Biomedical subjects

M Eskelinen

Publications and source records attributed to M Eskelinen.

At least 19 recordsLinked to original sources

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↗

PubMed1996

The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer.

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P < 0.0001), the volume-corrected mitotic index (P < 0.0001), histological grade (P < 0.0001), the apoptotic index (P < 0.0001), oestrogen and progesterose receptor content (P < 0.0001 for both) and p53 accumulation (P = 0.001). No correlation was found between Ki-67 expression and lymph node status (P = 0.25), metastasis at operation (n = 0.81) or tumour size (n = 0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P = 0.001) and in axillary-lymph-node-negative (ANN) patients (P = 0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P = 0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P = 0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.

Breast Neoplasms↗

PubMed1996

Comparison of different neural network algorithms in the diagnosis of acute appendicitis.

Four different neural network algorithms, binary adaptive resonance theory (ART1), self-organizing map, learning vector quantization and back-propagation, were compared in the diagnosis of acute appendicitis with different parameter groups. The results show that supervised learning algorithms learning vector quantization and back-propagation were better than unsupervised algorithms in this medical decision making problem. The best results were obtained with the learning vector quantization. The self-organizing map algorithm showed good specificity, but this was in conjunction with lower sensitivity. The best parameter group was found to be the clinical signs. It seems beneficial to design a decision support system which uses these methods in the decision making process.

Adolescent↗

PubMed1996

Expression of the apoptosis suppressing bcl-2 protein in transitional cell bladder tumours.

The expression of bcl-2 protein was studied by immunohistochemistry using a monoclonal antibody in 158 cases of transitional cell bladder tumours. The bcl-2 protein was expressed in basal cells in normal transitional epithelium and 68% of the transitional cell tumours showed bcl-2 positivity in the basal cells. The expression of bcl-2 in basal cells was positively correlated to over-expression of epidermal growth factor receptor in tumour cells. The expression of bcl-2 in non-basal cells was weak in 20% and strong in an additional 13% of tumours. The expression of bcl-2 in non-basal cells was positively correlated to T-category, M-category, grade, papillary status, DNA ploidy, S phase fraction, mitotic index, nuclear area and over-expression of epidermal growth factor receptor. Recurrence-free interval of Ta-T1 tumours was related to bcl-2 positivity in non-basal cells. Tumours with bcl-2 positive non-basal cells had an unfavourable prognosis but, in multivariate analysis, expression of bcl-2 had no independent prognostic value.

Adult↗

PubMed1995

Apoptosis suppressing protein bcl-2 is expressed in well-differentiated breast carcinomas with favourable prognosis.

The expression of bcl-2 protein was analysed immunohistochemically in 202 female breast carcinomas. The intensity of bcl-2 expression was inversely related to tumour grade (P < 0.0001), tumor necrosis (P < 0.0001), mitotic index (P < 0.0001), oestrogen receptor content (P < 0.0001), progesterone receptor content (P = 0.0007), S-phase fraction (P = 0.00047), and apoptotic index (P = 0.087). A high fraction of bcl-2-positive cells was related to ductal or lobular type (P = 0.03) and slight nuclear pleomorphism (P = 0.03). Heterogeneous expression of bcl-2 protein was associated with high grade (P = 0.02), severe nuclear pleomorphism (P = 0.02), DNA aneuploidy (P = 0.018), high S-phase fraction (P = 0.05), and early metastasis (P = 0.03). Intense expression of bcl-2 protein was significantly related to favourable outcome in the entire cohort (P = 0.0013), as well as in axillary lymph node-negative (ANN) tumours (P = 0.0124). Long recurrence-free periods in the entire cohort (P = 0.037) and in ANN tumours (P = 0.08) were confined to cases with intense expression of bcl-2 protein. In multivariate analysis, bcl-2 expression had no independent prognostic value in the entire cohort or in axillary lymph node-negative breast carcinomas, whereas it was a weak independent prognostic factor in axillary lymph node-positive breast carcinomas.

Adult↗

PubMed1995

Expression of p53 protein has no independent prognostic value in breast cancer.

A series of 392 female breast carcinomas was analysed immunohistochemically for expression of p53 protein with special emphasis on the role of p53 as an independent prognostic factor. Altogether, 54.8 per cent of the carcinomas expressed p53 protein, with the mean [standard error (SE)] fraction of positive nuclei being 17.1 per cent (1.2 per cent). Expression of p53 protein was independent of tumour metastasis at diagnosis, axillary lymph node status, tumour diameter, histological type, tubule formation, proportion of intraductal growth, margin formation, necrosis, DNA ploidy, and S-phase fraction. A high fraction of p53-positive nuclei was significantly related to patient age under 70 years, high grade, severe nuclear pleomorphism, dense infiltration of tumour by lymphocytes, high mitotic index, and high apoptotic index (for all, P < 0.05). Impaired survival probability in the entire cohort (P = 0.05) and in the axillary lymph node-positive (ANP) tumours (P = 0.015) was associated with a fraction of p53-positive nuclei less than 25 per cent, while in the axillary lymph node-negative (ANN) tumours, expression of p53 had no prognostic value. In multivariate analysis, independent prognostic predictors included axillary lymph node status, tumour diameter, and mitotic index. In the ANN tumours, tumour diameter, fraction of p53-positive nuclei, and tumour grade were independent prognostic factors, whereas in the ANP tumours, diameter and mitotic index were the two independent prognostic factors. The results suggest that abnormal expression of p53 protein is only a weak independent prognostic factor in female breast cancer.

Adult↗

PubMed1995

Expression of retinoblastoma gene protein (Rb) in breast cancer as related to established prognostic factors and survival.

The expression of retinoblastoma gene product (Rb protein) was studied by immunohistochemical analysis of 205 cases of breast cancer. Rb protein was invariably expressed in non-neoblastic breast epithelium, in dysplastic and hyperblastic lesions adjacent to tumours, and none of the breast tumours was totally negative for Rb protein. According to the scoring system used, the expression of Rb protein was abnormal in 36.6% of cases. Abnormal expression of Rb protein was significantly related to grade (P < 0.00004), type (P = 0.0183), margin formation (P = 0.0116), DNA ploidy (P < 0.0002) and nuclear pleomorphism (P < 0.0001). Abnormal expression of Rb protein was related to high S phase fraction (P = 0.004), high mitotic index (P < 0.001) and high morphometric nuclear factor values (P < 0.01). The expression of Rb protein had no prognostic value in univariate or multivariate analysis. The results show that the tumour suppressor gene Rb participates in the growth regulation of breast cancer cells in vivo, but immunohistochemical assessment of the expression of Rb protein has no prognostic significance in clinical breast cancer over already established prognostic factors.

Adult↗

PubMed1995

Expression of tumour-suppressor gene Rb, apoptosis-suppressing protein Bcl-2 and c-Myc have no independent prognostic value in renal adenocarcinoma.

The expression of retinoblastoma (Rb), c-Myc and Bcl-2 proteins was studied by immunohistochemical methods in 104 cases of renal adenocarcinoma. One tumour was completely negative for Rb protein and altered expression pattern was detected in 36% of cases. A low fraction of Rb-positive nuclei was related to high grade (P = 0.016) and high mitotic index (P = 0.012). Twenty-eight per cent of the tumours expressed c-Myc in cancer cell nuclei and 87% showed cytoplasmic positivity. Cytoplasmic expression of c-Myc was related to high grade (P = 0.002), while nuclear expression of c-Myc was related to small tumour diameter (P = 0.034), low T category (P = 0.04), low mitotic index (P = 0.019) and expression of c-ErbB-2 (P = 0.0007). Overexpression of c-myc predicted favourable outcome in M0 tumours (P = 0.0157). Bcl-2 was expressed in 20% of tumours and it was related to small tumour size (P < 0.0001), low T category (P < 0.0001), lack of venous invasion (P = 0.008), node negativity (P = 0.015) and absence of metastasis (P = 0.017). In multivariate analysis the expression of Rb, Bcl-2 and c-Myc had no independent prognostic value over T category (P < 0.001), mitotic index (P = 0.008) and combined nuclear grade (P = 0.056).

Adenocarcinoma↗

PubMed1995

Fatty acid composition of breast adipose tissue in breast cancer patients and in patients with benign breast disease.

Fatty acid composition of triglycerides (TGs) and phospholipids (PLs) in breast adipose tissue was analyzed in 73 female breast cancer patients and 55 patients with benign breast disease. No differences were observed in the dietary intake of the major fatty acids (i.e., palmitic, stearic, oleic, and linoleic acids) or in the proportion of TGs and PLs in breast adipose tissue between the two groups. In postmenopausal women, however, the dietary intake of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) was significantly lower in the breast cancer patients than in patients with benign breast disease. Accordingly, the percentage of docosahexaenoic acid of PLs in breast adipose tissue was significantly lower in breast cancer patients than in patients with benign breast disease among postmenopausal women. The stage of the breast cancer did not contribute to the observed alterations of fatty acid composition of PLs. Consonant with the previous epidemiologic data, the present results suggest that intake of the long-chain n-3 fatty acids (mainly derived from fish) may have a protective effect against breast cancer, particularly in postmenopausal women.

Adipose Tissue↗

PubMed1995

Tumour-associated trypsin inhibitor (TATI) in patients with colorectal cancer: a comparison with CEA, CA 50 and CA 242.

A prospective study of 62 patients with colorectal cancer was carried out to evaluate the value of tumour-associated trypsin inhibitor (TATI) in the diagnosis and staging of this disease. The reference group consisted of 97 patients with benign gastrointestinal disease. Increased serum TATI levels were detected in 46 patients with colorectal cancer (sensitivity 74%), and the highest mean values were measured in the patients with stage II cancer. The frequency of elevated values was not affected by the stage of the disease, however. There were altogether 64 false positives (specificity 34%). In comparison to CEA and CA 242, TATI showed higher sensitivity at low (< 40%) specificity levels, but it was less sensitive at high (70-95%) specificity levels. The performance of the CA 50 test was poorest both at high and low specificity levels. The various combinations of TATI and other markers (two tests positive) did not offer any further advantage as compared to CEA alone. A marginally significant positive correlation (p = 0.07) was found between serum TATI and CEA values in colorectal cancer patients. The results suggest that TATI is a very sensitive marker in colorectal cancer, but its utility is limited because of its low specificity in symptomatic patients. Concomitant measurement of TATI and other markers does not seem to give any further benefit, and nor does TATI seem to have any significant value in staging of the disease. Our results also indicate that CEA is probably the best current test in colorectal cancer.

Adult↗

PubMed1995

The value of history-taking, physical examination, and computer assistance in the diagnosis of acute appendicitis in patients more than 50 years old.

BACKGROUND: The accuracy of the clinical diagnosis of acute appendicitis in patients more than 50 years old was studied in connection with the Research Committee of the World Organization of Gastroenterology (OMGE) survey of acute abdominal pain. Criteria for inclusion and the diagnostic criteria in this prospective study were those set out by the OMGE Research Committee. METHODS: 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 diagnosis of the patients. Twenty-three preoperative 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 appendicitis in patients more than 50 years old were tenderness (relative risk (RR) = 39.4), rigidity (RR = 18.8), and pain at diagnosis (RR = 11.0). The sensitivity of the preoperative clinical decision is detecting acute appendicitis in the aged was 0.87, with a specificity of 0.92, an efficiency of 0.91 and a usefulness index (UI) of 0.69. The computer-aided diagnostic score (DS) reached a sensitivity of 0.92 in detecting acute appendicitis, with a specificity of 0.90 and an efficiency of 0.90. When the patients with a DS value between -0.47 and 0.07 were considered nondefined (n = 43, follow-up required before the decision to operate), the efficiency of the computer-aided diagnosis in detecting acute appendicitis in the aged improved to 0.97. In patients more than 50 years old whose body temperature was available (n = 374), tenderness, rigidity, location of pain at diagnosis, and body temperature predicted significantly acute appendicitis. At a cut-off level of -1.49 the diagnostic score reached a sensitivity of 0.94 in detecting acute appendicitis, with a specificity of 0.91, an efficiency of 0.92 and a UI of 0.80. When the patients with a DS value between -1.49 and 0.46 were considered nondefined (n = 43, follow-up required before the decision to operate), the sensitivity of the computer-aided diagnosis in detecting acute appendicitis in the aged was 0.92, with a specificity of 0.99 and an efficiency of 0.98, and the UI improved to 0.84. CONCLUSION: Acute abdominal pain at the right lower quadrant, with tenderness, rigidity, and increased body temperature (> or = 37.1 degrees C), is indicative of acute appendicitis in patients more than 50 years old. The diagnostic scoring system did perform well, increasing the sensitivity, specificity, efficiency, and usefulness index of the diagnosis of acute appendicitis in the aged.

Acute Disease↗

PubMed1994

Expression of proliferating cell nuclear antigen (PC10), p53 protein and c-erbB-2 in renal adenocarcinoma.

Expressions of proliferating cell nuclear antigen (PC10), p53 protein (CMI) and c-erbB-2 (NCL-1) were immunohistochemically analysed in 123 renal adenocarcinomas with known follow-up data. c-erbB-2 protein was weakly and focally expressed in 10% of the tumours, and the expression was not related to clinical or histological variables or survival. p53 protein was expressed in 33% of the tumours. Expression of p53 protein was independent of stage, grade and prognosis, while expressions of c-erbB-2 and p53 were weakly interrelated. Proliferating cell nuclear antigen was expressed in all tumours, and the fraction of PC10-positive nuclei was significantly related to grade, stage and prognosis. Multivariate analysis of clinical, histological and immunohistochemical prognostic factors indicated that the extent of the tumour, its histological differentiation and proliferation rate of the cancer cells are the most important prognostic factors. Recurrence-free survival was related to the fraction of PC10-positive nuclei, histological differentiation, sex and expression of p53 protein. Over-expression of p53 protein was related to a long recurrence-free survival. Our results show that PC10 immunolabelling can be used to determine the prognostic category in renal adenocarcinoma, whereas the expressions of p53 protein or c-erbB-2 are only weak prognostic indicators.

Adenocarcinoma↗

PubMed1994

Tumour-associated trypsin inhibitor in the diagnosis of pancreatic carcinoma.

The serum values of tumour-associated trypsin inhibitor (TATI) were measured in a prospective series of 97 patients with jaundice, 36 patients with unjaundiced cholestasis and 21 patients with suspicion of chronic pancreatitis or a pancreatic tumour, to assess its value in diagnosing pancreatic cancer. There were altogether 15 patients with cancer of the pancreas and 2 patients with cancer of the papilla of Vater. The highest serum TATI values were noticed in patients with choledocholithiasis, and raised values were also seen in patients with malignant disease of the liver or bile ducts. In the patients with pancreatic cancer, chronic pancreatitis or benign liver disease, the serum TATI values showed lower levels. The sensitivity of TATI in diagnosing pancreatic cancer was 41.1% with a specificity of 63.5% and an efficiency of 61.0%. In comparison to carcinoembryonic antigen (CEA), carbohydrate antigens CA 50, CA 242, tissue polypeptide antigen and tissue polypeptide-specific antigen, TATI showed a lower diagnostic value. When TATI was analysed in combination with the other markers (two tests positive), the combination of CEA with TATI reached the highest specificity (95.6%), efficiency (89.6%) and positive likelihood ratio (9.3). The results suggest that the diagnostic value of TATI is inferior to that of the established markers, but because of its different nature, it may be of help when used in combination as a complementary serum tumour marker in the diagnosis of pancreatic cancer.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1994

Acute appendicitis in patients over the age of 65 years; comparison of clinical and computer based decision making.

The role of clinical and computer based decision in the diagnosis of acute appendicitis in the elderly was studied in connection with the Research Committee of the World Organization of Gastroenterology (OMGE) survey of acute abdominal pain. A total of 220 patients over the age of 65 years presenting with acute abdominal pain were included in the study at the Central Hospital of Savonlinna and at the University Hospital of Tampere. Twenty-two preoperative clinical history variables, 14 clinical signs and three tests were evaluated in a single variable and multivariate analysis to find the best combination of predictors of acute appendicitis in the aged. In order to sum up the contributions of independent diagnostic factors, a diagnostic score (DS) was built: DS = 2.81 x (rectal digital tenderness; 1 = yes, 0 = no) + 2.54 x (rigidity; 1 = yes, 0 = no) + 2.06 x (renal tenderness; 1 = no, 0 = yes) + 2.33 x (bowel sounds; 1 = normal, 2 = absent/abnormal) - 8.13. The sensitivity of preoperative clinical decision in detecting acute appendicitis in the aged was 0.79 with a specificity of 0.92, an efficiency of 0.90 and usefulness index (UI) of 0.56. At a cut-off level of -2.78 the DS reached a sensitivity of 0.84 in detecting acute appendicitis with a specificity of 0.87, an efficiency of 0.87 and UI of 0.68. When the patients with a DS value between -2.78 and -0.45 were considered as non-defined (n = 28, follow-up required before the decision to operate), the sensitivity of the computer-aided diagnosis in detecting acute appendicitis in the elderly was 0.77 with a specificity of 0.97, an efficiency of 0.96 and UI of 0.57. In the elderly patients where a leucocyte count was available (n = 157), location of pain, rectal digital tenderness and leucocyte count predicted significantly acute appendicitis. At a cut-off level of -2.62 the DS reached a sensitivity of 0.81 in detecting acute appendicitis with a specificity of 0.92, an efficiency of 0.91 and UI of 0.59. When the patients with a DS value between -2.62 and 0.06 were considered as nondefined (n = 12, follow-up required before the decision to operate), the sensitivity of the computer-aided diagnosis (leucocyte count available) in detecting acute appendicitis in the elderly improved to 0.86 with a specificity of 0.94, an efficiency of 0.93 and UI of 0.69. In our study the diagnostic scoring system for the elderly performed well considering the simple nature of its structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Pain↗

PubMed1994

A prospective study of serum tumour markers carcinoembryonic antigen, carbohydrate antigens 50 and 242, tissue polypeptide antigen and tissue polypeptide specific antigen in the diagnosis of pancreatic cancer with special reference to multivariate diagnostic score.

The aim of this study was to assess by a stepwise multivariate discriminant analysis the value of four current serum tumour markers - carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 and tissue polypeptide antigen (TPA) - and a new serum tumour marker, tissue polypeptide specific antigen (TPS), in the diagnosis of pancreatic cancer. The serum values were measured in a prospective series of patients with jaundice, with unjaundiced cholestasis and with a suspicion of chronic pancreatitis or a pancreatic tumour (n = 193). There were 24 patients with a cancer of the pancreas and two patients with a cancer of the papilla of Vater in this series. Our results showed that CA 50 (P < 0.001) and TPA (P < 0.01) were the best marker tests in predicting pancreatic malignancy. Also, the TPS (P = 0.07) and CA 242 (P = 0.08) tests showed marginally significant independent discriminating power, while the CEA test did not (P = 0.12). In order to sum up the contributions of different markers, a diagnostic score (DSI) was developed. The discrimination function was: DS1 = CA 50 x 1.75 + TPA x 0.62 + TPS x (-0.37) + CA 242 x (-1.21). The sensitivity of DS1 in detecting pancreatic cancer was 36% with a specificity of 90% and an efficiency of 82%. When the combination of CA 50 and TPA was used as a test, the discrimination function (DS2) was: DS2 = CA 50 x 0.69 + TPA x 0.67. The sensitivity of DS2 was 44% with a 88% specificity and an efficiency of 82%. According to this analysis, the further advantage gained by a computer-aided scoring system seems to be limited, since despite the considerably high specificity and efficiency its sensitivity remained low. In the present analysis the best combination in diagnosing pancreatic cancer was the combination of CA 50 and TPA.

Adult↗

PubMed1994

Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis.

The expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in 234 cases of transitional cell bladder cancer. EGFR was overexpressed in 35% of cases and distinct nuclear localisation of EGFR positivity was found in 31% of the tumours. Overexpression was related to invasive growth, grade 2-3 histology, non-papillary type, DNA aneuploidy and high proliferation rate of cancer cells. The expressions of p53 and EGFR were interrelated, while expression of c-erbB-2 was independent of EGFR expression. Progression of superficial tumours, recurrence-free survival and survival were independently related to overexpression of EGFR in multivariate analysis. T category, S-phase fraction and non-papillary type included all the available prognostic information when the entire cohort was analysed by multivariate methods. The results show that overexpression of EGFR is related to several malignant features and prognosis in superficial bladder cancer. Moreover, the results suggest that overexpression of EGFR is usually a late event in bladder cancer development related to genetic instability rather than an early event in malignant transformation. Further studies are still needed to establish whether the direct measurement of cell proliferation or analysis of growth factor receptors and other oncoproteins gives more accurate prognostic information in bladder cancer.

Adolescent↗