Geir Egil Eide

Expression of Enhancer of Zeste Homologue 2 Is Significantly Associated with Increased Tumor Cell Proliferation and Is a Marker of Aggressive Breast Cancer

The polycomb group protein enhancer of zeste homologue 2 (EZH2) has been linked to invasive properties of aggressive breast cancer. In this report, tissue microarray analysis of 190 breast carcinomas from a nested case-control study shows that EZH2 is significantly associated with interval breast cancers. Further, a strong relationship was found with tumor cell proliferation (by Ki-67 expression), locally advanced disease, metastasis at presentation, markers of the basal epithelial phenotype (positivity for cytokeratin 5/6 or P-cadherin), and p53 status. EZH2 expression was also significantly associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype. For prediction of aggressive disease (any event of locally advanced disease, lymph node spread, or distant spread), EZH2 was the only variable of significance in multivariate analysis, whereas no additional information was given by Ki-67. Although EZH2 expression was significant in univariate survival analysis, only tumor cell proliferation and lymph node status were significant in the final multivariate model. In conclusion, our findings indicate an important relationship not only between EZH2 and markers of tumor cell proliferation but also with aggressive disease. These findings might be practically important and relevant because the polycomb group proteins have recently been suggested as candidates for targeted therapy.

A Basal Epithelial Phenotype Is More Frequent in Interval Breast Cancers Compared with Screen Detected Tumors

Interval breast cancer reduce the effectiveness of mammography screening programs. We studied 95 interval cancers, diagnosed during 1996 to 2001 as part of the population-based Norwegian Breast Cancer Screening Program. These cases were matched on size (±2.0 mm) to 95 screen-detected breast cancers, and the tumors were compared by immunohistochemical methods using tissue microarrays. Patients with interval cancers were more likely to be younger [odds ratio (OR), 4.7; P = 0.0001], to have dense breasts (OR, 3.4; P = 0.004), and to have estrogen receptor–negative tumors (OR, 2.6, P = 0.01), and p53 expression was more frequent (OR, 4.0; P = 0.001). Notably, interval cancers were more likely to have a basal epithelial phenotype, in that expression of cytokeratin 5/6 (OR, 2.3; P = 0.04) and P-cadherin (OR, 2.5; P = 0.04) was more frequent in interval cases than in size-matched, screen-detected tumors. In a logistic regression model, p53 expression, age, and breast density were independent predictors of interval cancers. Our data suggest that breast cancers with a basal epithelial phenotype are more likely than nonbasal breast cancers to present between regular mammograms.

Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study

Aims: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population‐based, complete cohort of young preterms approaching adulthood. Methods. Forty‐six preterms with gestational age ±28 wk or birthweight ±1000g, born between 1982 and 1985, were compared to the temporally nearest term‐born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. Results: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctors diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty‐six percent of preterms had a positive methacholine provocation test compared to 26% of controls.

Postoperative complications and mortality after surgery for gastric cancer.

Complication rates and postoperative mortality were studied in 1010 consecutive patients entered into the Norwegian Stomach Cancer Trial. Twenty-eight per cent of the patients had one or more complications (31% of the men and 21% of the women). General complications (pneumonia, thromboembolic, and cardiac) were most frequent. The postoperative mortality rate for resected patients was 8.3% (63 of 763). Complication and mortality rates were highest for proximal resections (52% and 16%) followed by total gastrectomy (38% and 8%), subtotal resection (28% and 10%), and distal resection (19% and 7%). By logistic regression analysis it was found that age, sex, operative procedure, prophylactic antibiotics, and splenectomy were significantly related to postoperative complications. The odds ratio for complication for men versus women was 1.75: for no antibiotics versus antibiotic prophylaxis it was 2.5. Relative to distal resection the odds ratio for complications after subtotal resection was 2.2, for total gastrectomy was 3.9, and for proximal resection was 7.6. Age and sex were the only factors that affected operative mortality. The odds ratio for mortality for men versus women was 2.3. The odds ratio for operative mortality was 2.2 when the age of the patient increased with 10 years.

Sequential and average attributable fractions as aids in the selection of preventive strategies

Methods for estimating the attributable fraction based on a multivariate model for a dichotomous response have been extensively developed in the last decade. These methods provide the means for calculating the total attributable fraction for a set of exposure variables possibly adjusted for a set of confounding variables. In this paper, a procedure for stepwise calculation of attributable fractions is outlined. The purpose is to study the effect on risk of disease of preventing several exposures, one at a time, in different orderings. This procedure introduces the concepts of sequential and average attributable fractions as aids for attributing the risk of disease to different exposures. The procedure and concepts are illustrated by analyzing data from a cross-sectional study on the prevalence of some frequent symptoms of lung disease.

Oligodendroglioma. Histologic Evaluation and Prognosis

Abstract All oligodendrogliomas registered in Norway during a 25-year period (1953–1977) were studied to establish the frequency of different histologic features and to compare them with survival data of the patients. The minimum observation time was five years. The original tumor specimens from 208 patients were independently reexamined by two pathologists. The characteristic Oligodendroglioma of this series was of medium cell density (53% of lesions), with moderate nuclear atypia, with vascular endothelial proliferation (53%), calcification (56%), with from one to five mitotic figures per ten high power fields, and without microcystic degenerative changes (58%). Subpial tumor cell infiltration, perivascular lymphocytic infiltration and local leptomeningeal invasion were present in a minority of cases. In 11 cases autopsy material was the only source of diagnosis. Microcysts, necrosis, and cell density were the only histologic features of prognostic significance. Subpial infiltrative growth was of suggestive prognostic value. There was no significant association between the number of mitotic figures and survival. Vascular endothelial proliferation, calcification, pronounced nuclear atypia, perivascular lymphocytic infiltration and local leptomeningeal invasion were of no significant prognostic value. Age at operation did not alter these conclusions, neither did sex nor duration of preoperative symptoms.

Quantitative Computed Tomography Measures of Emphysema and Airway Wall Thickness Are Related to Respiratory Symptoms

RATIONALE There is limited knowledge about the relationship between respiratory symptoms and quantitative high-resolution computed tomography measures of emphysema and airway wall thickness. OBJECTIVES To describe the ability of these measures of emphysema and airway wall thickness to predict respiratory symptoms in subjects with and without chronic obstructive pulmonary disease (COPD). METHODS We included 463 subjects with chronic obstructive pulmonary disease (COPD) (65% men) and 488 subjects without COPD (53% men). All subjects were current or ex-smokers older than 40 years. They underwent spirometry and high-resolution computed tomography examination, and completed an American Thoracic Society questionnaire on respiratory symptoms. MEASUREMENTS AND MAIN RESULTS Median (25th percentile, 75th percentile) percent low-attenuation areas less than -950 Hounsfield units (%LAA) was 7.0 (2.2, 17.8) in subjects with COPD and 0.5 (0.2, 1.3) in subjects without COPD. Mean (SD) standardized airway wall thickness (AWT) at an internal perimeter of 10 mm (AWT-Pi10) was 4.94 (0.33) mm in subjects with COPD and 4.77 (0.29) in subjects without COPD. Both %LAA and AWT-Pi10 were independently and significantly related to the level of dyspnea among subjects with COPD, even after adjustments for percent predicted FEV(1). AWT-Pi10 was significantly related to cough and wheezing in subjects with COPD, and to wheezing in subjects without COPD. Odds ratios (95% confidence intervals) for increased dyspnea in subjects with COPD and in subjects without COPD were 1.9 (1.5-2.3) and 1.9 (0.6-6.6) per 10% increase in %LAA, and 1.07 (1.01-1.14) and 1.11 (0.99-1.24) per 0.1-mm increase in AWT-Pi10, respectively. CONCLUSIONS Quantitative computed tomography assessment of the lung parenchyma and airways may be used to explain the presence of respiratory symptoms beyond the information offered by spirometry.

Nonresponse in a community cohort study: predictors and consequences for exposure-disease associations.

We have assessed predictors for response in a Norwegian community cohort study, with an 11-year follow-up. We also examined to what extent the association of gender, age, and smoking to the incidence of respiratory symptoms and asthma differed if the analyses were based on the 65% (n = 2,079) initial responders, or were based on the 89% (n = 2,819) who responded after three reminders. The associations between the six symptoms/asthma and the gender, age, and smoking groups amounted to 42 odds ratios. The adjusted odds ratio for responding at follow-up was 1.39 (95% CI: 1.01, 1.90) for those being middle aged at baseline compared to younger subjects. The adjusted odds ratios for responding at follow-up for those being students, unemployed, or retired at baseline were 0.50 (95% CI: 0.35, 0.73), 0.29 (95% CI: 0.16, 0.55), 0.21 (95% CI: 0.13, 0.36), respectively, compared to being employed. Of the 42 odds ratios mentioned above, 25 differed less than 10% when comparing the initial and all respondents. Twelve differed 10-20% and five differed 20-45%. The study indicates that to ensure a high participation rate in a follow-up study one should pay special attention to those being late responders, unemployed, retired, or students at baseline. No overt differences were observed in the gender, age, and, smoking associations to the respiratory disorders when the analyses were based on the initial compared to all respondents.

Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking.

We investigated how quantitative high-resolution computed tomography (HRCT) measures of emphysema and airway wall thickness (AWT) vary with sex, age and smoking history. We included 463 chronic obstructive pulmonary disease (COPD) cases and 431 controls. All included subjects were current or ex-smokers aged ≥40 yrs, and all underwent spirometry and HRCT examination. The HRCT images were quantitatively assessed, providing indices on lung density and airway dimensions. The median (25–75th percentile) %LAA950 (% low-attenuation area < -950 HU) was 8.9 (3–19) and 4.7 (1–16) in male and female COPD cases, respectively, and 0.71 (0.3–1.6) and 0.32 (0.1–0.8) in male and female controls, respectively. %LAA950 was higher in ex-smokers and increased with increasing age and with increasing number of pack-years. The mean±sd standardised AWT was 0.504±0.030 and 0.474±0.031 in male and female COPD cases, respectively, and 0.488±0.028 and 0.463±0.025 in male and female controls, respectively. AWT decreased with increasing age in cases, and increased with the degree of current smoking in all subjects. We found significant differences in quantitative HRCT measures of emphysema and AWT between varying sex, age and smoking groups of both control and COPD subjects.

Overweight and obesity in Norwegian children: prevalence and socio-demographic risk factors

Aim:  The aim of this study was to estimate the prevalence of childhood overweight and obesity and to identify socio‐demographic risk factors in Norwegian children.