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Biomedical subjects

S Toikkanen

Publications and source records attributed to S Toikkanen.

At least 19 recordsLinked to original sources
PubMed2001

Algorithmic 3D simulation of breast calcifications for digital mammography.

We present a framework for algorithmic three-dimensional simulation of breast calcifications. The simulated calcifications can be viewed from any angle at a higher spatial resolution than currently available for digital mammography, and they can be placed onto a simulated or real mammographic background to provide example cases for computers and radiologists. In order to simulate calcification clusters, we also show how to simulate duct networks and terminal ductal lobular units. We evaluated the model with a double-blind evaluation of 60 cases with four experienced radiologists by mixing 30 cases of simulated calcification clusters on a real or simulated mammographic background with 30 cases of real breast calcification clusters digitized at a spatial resolution of 15 microm from high-resolution radiographs of 5 mm slices of breast specimens. The results indicate that the majority of the 2D projections of the 3D simulated calcifications compare favorably with the radiographic images of real breast calcifications.

Algorithms↗
PubMed2000

Expression of estrogen receptor (ER) in oral mucosa and salivary glands.

OBJECTIVES: To assess the expression of estrogen receptor (ER) in oral mucosa and salivary glands, buccal mucosal biopsies from ten postmenopausal women (taken before and during the hormone replacement therapy), as well as, single biopsies from 20 healthy 19-year-old women were analyzed for ER expression. Salivary gland biopsies were taken from the minor labial salivary glands (n=6), submandibular glands (n=5) and parotid gland (n=1) from women at different ages. METHODS: total RNA extracted from the tissue samples was reverse-transcripted (RT) to single-stranded cDNA, and the RT-polymerase chain reaction (RT-PCR) product was subjected to nucleotide sequencing to confirm the match with ER cDNA. Immunohistochemistry (IHC) with a monoclonal ER antibody (ER-ICA, Abbott) and Western blot analysis with monoclonal antibody against ER-related antigen (ER-D5, Amersham) were performed on the biopsies taken from the postmenopausal women. RESULTS: ER mRNA was expressed in 18/20 (90%) and 20/20 (100%) of the mucosal biopsies in the postmenopausal and 19-year-old women, respectively. The expression of mRNA was detected in all the submandibular gland samples, in the single parotid gland, as well as, in 4/6 (67%) of the labial glands. ER expression could not be detected by IHC, indicating either a very low level of expressed protein or difficulties in recognizing the epitopes by IHC. However, Western blot demonstrated 8/8 (100%) of the mucosal biopsies of postmenopausal women positive for ER-related antigen. CONCLUSIONS: the presence of ER mRNA and immunoreactive ER protein suggests that estrogens have a biological role in oral mucosa and salivary glands.

Antibodies, Monoclonal↗
PubMed2000

Comparison of the effects of tamoxifen and toremifene on rat hepatocarcinogenesis.

The hepatoproliferative and cytochrome P450 enzyme inducing effects of two antiestrogens, tamoxifen and toremifene, were compared in female Sprague-Dawley rats using immunohistochemical staining methods. Equimolar doses of the antiestrogens (tamoxifen 45 mg/kg and toremifene 48 mg/kg) were given by oral administration to 6-week-old rats for 12 months including a 3-month recovery period. Controls received the vehicle carboxymethylcellulose. Altogether 90 rats were used in the study. Five rats per dose group were killed after 14 days, 5 weeks, 3, 6 and 12 months of treatment as well as after the 3-month recovery period. Hepatocellular carcinoma was found in four out of five rats after 12 months of tamoxifen treatment. After the 3-month recovery period all tamoxifen-treated rats had large liver tumors (diameter up to 3 cm). No tumors were observed in toremifene-treated rats. Liver cell proliferation was measured by the index of proliferating cell nuclear antigen (PCNA) expression. Immunohistochemical staining with the placental form of glutathione S-transferase (GST-P) was used as a marker for preneoplastic foci. Cytochrome P450 induction was measured using specific antibodies to isoenzymes. Tamoxifen increased the incidence of GST-P-positive foci significantly by 3 months of treatment but toremifene did not as compared with the controls. Liver cell proliferation increased significantly only in the liver tumors of tamoxifen-treated rats after 12 months of treatment and during the recovery period. Both antiestrogens induced the isoenzymes CYP2B1/2 and CYP3A1 within 14 days although tamoxifen was a more powerful inducer. Immunohistochemistry of rat liver sections showed a centrilobular localization of these induced enzyme proteins. The expression of CYP2B1/2 and 3A1 could also be observed in foci after 3 and 6 months of administration and in liver adenomas and in some carcinomas after 12 months of administration with tamoxifen. The results show that tamoxifen, but not toremifene, has the potential to induce and promote the development of rat hepatocarcinogenesis in this experimental model.

Animals↗
PubMed1999

Late mortality from pT1N0M0 breast carcinoma.

BACKGROUND: pT1N0M0 breast carcinoma (< or = 2 cm in greatest dimension, lymph node negative) is associated with generally favorable 5-year and 10-year survival, but to the authors' knowledge there are few data available regarding the long term outcome of these patients. METHODS: The authors identified women with breast carcinoma diagnosed between 1945-1984 in a geographically defined urban population using the files of the Finnish Cancer Registry and local hospital records (n = 1495). The clinical and autopsy records and histologic slides were reviewed. The series contained 265 patients with unilateral pT1N0M0 breast carcinoma treated with mastectomy and axillary lymph node dissection without adjuvant systemic therapy and who were followed for 10-44 years (median, 17 years) after the initial diagnosis or until death. RESULTS: The last death from pT1N0M0 breast carcinoma occurred 23 years after the initial diagnosis. The 20-year overall survival rate was 54% (95% confidence interval [95% CI], 48-60%) and the survival rate when corrected for intercurrent deaths was 81% (95% CI, 75-87%). The 20-year survival rate when corrected for intercurrent deaths was 92% (95% CI, 86-98%) in patients with T1a-b disease (primary tumor < or = 10 mm), but was only 75% (95% CI, 64-86%) in patients with pTc disease (range, 11-20 mm). None of the patients with well differentiated (World Health Organization Grade 1) pTa-b tumors died of breast carcinoma (n = 48) whereas the 20-year survival rate when corrected for intercurrent deaths was 81% (95% CI, 67-95%) in patients with Grade 2-3, pT1a-b tumors (P = 0.002). CONCLUSIONS: Patients with well differentiated pT1a-b tumors form a subgroup with excellent long term prognosis, but a significant proportion of women with either moderately or poorly differentiated pT1a-b tumors or pT1c tumors ultimately die of the disease.

Adult↗
PubMed1999

Artificial neural networks applied to survival prediction in breast cancer.

In this study, we evaluated the accuracy of a neural network in predicting 5-, 10- and 15-year breast-cancer-specific survival. A series of 951 breast cancer patients was divided into a training set of 651 and a validation set of 300 patients. Eight variables were entered as input to the network: tumor size, axillary nodal status, histological type, mitotic count, nuclear pleomorphism, tubule formation, tumor necrosis and age. The area under the ROC curve (AUC) was used as a measure of accuracy of the prediction models in generating survival estimates for the patients in the independent validation set. The AUC values of the neural network models for 5-, 10- and 15-year breast-cancer-specific survival were 0.909, 0.886 and 0.883, respectively. The corresponding AUC values for logistic regression were 0.897, 0.862 and 0.858. Axillary lymph node status (N0 vs. N+) predicted 5-year survival with a specificity of 71% and a sensitivity of 77%. The sensitivity of the neural network model was 91% at this specificity level. The rate of false predictions at 5 years was 82/300 for nodal status and 40/300 for the neural network. When nodal status was excluded from the neural network model, the rate of false predictions increased only to 49/300 (AUC 0. 877). An artificial neural network is very accurate in the 5-, 10- and 15-year breast-cancer-specific survival prediction. The consistently high accuracy over time and the good predictive performance of a network trained without information on nodal status demonstrate that neural networks can be important tools for cancer survival prediction.

Adult↗
PubMed1998

Long-term survival in node-positive breast cancer treated by locoregional therapy alone.

To investigate the long-term survival rate of node-positive (pN+) breast cancer treated by locoregional therapy alone, we made an attempt to identify all such patients followed up for at least 15 years after treatment in a defined geographical area (city of Turku, Southwestern Finland) and time period (1945-79) using the files of the local hospitals and the Finnish Cancer Registry. The clinical and autopsy records and histological slides of 1172 women diagnosed with breast cancer in the city were reviewed. From this cohort we identified 339 women with unilateral node-positive breast cancer treated with locoregional therapy without systemic adjuvant therapy. The relative survival rate of the cohort compared with the general female population matched for age and year of follow-up was calculated. The 15- and 30-year survival rates corrected for known intercurrent deaths were 26% (95% CI, 21-31%) and 21% (16-26%) respectively, and the relative survival rates 23% and 21% respectively. None of the patients with pN2 disease survived for 15 years, whereas the 30-year corrected survival rate in pN1 disease was 24% (18-30%). Women with pT1N1M0 cancer had as high as 59% (43-75%) 15-year survival rate corrected for intercurrent deaths. A trend for improving survival was found by the decade of diagnosis. The results indicate that a considerable proportion of women with pN1 breast carcinoma treated with locoregional therapy alone become 30-year survivors and are probably cured. Adequate locoregional treatment is mandatory in the care of node-positive breast cancer.

Adult↗
PubMed1998

MR and magnetisation transfer imaging in cirrhotic and fatty livers.

PURPOSE: To determine whether low-field MR fat/water separation and magnetisation transfer (MT) techniques are useful in studying the livers of patients with parenchymal liver diseases in vivo. MATERIAL AND METHODS: MR and MT imaging of the liver in 33 patients (14 with primary biliary cirrhosis, 15 with alcohol-induced liver disease, and 4 with fatty liver) was performed by means of the fat/water separation technique at 0.1 T. The relaxation time T1 and the MT contrast (MTC) parameter of liver and spleen tissue were measured, and the relative proton density fat content N(%) and MTC of the liver were calculated from the separate fat and water images. The value of N(%) was also compared with the percentage of fatty hepatocytes at histology. RESULTS: The relaxation rate R1 of liver measured from the magnitude image, and the difference in the value of MTC measured from the water image compared with the one measured from the fat and water magnitude image, both depended linearly on the value of N(%). The value of N(%) correlated significantly with the percentage of the fatty hepatocytes. In in vivo fatty tissue, fat infiltration increased both the observed relaxation rate R1 and the measured magnetisation ratio (the steady state magnetisation MS divided by the equilibrium magnetisation MO, MS/MO) and consequently decreased the MT efficiency measured in a magnitude MR image. The amount of liver fibrosis did not correlate with the value of MTC measured after fat separation. CONCLUSION: Our results in studying fatty livers with MR imaging and the MT method show that the fat/water separation gives more reliable parametric results. Characterisation of liver cirrhosis by means of the MTC parameter is not reliable, even after fat separation.

Adult↗
PubMed1997

Mammography screening interval and the frequency of interval cancers in a population-based screening.

In a population-based mammography screening, 129,731 examinations were carried out among 36,000 women aged 40-74 in the city of Turku, Finland, in the period 1987-94. Women older than 50 were screened at 2-year intervals, and those younger than 50 at either 1-year or 3-year intervals, depending on their year of birth. Screen-detected breast cancers numbered 385 and, during the same time period, 154 women were diagnosed with breast cancer outside screening in the same age group in the same city, and 100 interval cancers were detected. Two hundred and fifty (67%) of the screen-detected cancers were of post-surgical stage I compared with 45 (45%) of the interval cancers and 52 (34%) of the cancers found outside screening (P<0.0001). However, among women aged 40-49 the frequency of stage I cancers did not differ significantly among screen-detected cancers, interval cancers and cancers found outside screening (50%, 42% and 44% respectively; P=0.73). Invasive interval cancers were more frequent among women aged 40-49 if screening was done at either 1-year (27%) or 3-year intervals (39%) than in older women screened at 2-year intervals (18%; P=0.08 and P=0.0009 respectively). Even if adjusted for the primary tumour size, screen-detected cancers had smaller S-phase fractions than interval cancers or control cancers (P=0.01), but no difference in the S-phase fraction size was found between cancers of women younger than 50 and those older than this (P=0.13). We conclude that more interval cancers were found among women younger than 50 than among those older than 50 and that this could not be explained by the rate of cancer cell proliferation.

Adult↗
PubMed1997

Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.

The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.

Adult↗
PubMed1996

Standardized mitotic counts in breast cancer. Evaluation of the method.

Twenty-one pathologists and technicians participated in a study evaluating the variation present in mitotic counts for prognostication of breast cancer. The participants counted the mitotic figures in 20 breast cancer samples from ten high power fields (mitotic activity index, MAI, giving the results in mitotic figures per 10 fields) and also made a correction for field size and area fraction of the neoplastic epithelium to get the standardized mitotic index (volume fraction corrected mitotic index, or M/VV index, giving the result in mitotic figures per square mm of neoplastic epithelium). The difference in variation between the two methods was not big, but the standardized mitotic index (SMI) showed consistently smaller variation among all participants and different subgroups. Experienced pathologists had the highest variation in mitotic counts, and specially trained technicians, the lowest. The efficiency of the mitotic counts in grading (the grading efficiency) was used to evaluate the mitotic counts. In groups without special training for mitotic counts the mean grading efficiency was lower (experienced and training pathologists both on average had the potential to grade 88% of the cases correctly) than in the group specially trained for the purpose (trained technicians had the potential to grade 95% of the cases correctly). Among the specially trained technicians, the grading efficiency was of the same magnitude as the grading efficiency achieved in determining the S-Phase fraction of cells from paraffin embedded breast cancers by flow cytometry in different laboratories. The results suggest that special training is helpful in making mitotic counts more reproducible, and that in trained hands, the mitotic counts give results comparable to more sophisticated methods of determining proliferative activity in breast cancer.

Breast Neoplasms↗
PubMed1995

Stromal cell cathepsin D expression and long-term survival in breast cancer.

Breast cancers with an increased level of cathepsin D in tumour tissue extract have been found to have poor prognosis, but studies performed with immunohistochemistry have produced variable results. We analysed 213 primary invasive breast cancers for cathepsin D expression from archival tissue with immunohistochemistry. The minimum follow-up of the patients still alive was 26 years. Women with ductal cancer that lacked cathepsin D expression in stromal macrophage-like cells had a 75% 5 year and 55% 30 year survival rate as compared with only a 40% 5 year and 20% 30 year survival rate if stromal cells expressed cathepsin D (P = 0.0003), whereas cathepsin D expression of cancer cells was associated with neither survival nor the several prognostic factors investigated. Stromal cell cathepsin D was more often present in the ductal than in the lobular histological type (80% vs 54%, P = 0.002), and its expression was strongly associated particularly with a high cell proliferation rate. However, in a multivariate analysis stromal cell cathepsin D expression did not have independent influence on survival in the entire series. We conclude that high stromal cell cathepsin D expression is associated with a poor short- and long-term outcome in breast cancer.

Adult↗
PubMed1995

Cured of breast cancer?

PURPOSE: That patients can be ultimately cured of breast cancer has been questioned, because late deaths from the disease have been observed even several decades after the diagnosis. The purpose of this study was to investigate late mortality caused by breast cancer. PATIENTS AND METHODS: Using the files of local hospitals and the Finnish Cancer Registry, we identified all patients with histologically diagnosed invasive breast cancer in a defined urban area (city of Turku, Finland) from 1945 to 1969 (n = 601). In 563 cases (94%), clinical data and histologic and autopsy slides could be reviewed, and these women had been monitored for a median of 29 years (range, 22 to 44; n = 66) or until death (n = 497). RESULTS: Mortality from breast cancer was observed even during the fourth follow-up decade, but if women who were diagnosed with contralateral breast cancer were excluded (n = 30), no deaths from breast cancer were identified after the 27th year of follow-up evaluation. The 30-year survival rates were 62% (95% confidence interval [CI], 54% to 70%), 19% (95% CI, 13% to 25%), and 0% for women with pN0 (node-negative) and pN1 or pN2 (node-positive) disease, respectively. High 30-year survival rates were found in small (pT1N0M0) unilateral cancers (80% alive; 95% CI, 66 to 94%), and in the lobular (45% alive; 95% CI, 31% to 59%) and the special histologic types (81% alive; 95% CI, 67% to 95%). These survival rates were obtained when correcting either for known intercurrent deaths or for mortality in the age- and sex-matched general population. CONCLUSION: Breast cancer, node-negative and node-positive, may be permanently cured even if treated with locoregional therapy only. The survival figures listed here may be considered as minimum values, because women with breast cancer diagnosed in the same area from 1970 to 1984 showed significantly improved short-term (< 20 years) survival rates over those diagnosed from 1945 to 1969.

Adult↗
PubMed1994

Bcl-2 protein expression and long-term survival in breast cancer.

Bcl-2 gene product functions to prevent apoptosis in a variety of in vitro and in vivo experiments. The prognostic significance of Bcl-2 protein expression was investigated by immunocytochemistry from paraffin-embedded tissue in a series of 174 women with breast cancer, treated with radical surgery with or without regional radiotherapy, and who had been followed up for the median of 31 years or until death. A minority (25%) of cancers were entirely negative for Bcl-2 protein. Moderate to strong Bcl-2 protein expression (present in 46%) was strongly associated with several favorable prognostic features, such as a low mitotic count, high histological grade of differentiation, and lack of p53 protein expression (P < 0.0001 for each). It was also significantly associated with lack of tumor necrosis, a low S-phase fraction size, low cathepsin D expression, DNA diploidy, and the lobular histological type, but not with the primary tumor size or the axillary nodal status. Women with cancer with moderate to strong Bcl-2 protein expression had more favorable short-term (69% versus 46% alive at 5 years) but similar long-term (29% versus 33% alive at 30 years) disease-specific survival as those with cancer with weak or lacking expression. Bcl-2 protein expression did not have independent prognostic value in a multivariate survival analysis. We conclude that Bcl-2 protein is frequently expressed in breast cancer, and its expression is associated with favorable clinicopathological features.

Adult↗
PubMed1994

Association of steroid hormone receptor content and flow cytometric DNA ploidy in endometrial carcinoma.

Flow cytometric DNA ploidy and sex steroid hormone receptor activity was measured in 55 endometrial carcinomas. DNA ploidy was measured on paraffin-embedded specimens and ER and PR activity was measured using both biochemical and immunohistochemical assay. Association of these parameters was tested using logistic regression model. Diploid or near diploid DNA histogram was seen in 40 cases (72.7%). All Grade 1 tumours (n = 15) were diploid whereas 38.5% of Grade 2 (n = 27) and Grade 3 (n = 13) tumours were aneuploid (grade 1 vs Grade 2 and 3, P = 0.0031). The mean value of ER was 109 +/- 120 (SD) fmol/mg protein for diploid tumours and 48 +/- 50 fmol/mg protein for aneuploid tumours (P = 0.0093). The corresponding values for PR were 226 +/- 262 fmol/mg protein and 75 +/- 102 fmol/mg protein (P = 0.0073), respectively. In immunohistochemical assay the mean HSCORE of ER was 45 +/- 77 for diploid tumours and 27 +/- 48 for aneuploid tumours (P = 0.43). The corresponding values for PR were 32 +/- 55 and 22 +/- 56, respectively (P = 0.58). In logistic regression analysis cytosolic PR content was associated with DNA ploidy.

Adult↗
PubMed1994

Steroid hormone receptors and flow cytometric DNA ploidy in ovarian carcinoma.

The biochemical and immunohistochemical estrogen (ER) and progesterone receptor (PR) content and flow cytometric DNA ploidy was analyzed in five semimalignant and 35 malignant epithelial ovarian tumours. By biochemical assay, 67% of the tumours were ER-positive (> or = 5 fmol/mg protein) and 56% were PR-positive (> or = 10 fmol/mg protein). The corresponding values by immunohistochemical assay (with a HSCORE of 10 as the cutoff level) were 22% and 27%, respectively. DNA histogram measured from paraffin embedded specimens were diploid in 20% (7/35) and aneuploid in 80% (28/35) of the malignant tumours. All semimalignant tumours were diploid. The mean receptor values in the diploid and aneuploid tumours did not differ significantly and receptor-positive and receptor-negative tumours were evenly distributed in all stages and grades. In contrast, flow cytometric DNA ploidy was clearly associated with tumour stage (G2 = 10.52, Df = 3, P = 0.015) and histological differentiation (G2 = 20.57, Df = 3, P = 0.0001).

Adult↗
PubMed1993

AgNOR counts have no prognostic value in breast cancer.

The prognostic significance of silver-stained nucleolar organizer regions (AgNORs) was retrospectively studied among 230 patients with operable invasive breast cancer from a defined urban population. The number of AgNORs was evaluated from routinely processed paraffin sections by light microscopy at a total magnification of x630. The number of AgNORs had no predictive value on the 8-year survival rate corrected for intercurrent deaths (P = 0.2). A high number of AgNORs (> 2.7, the median value) was not related to any other prognostic variable studied except a low S-phase fraction measured by flow cytometry. AgNOR counting does not appear to be a useful prognostic variable in breast cancer.

Breast Neoplasms↗