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T Kuopio

Publications and source records attributed to T Kuopio.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cysteine proteinase inhibitor cystatin A in breast cancer.

Cystatin A (acid cysteine proteinase inhibitor; ACPI) is a natural inhibitor of cysteine proteinases. It has been suggested that an inverse correlation exists between cystatin A and malignant progression. We wanted to assess the biological and clinical significance of cystatin A in infiltrative breast carcinoma by immunohistochemical staining. Formalin-fixed paraffin-embedded material from 440 cases treated during the years 1988-1991 was used in the study. After exclusion of patients with disseminated disease at diagnosis, previous contralateral breast carcinoma, and absence of follow-up data, 384 patients could be included in the survival analysis. For immunohistochemical analysis of cystatin A, we used monoclonal cystatin A antibody WR-23/2/3/3, the binding of which was detected by the avidin-biotin-peroxidase method. Immunohistochemical analysis of Bcl-2 and p53 was also done, and mitotic activity was evaluated. Positive staining for cystatin A was found in 52 of 440 cases. The staining was irregular but showed irrefutably positive areas within neoplastic tissue. Most of the positive tumors were of the ductal infiltrative type, but two were mucinous carcinomas, one medullary and one squamous cell carcinoma. No lobular carcinomas showed positive staining. Focal cystatin A positivity was seen in myoepithelial cells of benign ducts. Occasional apoptotic bodies within the neoplasm showed strong positivity for cystatin A. Tumors positive for cystatin A were of larger size and had higher mitotic activity than cystatin A-negative tumors. Cystatin A was associated with negative Bcl-2 staining, but there was no statistically significant association between axillary lymph node status or p53 immunostaining. The risk for breast cancer-related death was significantly higher in patients with cystatin A-positive tumors than in those with cystatin A-negative ones. The risk increase was significant also in lymph node-negative patients. After adjusting for the effect of tumor size, histological grade, and lymph node status, cystatin A-positive patients still had a higher risk of death. Patients with cystatin A and p53 coexpression had a higher risk of death than the other patients. The findings reveal a new variant of aggressive breast cancer. This type of carcinoma may develop during tumor progression through genetic instability that allows cystatin A expression and gives growth advantage to a clone of tumor cells.

Adenocarcinoma, Mucinous↗
PubMed1998

Morphometric grading in breast cancer: thresholds for mitotic counts.

Three hundred sixty-four cases of invasive ductal breast cancer diagnosed during the years 1988 to 1991 were analyzed to determine quantitative thresholds for mitotic activity. Mitotic counts were calculated in each sample and expressed as standardized mitotic index (SMI) and mitotic activity index (MAI). Based on Kaplan-Meier curves, univariate and multivariate analysis of Cox's regression, and maximum efficiencies of ROC analysis, optimal thresholds were determined on the basis of survival and recurrence of disease. In our material, with a follow-up time of 5 years 9 months, we found two thresholds--a lower and a higher--for both SMI (17 mitoses/mm2 and 32 mitoses/mm2) and MAI (13 mitoses/10 HPF and 35 mitoses/10 HPF). The thresholds were the same in the whole material and in subgroups divided according to the patients' age and axillary lymph node status at the time of diagnosis, and tumor size. The thresholds clearly separated patients with favorable, intermediate, and unfavourable outcome of disease. In our material, the risk of breast cancer death associated with the determined thresholds (ranging from 4.7 to 3.8) clearly exceeded those of menopausal status, axillary lymph node status and tumor size. The risk of breast cancer death associated with the determined thresholds was still emphasized in the groups of premenopausal and axillary lymph node-negative patients, and with tumor size less than 2 cm in diameter (risk ratios, 11.8, 6.0, and 6.7, respectively). The results suggest that the presented quantitative thresholds could be applied in grading of invasive ductal breast cancer.

Adult↗
PubMed1998

Morphometric grading of invasive ductal breast cancer. I. Thresholds for nuclear grade.

We analysed 170 histological samples of invasive ductal breast cancer from years 1988-91 by computerized nuclear morphometry, to find objective and quantitative thresholds for nuclear grade. Based on Kaplan-Meier curves reflecting survival and recurrence of disease and univariate analysis by Cox's regression, optimal thresholds were determined for features related to nuclear size and size variation. In our material, with mean follow-up time of 5 years 9 months, the determined thresholds for nuclear profile area (32 microm2 and 47 microm2), nuclear diameter (6.4 microm and 7.4 microm) and mean shortest nuclear axis (4.8 microm and 6.4 microm) best separated the cases with favourable, intermediate and unfavourable course of disease. In this material from the era of mammography and adjuvant therapy, the mean shortest nuclear axis was found to be a significant prognostic factor, with a risk ratio (RR) exceeded only by that of tumour size (RRs 2.9- and 3.5-fold respectively). The results suggest that morphometric grading criteria can be developed for application in Bloom-Richardson grading and in the Nottingham Prognostic Index.

Adult↗
PubMed1997

The reproducibility of nuclear morphometric measurements in invasive breast carcinoma.

The intraobserver and interobserver reproducibility of computerized nuclear morphometry was determined in repeated measurements of 212 samples of invasive breast cancer. The influence of biological variation and the selection of the measurement area was also tested. Morphometrically determined mean nuclear profile area (Pearson's r 0.89, grading efficiency (GE) 0.95) and standard deviation (SD) of nuclear profile area (Pearson's r 0.84, GE 0.89) showed high reproducibility. In this respect, nuclear morphometry equals with other established methods of quantitative pathology and exceeds the results of subjective grading of nuclear atypia in invasive breast cancer. A training period of eight days was sufficient to produce clear improvement in consistency of nuclear morphometry results. By estimating the sources of variation it could be shown that the variation associated with the measurement procedure itself is small. Instead, sample associated variation is responsible for the majority of variation in the measurements (82.9% in mean nuclear profile area and 65.9% in SD of nuclear profile area). This study points out that when standardized methods are applied computerized morphometry is a reproducible and reliable method of assessing nuclear atypia in invasive breast cancer. For further improvement special emphasize should be put on sampling rules of selecting the microscope fields and measurement areas.

Breast Neoplasms↗
PubMed1997

PROGNOSTICATION OF BREAST CANCER BY MULTIVARIATE METHODS.

Three multivariate prognostic models based on Cox's regression were tested in terms of how they predicted prognosis in a material of 134 patients with breast cancer. The multivariate models all incorporated tumor size, mitotic activity index (MAI), and axillary lymph node status in their formulas, and were originally produced through studies on different patient materials. The predictive behavior of MAI was also tested separately in the same material. The multivariate models gave roughly parallel predicted percentages of survival at two years (CV=5.2%), but showed clearly greater variation later (12.3% and 24.4% at 5 and 9 years, respectively). The results were more uniform between the multivariate models, than between the prediction by MAI and the multivariate models. The variation between repeated estimates was smaller within multivariate models than within the estimation of one of their components (MAI). We found the use of the multivariate models easy. However, traditional hospital practice does not necessarily favor the use of multivariate models, although they seem to group patients more reliably than single prognostic features.

Journal Article↗
PubMed1997

Subjective breast cancer grading. Analyses of reproducibility after application of Bayesian belief networks.

OBJECTIVE: To examine the influence of Bayesian belief networks (BBNs) on the reproducibility of subjective breast cancer grading. STUDY DESIGN: Twenty samples were analyzed for intraobserver and 128 samples for interobserver reproducibility using the Bloom-Richardson and Helpap grading systems. The expression of diagnostic features was evaluated subjectively, and for each a decision it was determined to what extent it represented one of the different outcomes. Evidence was then entered, for each diagnostic feature, into four different BBNs, recently described for breast cancer grading, in the form of a relative likelihood ratio vector. RESULTS: With all cases considered, the use of decision support based on the Bloom-Richardson and Helpap grading systems did not improve intraobserver reproducibility. This was found to be 68% and 80% in subjective gradings, respectively, and 60% and 70% in the BBN-supported method. Interobserver reproducibility was not improved (58% and 70% in subjective gradings and 51-59% based on assessment with decision support). However, when only cases associated with high beliefs were considered, both intraobserver reproducibility (agreement rose from 68% to 93%) and interobserver reproducibility (agreement rose from 60% to 87%) of BBN-supported gradings exceeded the results of subjective assessments. CONCLUSION: The results showed that the observers did not reach the same diagnosis (or grade) and that their observational assessment of histologic features lacked agreement. Since BBNs reflected only the data entered, poor agreement existed in the contribution to the final diagnostic belief by the different features and, ultimately, in belief in the final decision.

Bayes Theorem↗
PubMed1996

Mitotic count in breast cancer. The influence of training on performance.

Two medical laboratory histotechnologists were trained on mitotic counting for 6 months and 1 year. The training included detailed theoretical education on mitotic counts and microscopy sessions with a motivated pathologist. Most of the training time, however, was used for mitotic counts from a large collection of breast cancer samples. The progress in performance was followed by allowing the technicians to count 20 breast cancer samples several times during the training. The mean value of the mitotic counts of technician 1 varied dramatically during the early phases of training but then stabilized near the levels of technician 2, whose mean values were more constant throughout the training period. Both observers showed changes in the standard deviation and coefficient of variation in the early phases of training but later stabilized at the same level. The proportion of the counting results of the technicians within the 95% confidence limits determined by the performance of already trained, experienced technicians varied considerably at first, but then stabilized at values 0.7 and above. The study showed that training improved the performance in mitotic counting. We suggest that the training of mitotic counts provides the means to achieve economical and reproducible estimates of tumor cell proliferation.

Breast Neoplasms↗
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↗
PubMed1996

Immunohistochemical labelling for prostate specific antigen in non-prostatic tissues.

Immunohistochemical detection of prostate specific antigen (PSA) in metastases of adenocarcinomas is widely used as an aid to identify the prostatic origin of metastatic cells. However, on the one hand, PSA may not be expressed in some poorly differentiated prostatic carcinomas, while on the other, PSA immunoreactivity has been found in small amounts in non-prostatic tissues. The aim of the current study was to evaluate the prevalence of PSA immunoreactivity in normal non-prostatic tissues and in breast carcinoma. PSA was localized by immunohistochemistry with four commercial antibodies in 34 different normal human tissues, and in 15 ductal and seven apocrine breast carcinomas. Concentrations of PSA in tissue homogenates of prostate and nine non-prostatic tissues from autopsied subjects were measured by a two-site immunoradiometric assay. Weak PSA immunoreactivity was found by immunohistochemistry in kidney, parotid gland and pancreatic tissues. Variable PSA immunoreactivity was seen in three cases of ductal (20%) and two cases of apocrine breast carcinoma (28%). No consistent PSA immunoreactivity was found in homogenates of non-prostatic tissues by the immunoradiometric assay. We conclude that PSA is a quite specific marker of prostatic tissue. However, there are some non-prostatic neoplastic and normal tissues that express PSA. Therefore, a definite diagnosis of metastasis of prostatic origin cannot be made on the basis of immunolabelling for PSA alone.

Antibodies, Neoplasm↗
PubMed1995

Acinar cell carcinoma of the pancreas. Report of three cases.

Pancreatic acinar cell carcinoma is a rare neoplasm (comprising about 1% of pancreatic tumours). We studied three cases (61-year-old female; 42-year-old male; 57-year-old male), whose survival after diagnosis ranged from 1 year 2 months to 6 years 8 months. There were widespread metastases in each case. The tumours had acinar, trabecular and solid growth patterns. By immunohistochemistry, pancreatic acinar cell markers including carboxyl ester lipase, pancreatic secretory trypsin inhibitor and pancreatic phospholipase A2 (group I PLA2) gave a strong positive reaction in all three cases. By electron microscopy, zymogen granules were seen in the cytoplasm of the tumour cells. Immunostaining for prostate-specific antigen was positive in all three cases. Above-normal concentrations of pancreatic PLA2 were measured in the serum of one patient and the values decreased during chemotherapy concomitantly with the reduction in the size of the tumour mass. In conclusion, immunohistochemical demonstration of the secretory products of acinar cells including the new marker pancreatic PLA2 is useful in the differential diagnosis of pancreatic acinar cell carcinoma. Determination of the concentration of pancreatic group I PLA2 in serum may be helpful in the evaluation of therapy.

Adult↗
PubMed1995

Nuclear morphometry in differential diagnosis of renal oncocytoma and renal cell carcinoma.

PURPOSE: Morphometric distinction of renal oncocytoma and renal cell carcinoma was attempted. MATERIALS AND METHODS: Nuclear morphometric measurements were done from sections of 16 histologically diagnosed renal oncocytomas and renal cell carcinoma controls (grade 1 or 2, stage T1 to 2N0M0). RESULTS: Oncocytomas could be distinguished from carcinomas on the basis of nuclear morphometry in more than 80% of the cases. Especially, the shape descriptors (form factors) were significantly different between oncocytomas and carcinomas. CONCLUSIONS: Morphometrically determined nuclear shape descriptors can be used to support diagnostic decisions in problematic cases.

Adenoma, Oxyphilic↗
PubMed1995

Nuclear morphometry in breast cancer: the influence of sampling rules and freezing of samples.

We studied nuclear morphometry of human breast cancer with special emphasis on two sources of variation: freezing prior to fixation and selection of measured objects on the basis of different sampling rules. Samples of 147 histologically verified invasive breast cancer cases were examined with a computer-based image overlay drawing system. Thirty-eight of the 147 samples of tissue frozen before embedding in paraffin were analyzed separately. Among the latter we found shrinkage of 35% and 46% (depending on the sampling rule) of the nuclear profile area as compared with samples not frozen before the standard tissue processing. These findings confirm that nuclear morphometry results from frozen and unfrozen tissue are not comparable. Frozen tissue later embedded in paraffin should not be used with prognostication models based on traditionally fixed tissue. In morphometry we applied two sampling rules that differed in the criteria used for selecting nuclei for measurement. We registered a significant difference in nuclear size and in the variation of nuclear size between the two sampling methods. Of the morphometric features studied, nuclear area was affected most. Finally, we examined the two sampling rules in light of the established prognosticators in breast cancer: tumor size, axillary lymph node status, and the Multivariate Prognostic Index (MPI). The two sampling rules resulted in different distributions of morphometric results in the prognostic groups. Our findings emphasize the significance of the sources of variation in nuclear morphometry. They also stress the need for well-standardized morphometric methods in predicting the outcome of breast cancer.

Breast Neoplasms↗
PubMed1989

Patchy basement membrane of rat Leydig cells shown by ultrastructural immunolabeling.

Rat testes were examined by conventional and immunolabeling transmission electron microscopy. Ultrastructurally identifiable continuous basement membranes were found around seminiferous tubules and the interstitial capillaries. Patches of basement membrane were, additionally, found on free surfaces of Leydig cells, between two Leydig cells, and in macrophage-Leydig cell contact sites. The ultrastructural findings were confirmed by immunocytochemical localization of laminin and collagen type IV in the same areas. A close association between the capillary basement membranes and the surfaces of perivascular Leydig cells was also observed. The possible basement membrane-mediated interactions of Leydig cells with other testicular structures, together with the novel bioactive products and regulators of Leydig cells, support the role of these cells as exceptionally complex regulatory centers of testicular functions.

Animals↗
PubMed1989

Rapid Leydig cell proliferation and luteinizing hormone receptor replenishment in the neonatal rat testis after a single injection of human chorionic gonadotropin.

Two-day-old rats were stimulated with a single dose of human chorionic gonadotropin (hCG). Changes in the Leydig cell number, mitotic activity, cell size, and number of luteinizing hormone (LH) receptors were studied. The Leydig cell number of the hCG-treated animals was 1.8 times that of the control on Day 1 and remained elevated for the rest of the 5-day experiment (p less than 0.0001). On Day 1 the number of Leydig cell mitoses in the hCG group was greater (p less than 0.05) than in the controls. The Leydig cell size increased transiently to two times that of the control (p less than 0.01) within the first day after the treatment and returned to control size by Day 5. The number of LH receptors per testis decreased 81% in 1 day (p less than 0.01), but returned to control level by Day 3. Since Leydig cell numbers were constant after Day 1, the rapid receptor recovery was obviously due to restoration of the binding sites rather than increased cell number. The present results demonstrate a rapid proliferative response and rapid LH receptor replenishment in the fetal-neonatal Leydig cells after gonadotropic stimulation. These responses of fetal-type Leydig cells are in clear contrast to those observed in adult testes after a similar stimulation.

Analysis of Variance↗
PubMed1989

Basement membrane and epithelial features of fetal-type Leydig cells in rat and human testis.

The basement membranes of developing Leydig cells in fetal and newborn testis of rat were studied by ultrastructural and immunocytochemical methods. Fetal-type Leydig cells in prenatal rats were organized in irregularly outlined groups in the interstitium and were extensively surrounded by ultrastructurally identifiable basement membranes and immunocytochemically localized laminin and collagen type IV. Prenatal Leydig cell precursors had small patches of laminin and collagen type IV on their surfaces, which indicated that changes in extracellular matrix took place during their differentiation to mature fetal-type Leydig cells. Additionally, ultrastructural evidence was obtained for a basement membrane surrounding the fetal human Leydig cells similar to that in fetal rats. Soon after birth the rat fetal-type cells gathered into distinct clusters surrounded by delicate envelope cells and a discontinuous basement membrane. Basement-membrane structures, laminin, and collagen type IV were observed between the clustered cells as well. The basement membranes covering large cell surface areas of the fetal-type Leydig cells in fetal and newborn rats differed from those of the adult-type cells, which, according to our earlier study, are covered only by small patches of basement membrane. The difference between the basement membranes of the fetal- and adult-type rat Leydig cells further supports the concept of two different Leydig cell populations. The earlier findings of the epithelial nature of the Leydig cells agree with the observation of basement membranes in the Leydig cells.

Animals↗