different prognostic groups by the M/V index, whereas in ER- and in PR-tumours the M/V index had only suggestive predictive value (p = 0.06-0.5). In N-tumours the M/V index predicted recurrence-free survival only in ER+ (p = 0.0228) and in PR+ (p = 0.0087) tumours. In survival analysis of N-tumours, the M/V index predicted cancer-related survival in ER+ (p = 0.0102) and in PR+ (p = 0.0014) tumours. In ER-/PR-, N-tumours, none of the variables tested had any prognostic value. The present results suggest that adjuvant hormone treatment might be indicated in ER+ or PR+ tumours with a M/V index greater than 10, regardless of the axillary lymph node status. The prognosis of ER+ or PR+ tumours with a M/V index less than 10 is favourable, the risk of recurrence being of the order of 15% only during the 10-year follow-up. Thus, the expensive and distressing adjuvant treatments could be omitted for these women with an inherently favourable disease outcome.

Breast Neoplasms↗
PubMedDate not supplied

Nuclear morphometry in grading transitional cell bladder cancer compared with subjective histological grading.

A retrospective study was performed comprising 265 bladder cancer patients. The patients were clinically followed up for an average of 10 years. The initial tumour biopsies were subjected to morphometric analysis. The mean nuclear area (NA), the standard deviation of nuclear area (SDNA) and the mean area of the 10 largest nuclei (NA10) were measured using IBAS 1&2 image analyzer. The prognostic value of NA, SDNA, NA10, papillary, subjective histological grading (WHO) and clinical stage (UICC) was evaluated. The progress in T-category was related to histological grade (p less than 0.0001), non-papillar growth (p = 0.0023), SDNA (p = 0.0110) and NA10 (p = 0.0305), in that order. The same parameters in addition to NA predicted lymph node involvement and metastasis. Recurrence rate was significantly related to NA10 (p = 0.0250). Non-papillar growth (p = 0.002), clinical stage (p = 0.005), histological grade (p = 0.0120), NA (p = 0.0143), SDNA (0.0383) and NA10 (p = 0.0632) predicted recurrence-free period. Bladder cancer survival was related to clinical stage (p less than 0.0001), histological grade (p less than 0.0001), SDNA (p less than 0.0001), non-papillar growth (p less than 0.0001), NA (p = 0.0001) and NA 10 (p = 0.0001), in that order. Grade II tumours could be regrouped prognostically using NA (p = 0.006), SDNA (p = 0.033) and NA10 (p = 0.016) as classifiers. Clinical stage, NA and histological grade predicted bladder cancer survival in a multiparameter analysis. The results show that NA and SDNA are powerful prognosticators of survival. NA10 and SDNA predict progression better than NA. The multiparameter analysis identified clinical stage, histological grade and NA as the most important prognosticators of survival.

Analysis of Variance↗
PubMedDate not supplied

Prognostic value of cathepsin-D expression in female breast cancer.

Expression of an acidic lysosomal protease, cathepsin-D (CD), was analysed immunohistochemically in a series of 151 breast carcinomas with special reference to its prognostic significance, Strong expression of CD was detected in 22% of cases. This intense expression was significantly associated with a number of established prognostic factors, including the non-ductal type of carcinoma (p = 0.0243) and metastases at the time of diagnosis (p = 0.0068). On the other hand, high expression of CD was not related to the lymph-node status, tumour size, ER/PR content or histological grade. Patients with CD overexpression has a significantly lower survival probability (p = 0.0478) than did the patients with low expression of this protease. The relationship between the high expression of CD and short disease-free survival was almost significant (p = 0.0519). Intense immunostaining of CD was associated with a significantly impaired disease outlook in patients with confirmed lymph node metastasis (N+) (p = 0.0137) but not in those with negative lymph nodes (N-) (p = 0.0620). In Cox's multivariate analysis, expression of CD had no independent prognostic value over the conventional prognostic factors. The results suggest that expression of CD is of borderline significance in evaluating the intrinsic malignancy of female breast cancer in general. The potential of CD as a prognostic factor in specific subgroups of breast cancers will be the subject of further studies.

Breast Neoplasms↗