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M Eskelinen

Publications and source records attributed to M Eskelinen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival.

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.

Adult↗
PubMed1999

Non-suppressed thyrotropin and elevated thyroglobulin are independent predictors of recurrence in differentiated thyroid carcinoma.

OBJECTIVE: Although in most cases differentiated thyroid carcinoma (DTC) responds to surgery and radioiodine (RaI) therapy, some patients will have recurrence and eventually cancer-related death. However, although various prognostic factors of DTC have been identified (e.g. staging, suppressed thyrotropin), none of the previous studies have assessed simultaneously their role in multivariate analysis. DESIGN AND METHODS: In this retrospective population-based study, we reviewed the clinicopathological data of 254 DTC patients treated in eastern Finland during the years 1976-1995, for clinical characteristics, primary treatment, follow-up and cancer recurrence. Tumor stage was based on pathological tumor-node-metastasis (pTNM) classification, and histopathological specimens were re-evaluated. RESULTS: DTC recurrence occurred in 33 patients (13%). In univariate analyses, the predictors of recurrence were older age (>60 years, P<0.05), follicular tumor type (P<0.01), pTNM classification system (P<0.05) and post-ablative radioiodine uptake outside the neck (P<0.05). Non-suppressed serum thyrotropin (TSH) and elevated serum thyroglobulin (>3 microg/l) measured one year after operation were both related to tumor recurrence (P<0.05 and P<0.001 respectively). In multivariate analysis the independent predictors for recurrence were both elevated thyroglobulin (P<0.001) and non-suppressed TSH (P<0.05) independent of histology, pTNM stage and RaI uptake. Adjusted risk ratio for recurrence of DTC for unsuppressed thyrotropin was 2.3, for elevated thyroglobulin 14.0 and, if both conditions were present, the risk ratio increased to 45.1. CONCLUSION: Our results suggest that both non-suppressed serum TSH and elevated serum thyroglobulin are related to an increased risk of DTC recurrence independent of tumor type and pTNM stage.

Adenocarcinoma, Follicular↗
PubMed1998

Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease.

BACKGROUND: Genetic disorders that predispose people to colorectal cancer include the polyposis syndromes and hereditary nonpolyposis colorectal cancer. In contrast to the polyposis syndromes, hereditary nonpolyposis colorectal cancer lacks distinctive clinical features. However, a germ-line mutation of DNA mismatch-repair genes is a characteristic molecular feature of the disease. Since clinical screening of carriers of such mutations can help prevent cancer, it is important to devise strategies applicable to molecular screening for this disease. METHODS: We prospectively screened tumor specimens obtained from 509 consecutive patients with colorectal adenocarcinomas for DNA replication errors, which are characteristic of hereditary colorectal cancers. These replication errors were detected through microsatellite-marker analyses of tumor DNA. DNA from normal tissue from the patients with replication errors was screened for germ-line mutations of the mismatch-repair genes MLH1 and MSH2. RESULTS: Among the 509 patients, 63 (12 percent) had replication errors. Specimens of normal tissue from 10 of these 63 patients had a germ-line mutation of MLH1 or MSH2. Of these 10 patients (2 percent of the 509 patients), 9 had a first-degree relative with endometrial or colorectal cancer, 7 were under 50 years of age, and 4 had had colorectal or endometrial cancer previously. CONCLUSIONS: In this series of patients with colorectal cancer in Finland, at least 2 percent had hereditary nonpolyposis colorectal cancer. We recommend testing for replication errors in all patients with colorectal cancer who meet one or more of the following criteria: a family history of colorectal or endometrial cancer, an age of less than 50 years, and a history of multiple colorectal or endometrial cancers. Patients found to have replication errors should undergo further analysis for germ-line mutations in DNA mismatch-repair genes.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer.

Hyaluronan (HA) is a linear high molecular weight extracellular polysaccharide. It is thought to be involved in mitosis and the enhancement of wound healing, tumor invasion, and metastasis. Because its clinical relevance in cancer has not been explored, we scored HA in colorectal adenocarcinoma and studied its relationship with patient survival. A specific probe prepared from cartilage proteoglycan aggregates was used to stain paraffin-embedded tumor samples from 202 colorectal adenocarcinoma patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the percentage of HA-positive carcinoma cells (HA%) and HA intensity in cancer cells correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. Ninety-three % of tumors had at least a proportion of carcinoma cells positive for HA. HA intensity in tumor epithelium was stronger in Dukes' stages C and D tumors and in high-grade tumors. The cancer-related survival rate was lower among patients with strong HA intensity in tumor epithelium (P < 0.001) and high HA% (P < 0.001). Recurrence-free survival was also shorter in patients with an intense signal for HA (P = 0.001) and high HA% in tumor epithelium (P = 0.04). HA intensity in tumor epithelium independently predicted survival and recurrence-free survival (Cox's analysis). We conclude that a high proportion of HA-positive cancer cells and high intensity of the HA-signal predicts a poor survival rate. The abnormal expression of HA in the neoplastic colon epithelial cells is suggested to provide a distinct advantage for invasive growth and metastasis.

Adenocarcinoma↗
PubMed1998

Expression of CD44 standard and variant-v6 proteins in transitional cell bladder tumours and their relation to prognosis during a long-term follow-up.

The expression of the standard CD44 (CD44s) and its v6 isoform (CD44v6) was analysed immunohistochemically in 173 cases of transitional cell bladder cancer. The results of immunohistochemical analyses were related to established prognostic factors and clinical follow-up data. The expression intensity of CD44s in non-basal tumour cells was significantly related to TN classification, S-phase fraction (SPF), mitotic index, grade, density of tumour infiltrating lymphocytes. The expression intensity of CD44v6 in non-basal tumour cells was inversely related to DNA ploidy, SPF, and mitotic index. The expression intensity of CD44v6 in basal tumour cells was also inversely related to T-category, grade, papillary status, DNA ploidy, SPF, and mitotic index. Strong expression of CD44s in non-basal tumour cells was related to unfavourable outcome in univariate analysis (p = 0.008), whereas the strong expression of CD44v6 in both non-basal cells (p = 0.005) and basal cells (p = 0.0008) was related to high survival probability. In multivariate survival analysis, the expression intensity of CD44v6 was independently related to favourable outcome in muscle invasive tumours, while in superficial tumours, CD44s was an independent prognostic factor. The results suggest that the expression of CD44s and CD44v6 is associated with malignant features and prognosis in bladder cancer.

Adult↗
PubMed1998

Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer.

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I-II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I-II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value.

Adult↗
PubMed1998

Treatment of missing data values in a neural network based decision support system for acute abdominal pain.

In this study different substitution methods for the replacement of missing data values were inspected for the use of these cases in a neural network based decision support system for acute appendicitis. The leucocyte count had the greatest number of missing values and was used in the analyses. Four different methods were compared: substituting means, random values, nearest neighbour and a neural network. There were great differences in the substituted leucocyte count values between different methods and only nearest neighbour and neural network agreed about most of the cases. The importance of the substitution method for the final diagnostic classification of the patients by the neural network based decision support system was found to be small.

Abdominal Pain↗
PubMed1998

Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value.

OBJECTIVES: p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell at the G1 phase by inhibiting DNA replication through interaction with proliferating cell nuclear antigen (PCNA). Experimental analyses of human bladder cancer cell lines show that p21 might be considered a tumour suppressor gene since it is able to induce apoptosis like p53. The prognostic value and expression of p21(waf1/cip1) is incompletely studied in bladder cancer at present. METHODS: The expression of p21 protein was immunohistochemically analysed in paraffin-embedded specimens of 186 patients with primary transitional cell bladder tumours. The results of immunohistochemical analysis were related to known prognostic factors and complete long clinical follow-up data (over 11 years). RESULTS: The expression of p21(waf1/cip1) protein was significantly related to DNA ploidy, S phase fraction, mitotic index, apoptotic index, morphometric nuclear factors, and the expression of p53 and PCNA proteins, whereas it was unrelated to grade or TNM classification. In univariate survival analysis, the expression of p21(waf1/cip1) protein was not significantly related to prognosis. Independent prognostic factors were T category, papillary status and mitotic index. CONCLUSION: The results indicate that although the expression of p21(waf1/cip1) protein is related to indicators of cell proliferation, apoptosis and p53 expression, it has no better prognostic value than already established prognostic factors in bladder cancer.

Adult↗
PubMed1998

Usefulness of history-taking, physical examination and diagnostic scoring in acute renal colic.

OBJECTIVE: The accuracy of the clinical diagnosis of acute renal colic was studied in connection with the survey of acute abdominal pain by the Research Committee of the World Organization of Gastroenterology. The diagnostic efficiency of various clinical symptoms, signs and tests have not previously been analyzed in the diagnosis of acute renal colic, and therefore the study is of potential importance. METHODS: 1,333 patients presenting with acute abdominal pain were included in the study. The clinical findings in each patient were recorded in detail, using a predefined structured data collection sheet, and the collected data were compared with the final diagnoses of the patients. Twenty-three clinical history variables, 14 clinical signs and 3 tests were evaluated in a single variable and multivariate analysis. RESULTS: In multivariate logistic regression analysis, the most significant predictors of acute renal colic were urine, tenderness, renal tenderness, duration of pain and appetite. The sensitivity in detecting acute renal colic was 0.84, with a specificity of 0.99 and an efficiency of 0.98. To sum up the contributions of most significant diagnostic factors, a diagnostic score (DS) was built. This score incorporated independent variables, e.g. urine, tenderness, renal tenderness, duration of pain, appetite and sex. The DS reached a sensitivity of 0.89 in detecting acute renal colic, with a specificity of 0.99 and an efficiency of 0.99. CONCLUSIONS: The results clearly show that acute abdominal pain with normal appetite, short duration of pain (</=12 h), loin or renal tenderness and hematuria (erythrocytes >10) are indicative of acute renal colic, and therefore, in this particular clinical question, careful history-taking and physical examination are of utmost importance. In our study, the DS system performed well considering the simple nature of its structure. However, to minimize the risk to the patient, we recommend that the DS is used only as an aid in decision-making when there is uncertainty as to the diagnosis of acute renal colic and the need for immediate treatment. In addition, the possibility of obstructive pyelonephritis in combination with renal colic should be considered clinically.

Acute Disease↗
PubMed1998

Diagnosis of acute appendicitis in two databases. Evaluation of different neighborhoods with an LVQ neural network.

The use of an artificial neural network system was studied in the diagnosis of acute abdominal pain, especially acute appendicitis, with patients from Finland and Germany. Separate Learning Vector Quantization (LVQ) neural networks were trained with a training set from each database and also with a combined database. Each neural network was evaluated separately with a test set of cases from each database. With the combined database different neighborhood methods were compared to find the optimal choice for this decision-making problem. The acute appendicitis cases of the Finnish test data set were classified well with all the networks, but the cases of the German test set were difficult to classify for the Finnish network. The use of larger neighborhoods increased the sensitivity of the classification by nearly 10%. The differences in the results of the Finnish and German databases suggest that there are differences in the data collection or patient populations between centers. Therefore, care must be taken when using decision-support systems which have been developed in other centers. Neural networks offer a method to evaluate differences between databases. With the use of larger neighborhoods, the effects of the differences on the accuracy of the classification can be partly diminished.

Abdominal Pain↗
PubMed1997

Nuclear morphometry as a predictor of disease outcome in gastric cancer.

Nuclear morphometric features including nuclear area (NA), nuclear perimeter (PE), their variation (SDNA, SDPE), and mean largest and smallest nuclear diameters (Dmax, Dmin) were examined in 116 patients with stage I-II gastric adenocarcinoma. Morphometric measurements were compared with tumour differentiation, depth of invasion (pT), lymph node status (pN), and Lauren classification. All morphonuclear features were significantly larger in the intestinal type than in the diffuse type of cancer. None of the morphometric variables was related to TNM status or tumour size. Nuclear area and perimeter and their variation were closely related to survival in univariate analysis, patients with small and regular nuclei surviving longer. In the multivariate analysis, pT, pN, perineural invasion, and the standard deviation of nuclear perimeter (SDPE) were independent predictors of survival. Nuclear morphometry is a quantitative, objective, and highly reproducible method of revealing malignant features in several neoplasms. The results of the present study suggest that nuclear morphometric data may help in defining prognosis in gastric cancer.

Adenocarcinoma↗
PubMed1997

Development of T-tube tracts in piglets: effect of insertion method and material of T-tubes.

T-tube-related bile leakage is a considerable problem in liver transplantation but rather rare in surgery of biliary lithiasis. To investigate the effect of T-tube insertion method and material on the intraperitoneal T-tube tract, we performed a choledochotomy and insertion of T-tube (four of silicone, seven of latex, four of silicone with a latex sheath around the long arm) for 2 weeks on 15 piglets (choledochotomy group), and sutured a transected bile duct over a T-tube stent in nine piglets (five silicone, four latex), inserted similarly as in liver transplantations, for 6 weeks. Sixteen patients underwent cholectochotomy and T-tube drainage with a latex T-tube (n = 8) and latex-sheathed silicone T-tube (n = 8) for a median 9 (7-21) days. Histological examination of T-tube tracts in piglets was made, and complications after T-tube removal in the latex T-tube group were compared with those in the latex-sheathed silicone T-tube group. In piglets, latex T-tubes induced better tracts than silicone T-tubes (P < 0.05). Piglets in the choledochotomy group had tracts superior to those in the anastomotic stent group (P < 0.05). There was one bile leakage in the latex T-tube group, and none in the latex-sheathed silicone T-tube group. We conclude that T-tube tract development is affected by both the material and the insertion method of T-tubes. A silicone T-tube with a latex sheath around the long arm may also be a good choice for T-tube material in liver transplantation.

Adult↗
PubMed1997

Prognostic value of Ki-67 expression in renal cell carcinomas.

OBJECTIVE: The aim of the study was to determine the prognostic power of Ki-67 immunostaining in renal cell carcinomas (RCC). METHODS: Clinical follow-up data were reviewed in 111 RCC and the results of Ki-67 immunolabelling were correlated to standard prognostic factors and survival data of the patients. RESULTS: Ki-67 expression correlated with tumor grade (p < 0.0001) and mitotic activity (p < 0.0001). In survival analysis Ki-67 expression could be used to divide patients into different prognostic groups (p = 0.0003). In separate analysis with M0 tumors Ki-67 immunolabelling was a powerful predictor of survival (p = 0.0016) as well as disease-free survival (DFS; p = 0.0067). In T1-2N0M0 tumors Ki-67 immunolabelling was superior (p = 0.0005) to other prognostic factors in survival analysis as well as in predicting DFS (p = 0.0006). Grade-2 tumors could be separated into distinct prognostic groups according to Ki-67 labelling (p = 0.0098). In Cox's multivariate analysis Ki-67 was an independent prognostic factor in all three subgroups of RCC. CONCLUSIONS: The results show that Ki-67 expression is an independent prognostic factor in renal adenocarcinoma and could be applied in defining proper therapy for patients suffering from this malignancy.

Adult↗
PubMed1997

Value of Ki-67 immunolabelling as a prognostic factor in prostate cancer.

OBJECTIVE(S): The aim of the study was to analyze the results of Ki-67 immunostaining in prostatic adenocarcinoma and to assess its prognostic value. METHODS: Clinical follow-up data was reviewed in 190 prostatic adenocarcinomas and the results of Ki-67 immunolabelling were correlated to standard prognostic factors and survival data of the patients. All stage and grade categories were included. RESULTS: Ki-67 expression correlated significantly with histological differentiation of tumors, indicators of cell proliferation, perineural growth, density of tumor-infiltrating lymphocytes and TM classification. In survival analysis, Ki-67 expression was able to discriminate patients into different prognostic groups (p = 0.0035). In a separate analysis including T1-2M0 tumors, Ki-67 immunolabelling was a significant predictor of survival (p = 0.0258). In Cox's multivariate analysis Ki-67 was an independent prognostic factor in the entire cohort. CONCLUSIONS: The results show that Ki-67 expression is a potentially useful prognostic factor in prostatic adenocarcinoma and it could be used as an additional criterion in defining a correct prognostic category in this malignancy.

Adenocarcinoma↗
PubMed1996

Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing.

DNA methylation has been studied intensively during the past years in order to elucidate its role in the regulation of gene expression, gene imprinting and cancer progression. Earlier studies have shown that a general genomic under-methylation is associated with chronic lymphocytic leukemia and metastatic prostate cancer. Site-specific methylation changes, as revealed by the use of methylation-sensitive restriction enzymes, have been reported to occur in the promotor region of the calcitonin gene in chronic myeloid leukemia as it progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid neoplasms and in non-lymphocytic leukemia. We have now explored possible methylation changes associated with benign and malignant breast tumors. Two approaches were employed: (i) chemical determination of general genomic methylation status and (ii) base-specific analysis of the methylation changes in the promoter of the calcitonin gene with the aid of genomic sequencing. The results did not reveal any changes of total DNA 5-methylcytosine content in ductal carcinoma of breast in comparison with benign tumors. There was a small, yet significant, increase in 5-methylcytosine content in lobular carcinoma. Genomic sequencing of the promoter region of the calcitonin gene, however, revealed a striking hypermethylation at or around the transcription start site of the gene in ductal carcinomas. In benign tumors and lobular carcinomas, this region was either entirely unmethylated or only slightly methylated. The latter changes may reflect a regional hypermethylation of the short arm of chromosome 11, which harbors, in addition to the calcitonin gene, a number of putative or established tumor-suppressor genes. Our results demonstrate that genomic sequencing in its present form can be used for a reliable and precise DNA methylation analysis of primary human tumors.

5-Methylcytosine↗
PubMed1996

Body-size indicators and risk of breast cancer according to menopause and estrogen-receptor status.

Associations between the risk of breast cancer and body-size indicators at the time of breast-cancer diagnosis were assessed among 328 pre-menopausal or post-menopausal cases and 417 controls participating in the Kuopio Breast Cancer Study. This case-control study follows the protocol of the international Collaborative Study of Breast and Colorectal Cancer. When the potential confounding factors were taken into account, tallness was related to increased risk of breast cancer, especially in post-menopausal women, whereas no clear association with body-mass index (BMI) was found. Waist-to-hip ratio (WHR) was the most important risk factor in both pre-menopausal and post-menopausal women. The post-menopausal cases with high positive estrogen-receptor status (ER++) had the highest weight and BMI; they had also the biggest weight gain since the age of 20. However, the association between WHR and breast cancer appeared to be independent of estrogen-receptor status. Our results suggest that WHR may be a better marker for breast cancer than the degree of adiposity.

Adult↗
PubMed1996

Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland).

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n = 34) and with breast cancer (n = 32). In postmenopausal women, lower dietary intake (P = 0.006) and a smaller concentration of vitamin E in breast adipose tissue (P = 0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r = 0.25, P = 0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.

Adipose Tissue↗