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S Toikkanen

Publications and source records attributed to S Toikkanen.

At least 37 records · Page 2Linked to original sources

DNA aneuploidy in ectopic pregnancy and spontaneous abortions.

The nuclear DNA content of 55 ectopic tubal pregnancies was studied by flow cytometry from paraffin embedded tissue blocks. An abnormal amount of DNA content was found in 24% of the cases. This was a significantly higher percentage than encountered in 92 spontaneous abortions studied by the same method in the same population (8%, P = 0.01). The result indicates that, in addition to the maternal factors, abnormal embryogenesis with grave chromosomal aberrations may play a major role in the etiology of ectopic pregnancy.

Abortion, Spontaneous↗

Prostatic dysplasia associated with increased expression of c-myc in neonatally estrogenized mice.

Neonatal estrogenization of the mouse with diethylstilbestrol (DES; 2 micrograms./pup/day for days 1 to 3) or 17 beta-estradiol (200 micrograms./pup/day for days 1 to 3) resulted in epithelial dysplasia in the posterior periurethral region of the prostate at the age of 1 year. The dysplastic lesions ranged from mild to severe and, in addition to emergence of nuclear anaplasia, the architectural pattern of the glands was disturbed. Prenatal estrogenization (100 micrograms./kg. of maternal body weight on days 13 and 15 of gestation) only resulted in mild epithelial hyperplasia and occasional dysplasia in the ventral lobe of the prostate, but not in the posterior periurethral region. When neonatally estrogenized mice were allowed to grow until the age of 18 months, the degree and extent of the dysplasia of the posterior periurethral region was increased, but no frank invasion or metastases could be demonstrated. Combined estrogen and androgen treatment of neonatally estrogenized mice for 3 months (between 9 and 12 months of age) augmented nuclear dysplasia, but no invasive growth was seen in this group, either. Mild epithelial dysplasia was found in the dorsolateral lobes and coagulating glands of similarly treated control animals. A relation between the activation of certain proto-oncogenes and the development of several cancers has been shown in humans and experimental animals. In the present study, Northern blot analysis of total RNAs showed that the levels of c-myc mRNA were increased in the ventral and dorsolateral lobes, coagulating glands and prostatic urethra of neoDES mice at the age of 9 months. However, it remains to be determined whether the increase in c-myc expression is involved in the development of hyperplastic and dysplastic changes in the prostate of neoDES mice.

Animals↗

Does the month of diagnosis affect survival of cancer patients?

Some earlier studies based on relatively small data sets have suggested that the month of diagnosis affects survival of breast cancer patients. This phenomenon has been suggested to be attributable to daylight-related hormonal factors. Factors related to the holidays of both the medical personnel and the women themselves might also provide the explanation. In this study we assessed the effect of the month of diagnosis on the survival of 32,807 female breast cancer patients diagnosed in Finland in 1956-1985. Our results indicate that the month of diagnosis is a significant prognostic factor after adjusting for age at diagnosis, period of diagnosis, and stage at diagnosis. The adjusted relative excess risk of death was highest among those diagnosed in July and August, and lowest in March and November, the difference between the lowest and highest risk being 18%. Since colorectal cancer should not have any daylight-related hormone dependent risk determinants, a control cohort of 12,950 women with a diagnosis of colorectal cancer in the same calendar period was studied in a similar way. The survival pattern by month of diagnosis among the colorectal cancer patients was similar to that among breast cancer patients, indicating that general factors associated with the health behaviour of women and the health services (such as holidays) rather than biological factors may cause seasonal variations in survival of cancer patients.

Breast Neoplasms↗

Glycoprotein CD44 expression and its association with survival in breast cancer.

To investigate the clinical significance of CD44 expression (lymphocyte-homing receptor) in adenocarcinoma, deparaffinized sections from 198 female breast carcinomas were stained with Hermes-3 MoAb for CD44 glycoprotein. In 16% of the cancers most (> or = 90%) of the cancer cells stained positively for CD44, whereas the rest of the cancers were either heterogenous (46%) or negative (38%) in CD44 staining. Cancers with > 50% CD44 positive cells were more often poorly differentiated (grade 3) than those with < or = 50% positive cells (38 vs. 19%, P = 0.006), they had higher mitotic counts (P = 0.04), and were more often estrogen receptor negative (52 vs. 31%, P = 0.01). Among ductal not otherwise specified cancers and node-positive cancers strong CD44 expression was associated with poor outcome (P = 0.05 and 0.02, respectively). However, CD44 expression was not an independent prognostic factor in these subgroups in a multivariate analysis. Unlike in lymphomas the unfavorable prognosis associated with CD44 expression may not be explained by the greater metastatic potential of CD44-positive cells, because the difference in mortality between the groups appeared to diminish with time, and CD44 positivity was associated with aggressive histological features.

Adenocarcinoma↗

Effect of DNA ploidy classification on prognosis in breast cancer.

A series of 327 breast cancers was analyzed for DNA ploidy by flow cytometry from paraffin-embedded tissue, and the resulting DNA histograms were classified independently by 6 researchers in the field as DNA diploid (Di), aneuploid (An), tetraploid (Te), multiploid (Mu), or technically uninterpretable. The frequency of diploid, aneuploid, tetraploid and multiploid cancers varied from 28 to 41%, 33 to 49%, 8 to 21% and 2 to 6%. According to the scale Di-An-Te-Mu, DNA ploidy was not significantly associated with breast-cancer mortality by 2 classifiers, but if DNA euploid cancers (Di+Te) were tested against non-euploid, or diploid cancers against non-diploid, all classifiers found DNA euploid and diploid cancers to have better prognosis. Mortality associated with diploid or tetraploid cancers decreased with improving histogram quality and increasing uniformity of classification, whereas that associated with aneuploid cancers remained unaltered. Among the cases where all classifiers agreed on ploidy, tetraploid, diploid and aneuploid cancers were associated with 100%, 88% and 68% 5-year survival rates. In this sub-set the S-phase fraction and possibly DNA ploidy were independent prognostic factors, together with histological grade, axillary node status, and primary tumor size.

Breast Neoplasms↗

Aggressiveness of breast cancers found with and without screening.

OBJECTIVE: To examine how breast cancers found by mammographic screening differ from those found outside screening. DESIGN: Comparative cohort study. SETTING: Turku, southwestern Finland. PATIENTS: 126 women aged 40-74 years with breast cancer detected during the first round of mammographic screening in 1987-90 and 125 women within the same age range with breast cancer detected outside screening during the same period. MAIN OUTCOME MEASURES: Primary tumour size, axillary nodal status, histological features, oestrogen and progesterone receptor concentrations, ploidy, and S phase fraction. RESULTS: Compared with the controls women with cancers detected by screening had a smaller primary tumour (57 (46%) screened v 11 (10%) controls had tumours less than or equal to 11 mm in diameter, p less than 0.0001), and less often had axillary nodal metastases (104 (83%) screened v 71 (57%) controls node negative, p less than 0.0001). After adjustment for the smaller size of the primary tumour compared with control cancers, those cancers detected by screening were less likely to have axillary nodal metastases (odds ratio 0.44, 95% confidence interval 0.23 to 0.84), poor histological differentiation (0.20, 0.08 to 0.49), high mitotic counts (0.38, 0.15 to 0.97), tumour necrosis (0.45, 0.22 to 0.93) or to be of the ductal histological type (0.46, 0.22 to 0.95). They had low oestrogen receptor (0.29, 0.12 to 0.70) and progesterone receptor (0.35, 0.17 to 0.92) concentrations less often and had smaller S phase fractions (0.72, 0.55 to 0.96) than control cancers. CONCLUSIONS: Even after adjustment for the smaller size of screen detected breast cancers, their histological and cytometric features suggest low malignant potential. They may also be less likely to metastasise to axillary lymph nodes than cancers found outside screening.

Adult↗

Correlations of liver echo intensity with cytology and chemical measurements of fat, water and protein content in live burbots (Lota lota).

Six live burbot fish (Lota lota) were examined on the 1st, 7th and 15th day after capture. The echo intensity of the liver tissue was correlated with chemically measured fat and water content and with the tissue cytology. At the end of the study, the collagen and total protein contents of the livers were also measured. The increasing size of fat droplets and clustering of droplets correlated well with the echo intensity (p = 0.0012), but there was no statistically significant correlation between echo intensity and chemically measured fat concentration (p = 0.1989). These results indicate that the echogenicity is a function of the liver histomorphology. No significant correlation was found between the echo intensity and liver collagen, total protein content, or amounts of water. The burbots tolerated transport and repeated anesthesia and appear well suited for experimental ultrasound studies.

Animals↗

Wolman disease: morphological, clinical and genetic studies on the first Scandinavian cases.

On the Aland Islands, a 1-month-old girl was diagnosed as having Wolman disease. The diagnosis was confirmed neurochemically; a decreased activity of acid lipase was noted in the proband and her parents had typical carrier values. This is the first Scandinavian case reported. The skin biopsy revealed cytoplasmic accumulations identical to those noted in two sibs who highly probably had Wolman disease during the 1950s. Both these sibs died at the age of about 3 months and presented a heavy accumulation of lipid material in lymph nodes, spleen, adrenal glands, liver, gut, and also some pathological alterations in other organs. Electron microscopic findings from deparaffinized samples showed cytoplasmic accumulation of lipid material similar to that noted in Wolman disease. Genealogical analyses revealed that the index families had ancestors from the same restricted area and also common ancestors during the 17th century. The parents of the two affected sibs were born on a small island and were related in many different ways. On the basis of genealogical studies and other genetic investigations performed, the importance of founder and drift effect for manifestations of rare hereditary disorder in isolates is stressed.

Consanguinity↗

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.

Antigens, CD↗

Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up.

PURPOSE: To study retrospectively the long-term prognostic significance of HER-2 oncoprotein expression in breast cancer (BC). PATIENTS AND METHODS: Two hundred nine consecutive female patients with invasive operable BC from a defined urban population were observed for a median of 30 years. Tissue expression of HER-2 oncoprotein was demonstrated by using an immunoperoxidase procedure. RESULTS: Fifty-five (26%) patients had cancer and a positive HER-2 oncoprotein stain reaction. They had significantly worse 10- and 25-year survival rates than those patients who had a negative stain reaction in their cancer (31% v 48% and 31% v 39%, respectively; P = .004). HER-2 expression was also associated with a poorer survival among patients who had axillary nodal metastases (P = .003; n = 104), but not among those patients who did not have metastases. HER-2 expression was related to the ductal histologic type, poor histologic grade, and high mitotic count, but not to tumor size, axillary nodal status, DNA ploidy, or S-phase fraction (SPF). In a multivariate analysis among patients with nodal metastases, HER-2 expression was an independent prognostic factor (P = .04) that predicted poor survival. However, if the entire series was entered onto the analysis, it did not emerge as an independent factor. CONCLUSIONS: HER-2 oncoprotein expression has long-term prognostic significance for predicting poor survival in BC, and it has an independent prognostic value among patients who presented with axillary nodal metastases. This result is contradictory to the argument that HER-2 expression is only a marker for drug resistance because the patients were not given adjuvant drug therapy.

Adult↗

Risk factors for screen-detected breast cancer. A case-control study.

Risk factors for breast cancer (BC) detected in mammography screening were sought using a questionnaire among 31,927 women aged from 40 to 74 years who attended screening. Data from 204 women with screen-detected BC were compared with those of 612 controls who did not have BC in screening. Mothers of women with BC had more often BC than those of the controls (8% vs. 3%, odds ratio, OR, 3.18, 95% CI 1.59-6.35). Women with screen-detected BC were older at their first childbirth (25.7 years vs. 24.7 years, OR 1.61, 1.14-2.33), and younger at menarche (13.6 years vs. 13.8 years, OR 1.38, 1.00-1.91), but there was no significant difference in the body mass index, number of pregnancies, breast size, smoking, or in the use of contraceptive pills between the cases and the controls. In multivariate logistic regression analyses, late age at the first childbirth, BC in the mother, and early age at menarche were independent risk factors for screen-detected BC but they appear to be of limited value in targeting screening in the female population aged from 40 to 74 in order to improve its cost-effectiveness.

Adult↗

Identification of subgroups with favorable prognosis in breast cancer.

The prognostic significance of 16 factors was investigated in a series of 311 women with unilateral, invasive breast carcinoma without distant metastases (M0) and treated with mastectomy. The series consisted of 93% of such cases diagnosed histologically in the city of Turku, Finland, from 1980 to 1984. Mitotic count, histological and nuclear grades, extent of tumor necrosis, axillary nodal status (pN), tumor size (pT), estrogen and progesterone receptor (PR) contents, and S-phase fraction were the most powerful single factors (p = 0.0001 or less). Axillary node negative cancers with no or only spotty tumor necrosis (92% of all pN0 cases) were associated with a 96% 5-year survival rate corrected for intercurrent causes. Among the axillary node positive cases the combination of high PR content (greater than 60 fmol/mg protein) and a low mitotic count could identify a subgroup with a 96% 5-year corrected survival rate (25% of all pN+ cases). It is concluded that both pN0 and pN+ breast cancer contain identifiable subgroups with greatly different prognosis.

Breast Neoplasms↗

Comparison of breast carcinomas diagnosed in the 1980s with those diagnosed in the 1940s to 1960s.

OBJECTIVE: To find out if breast carcinomas diagnosed in the 1980s differ from those diagnosed a few decades ago. DESIGN: Retrospective comparative cohort study. SETTING: City of Turku, south western Finland. PATIENTS: 439 patients with breast carcinoma diagnosed in 1945-65 with a median follow up of 27 years (95% of all those histologically diagnosed in Turku); and 370 patients with breast carcinoma diagnosed in 1980-4 with a median follow up of 6 years (94% of all those histologically diagnosed in Turku). MAIN OUTCOME MEASURES: Breast cancer incidence, mortality from breast cancer, age at diagnosis, stage of cancer, seven histological factors, DNA ploidy. RESULTS: Age adjusted incidence of breast cancer increased from 30.8/100,000 person years in 1953-7 to 62.2/100,000 in 1983-7; mortality in breast cancer increased from 16.7 to 17.2/100,000 person years. Survival of patients with stages II to IV (but not with stage I) improved. The mean age at diagnosis increased from 55.5 years in 1945-55 to 62.5 years in 1980-4 (p less than 0.0001); the proportion of patients with T0-1 carcinomas increased from 13% to 41% (p less than 0.0001) and with pN0 carcinomas from 43% to 55% (p = 0.003) from 1945-65 to 1980-4. There was no change in histological type or DNA ploidy of breast cancer, but in the 1980-4 cohort carcinomas were more often well differentiated, had lower mitotic counts and less nuclear pleomorphism, more often had a well defined tumour margin, and had less tumour necrosis. There was, however, no difference between the two cohorts in these histological characteristics except for tumour necrosis when they were compared in a multivariate log linear model at a given size of primary tumour. CONCLUSION: Improved survival with breast cancer can at least partially be explained by detection of increased numbers of small carcinomas with favourable histological characteristics.

Adult↗

Glycogen-rich clear-cell carcinoma of the breast: a clinicopathologic and flow cytometric study.

Six glycogen-rich clear-cell carcinomas (GCC) were found among 439 cases of breast cancer (BC) in a thorough search among a defined urban population. Five of these six patients had axillary lymph node metastases at diagnosis and all five died from their breast cancer within 7 years following the diagnosis. Tumors with histologic features of GCC were larger (P = 0.03), and they had a large DNA index (greater than 1.3) in flow cytometric DNA analysis more frequently than BCs in general (P = 0.04). All GCCs were nondiploid and had a high S-phase fraction (greater than 9%, mean 19.2%), which suggests that BCs with glycogen-rich cell features may be more aggressive than BCs in general.

Adenocarcinoma↗

Histological features, DNA content and prognosis of breast carcinoma found incidentally or in screening.

Histology features, the nuclear DNA content and prognosis of 42 female breast carcinomas found in a physical examination based screening, 54 breast cancers found incidentally by medical personnel, and 274 breast cancers first suspected by the patient were compared. There was no significant difference in the distribution by primary tumour size (P = 0.08) or histological type (P = 0.87) of breast cancer between the screen-detected and 139 self-suspected cancers of women with similar mean age and living at the same time in the same city, but the screen-detected carcinomas were better differentiated (P = 0.0002), and had less mitoses (P = 0.008), less tumour necrosis (P = 0.004) and DNA aneuploidy (P = 0.01), smaller S-phase fractions (P = 0.009), less axillary metastases (P = 0.04), and had better outcome (P = 0.005) than self-suspected carcinomas. These parameters did not differ significantly between the screen-detected and incidentally found cancers, but incidental cancers had more often axillary metastases (P = 0.02). The results indicate that screen-detected breast carcinomas have favourable biological features suggesting low degree of malignant potential.

Breast Neoplasms↗

Association between the month of diagnosis and prognosis in breast carcinoma.

The effect of the month of diagnosis on survival was investigated in two series of unilateral invasive breast cancer, of which one comprised 95% of all such histologically diagnosed breast carcinomas in the city of Turku, Finland, in 1945 to 1965 (n = 401), and the other 94% of all such carcinomas diagnosed in 1980 to 1984 (n = 337). If the histological diagnosis was made in January, February, or August to October in 1945-65, or in July to September in 1980-84, mortality in breast cancer was greater than if the diagnosis was made during the rest of the year (P = 0.03 and 0.009, respectively). Cancers diagnosed during the unfavourable months had more tumour necrosis in both series, and higher mitotic count and larger tumour size in the 1945-65 series. The number of diagnosed cases was usually less than the median during the months associated with unfavourable prognosis. Hypotheses to explain the altering prognosis by the month of diagnosis include seasonal hormonal changes and social factors.

Breast Neoplasms↗

Determination of fat content of burbot (Lota lota) liver with low field MR imaging (0.04 T).

A reconstructed separate fat image was used for studying the fat content of the liver of 12 dead and six living fasting burbots (Lota lota) in a 0.04 T magnetic field with olive oil as a reference. The correlation between the MR intensities and the results of the cytological, histological and chemical fat measurements, as well as chemically measured water, collagen and total protein contents were examined. The MR signal intensity in reconstructed fat images correlated well with the changes in fat content of the liver in living fish (r = 0.69, P = 0.0014). Also the contents of water (r = -0.66, P = 0.003) and total protein (r = -0.91, P = 0.013) correlated significantly with the MR signal intensity. The reconstructed fat image is thus a reliable method for following the changes in tissue fat content. The living burbot is an applicable test animal for studying the hepatic fat content with MR.

Animals↗