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A Van Daele

Publications and source records attributed to A Van Daele.

14 recordsLinked to original sources

Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions.

BACKGROUND: To identify nuclei and lesions with great specificity, a large set of karyometric features is arranged in the form of a linear profile, called a nuclear signature. The karyometric feature values are normalized as z-values. Their ordering along the profile axis is arbitrary but consistent. The profile of the nuclear signature is distinctive; it can be characterized by a new set of variables called contour features. A number of data reduction methods are introduced and their performance is compared with that of the karyometric features in the classification of prostatic, colonic, and esophageal lesions. METHODS: Contour characteristics were reduced to descriptive statistics of the set of z-values in the nuclear signature and to sequence information. The contour features derived were (1) relative frequencies of occurrence of z-values and of their differences and (2) co-occurrence statistics, run lengths of z-values, and statistics of higher-order dependencies. Performance was evaluated by comparing classification scores of diagnostic groups. RESULTS: Rates for correct classification by karyometric features alone and contour features alone indicate equivalent performance. Classification by a combined set of features led to an increase in correct classification. CONCLUSIONS: Image analysis and subsequent data reduction of nuclear signatures of contour features is a novel method, providing quantitative information that may lead to an effective identification of nuclei and lesions.

Cell Nucleus↗

Fibrous intimal thickening at implantation as a risk factor for the outcome of cadaveric renal allografts.

BACKGROUND: During the past decade, the donor age of cadaveric renal allografts steadily increased. Because cerebrovascular injury is the main cause of death in this donor population, an increased prevalence of atherosclerotic lesions in the retrieved grafts could be anticipated. In a prospective study, we investigated the predictive value of morphologic lesions at implantation for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years. METHODS: In 50 consecutive adult recipients of a cadaveric renal allograft, under cyclosporine-based regimen, implantation biopsies and subsequent protocol biopsies at 18 months were performed, and morphometrically analyzed for the extent of glomerulosclerosis, interstitial fibrosis, and atherosclerosis. Risk factors were assessed at implantation and during the subsequent observation period of 18 months. Endpoints for this study were: the 24-hr creatinine clearance (normalized for body surface area) and the fractional interstitial volume at 1 1/2 years. RESULTS: In multivariate analysis, fibrous intimal thickening at implantation (FIT) was the main determinant of the functional and morphologic outcome at 1 1/2 years. FIT represented a relative risk of 4.55 for interstitial fibrosis (95% CI=1.855-11.138), and 1.89 for impaired renal function (95% CI=1.185-3.007) at 1 1/2 years. FIT adversely affected fractional interstitial volume at 1 1/2 years (34.3 vs. 27.7%, P=0.004), as well as renal function (54 vs. 68 ml/min/1.73 m2, P=0.028). CONCLUSIONS: Fibrous intimal thickening at implantation is a determinant risk factor for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years.

Adult↗

The association between vascular endothelial growth factor, microvessel density and clinicopathological features in invasive cervical cancer.

OBJECTIVE: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features. STUDY DESIGN: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD. RESULTS: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression. CONCLUSION: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.

Adenocarcinoma↗

Proliferation, DNA ploidy, p53 overexpression and nuclear DNA fragmentation in six equine melanocytic tumours.

Melanocytic tumours are a well-known clinical and pathological entity in horses, but further phenotypic characterization of these tumours is lacking. Six melanocytic tumours from five horses (two metastatic and four benign) were examined by Ki67, PCNA and p53 immunostaining, DNA nick end labelling (Tunel) and Feulgen staining. The stainings were evaluated using quantitative image analysis. The resulting parameters of growth fraction (Ki67), S-phase index (PCNA), p53 index, apoptotic index, DNA index, nuclear diameter, ploidy balance, proliferation index (Feulgen) and hyperploidy were analysed. The metastatic melanomas showed overexpression of p53 in a large portion of the cells. Apoptosis was also found in the metastatic melanomas. No differences were found in growth fraction, S-phase index (PCNA) nor in DNA configuration between the metastatic and the benign tumours. No immunohistochemical evidence of mutant p53 could be found in the tumours. In conclusion, melanocytic tumours in horses seem to have different phenotypic characteristics in comparison with melanocytic tumours in dogs, cats and humans, especially with respect to proliferative activity of the benign tumours. Therefore, markers put forward in these other species for predicting the clinical behaviour of the melanomas seem to be of no value in the horse. Moreover, quantitative DNA changes or p53 mutations do not seem to be involved in tumourogenesis in these cases.

Animals↗

Validation of nuclear texture, density, morphometry and tissue syntactic structure analysis as prognosticators of cervical carcinoma.

OBJECTIVE: To evaluate the performance of karyometry and histometry in the prediction of survival, recurrence and response of early-stage invasive cervical carcinoma. STUDY DESIGN: Nuclear morphometry, chromatin texture and tissue architecture (characterized by syntactic structure analysis) were measured using a semiautomated image analysis system on 46 cases of Feulgen-stained tissue sections. The performance of the features was compared to that of clinical features, reported to be the best prognosticators until now, such as age, lympho-vascular permeation, histologic type, stage and grade. A K nearest neighbor classifier was used for classification. RESULTS: In the prediction of three-year survival, recurrence and response, syntactic structure analysis proved to be the best performer. Classification rates were, respectively, 100%, 94.4% and 94.5%. In all classifications, karyometric and histometric features outperformed clinical features. In general, the best performing features described differences in second-order population statistics (standard deviations). CONCLUSION: The results show that a quantitative analysis based on nuclear morphology, chromatin texture and histology can be considered an excellent aid in the prognosis of invasive cervical carcinoma. The measurements are not hampered by the need to undertake complete resections and are suited to daily practice when implemented in a semiautomated image analysis system.

Adult↗

Value of morphometry, texture analysis, densitometry, and histometry in the differential diagnosis and prognosis of malignant mesothelioma.

Malignant mesothelioma is a tumour with increasing incidence due to widespread use of its causative agent, asbestos, in the past decades. The poor survival necessitates a correct differentiation from other lesions at the same site, such as hyperplastic mesothelium and carcinomas metastatic to pleura or peritoneum. Since genetic and immunohistochemical markers are not absolutely differentiating, the diagnosis is based on the histology complemented with (immuno)histochemistry. However, as the tumour presents itself in numerous heterogeneous histological forms, visual evaluation is extremely difficult. In order to evaluate the prognostic and diagnostic performance of syntactic structure analysis (SSA), chromatin texture analysis, densitometry, and morphometry, an automated KNN-classification system has been used to compare Feulgen-stained tissue sections of hyperplastic mesothelium, malignant mesothelioma, and pulmonary adenocarcinoma. In addition, we also studied most discriminative aspects in the differentiation, typing, and prediction of survival. The results indicate that for the diagnosis of malignant mesothelioma, chromatin texture parameters outperform SSA, densitometry, and morphometry (recognition score=96.8 per cent). Most discriminative parameters highlight spatial patterns of the chromatin distribution that are hard to appraise visually and directly show the benefits of a quantitative approach. Typing of the tumour is best described by SSA parameters, relating to the spatial arrangement of the cells in the tissue (recognition score=94.9 per cent). In survival time classifications, chromatin texture yields the highest recognition score (82.9 per cent), although accurate estimations are unreliable due to a large degree of misclassification.

Adenocarcinoma↗

Angiogenesis in cervical intraepithelial neoplasia and the risk of recurrence.

OBJECTIVE: We sought to investigate whether angiogenesis can predict the risk of recurrence of cervical intraepithelial neoplasia after treatment. STUDY DESIGN: Microvessel density was studied in 75 patients with grade 3 cervical intraepithelial neoplasia and in 20 patients with microinvasive squamous carcinoma (International Federation of Gynecology and Obstetrics stage IA1) of the uterine cervix by staining representative tissue sections with the specific endothelial marker anti-CD31. The microvessel density was determined with a digital image analyzer. The results were correlated with clinical and histopathologic data. RESULTS: The mean vessel density was 264 per field (range, 86-674 per field) in grade 3 cervical intraepithelial neoplasia and 378 per field (range, 161-848 per field; P = .001) in microinvasive squamous carcinoma. Thirteen patients with grade 3 cervical intraepithelial neoplasia had recurrent cervical intraepithelial neoplasia (microvessel density, recurrent vs nonrecurrent; not significant). Multiple regression analysis in the noninvasive group confirmed that the mean vessel density (P = .121) had no prognostic value. Furthermore, it showed that the age at diagnosis (P = .011), menopausal status (P = .052), and treatment modality (P = .022) proved to be independent prognostic factors for recurrence. CONCLUSIONS: During the progression from noninvasive to microinvasive cervical carcinoma, the microvessel density increases significantly. However, the vessel density does not predict recurrence of noninvasive lesions.

Adult↗

Biochemical and histopathological changes in nephrectomized mice.

Renal failure is characterized by the retention of nitrogenous metabolites such as urea, creatinine (CTN) and other guanidino compounds (GCs), uric acid, and hippuric acid, which could be related to the clinical syndrome associated with renal insufficiency. A model of renal failure has been developed in male C57BL x Swiss-Webster mice using nephrectomy (NX) and/or arterial ligation. A sham group (group A) and two nephrectomized groups, group B (one kidney removed) and group C (one kidney removed and ligation of the contralateral anterior artery branch), were studied. Ten days postsurgery, morphological and functional indices of renal failure were investigated. Nephrectomized mice manifested features of renal failure like polyuria and wasting. CTN clearance (CTN[Cl]) decreased by +/-26% in group B and +/-33% in group C as compared with the control values. Marked increases in the plasma concentration of guanidinosuccinic acid ([GSA] fourfold) and guanidine ([G] twofold) were observed in the experimental animals. CTN and alpha-keto-delta-guanidinovaleric acid (alpha-keto-delta-GVA) reached levels of, respectively, 1.5-fold and twofold those of controls. Urinary GSA excretion increased and guanidinoacetic acid (GAA) excretion decreased about twofold in group C. GSA increases (2.6-fold) were also observed in the brain in group C, in addition to a significant increase of G (2.5-fold) and gamma-guanidinobutyric acid ([GBA] 1.5-fold). Finally, the extent of NX was found to be 45.2% in group B and 71.4% in group C. Light microscopy revealed an expansion and increase in cellularity of the mesangium of the glomeruli, particularly in group C. A significant correlation (r = .574, P < .0001) was found between CTN(Cl) and the degree of NX as calculated from the remaining functional area. These data suggest that the model can be used as a tool for further pathophysiological and/or behavioral investigations of renal failure.

Animals↗

Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer.

Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy.

Adult↗

Evaluation of tumour angiogenesis as a prognostic marker in malignant mesothelioma.

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumours. Malignant mesothelioma (MM) of the pleura is a highly invasive tumour with a poor prognosis. In the present study, microvascular quantification was undertaken on 25 specimens of mesothelioma and 15 specimens of non-neoplastic mesothelium (NNM), by staining for the antigens CD34 and CD31. Areas of highest intratumoural microvascular density (IMD) were identified and counted either manually (mIMD) or on a computerized image analysis system (CIAS; iIMD). The two IMDs were significantly correlated with each other (r = 0.736; P < 0.001). The average IMD for MM was significantly (P < 0.001) higher than in NNM. Moreover, each unit increment in iIMD for MM, when regarded as a continuous variable, was significantly (P = 0.001) associated with an increased hazard of about 4 per cent. When regarded as a categorical variable, the patients in the highest tertile (> 58 vessels/field) had a significantly (P < 0.01; log-rank test) shorter survival than patients in the lowest tertile (< 45 vessels/field). This association was independent of the age of the patient and of the histological type or grade of the MM. No association was noted with p53 immunoexpression. Although the mean vascular area of blood vessels measured on the CIAS did not correlate with survival, assessment of IMDs can be an important independent prognostic indicator in malignant mesothelioma.

Antigens, CD34↗

Evaluation and prognostic value of DNA content and of morphometric parameters in malignant mesothelioma using digital image analysis.

Fifty-seven cases of malignant mesothelioma were analyzed for nuclear diameter, DNA content and ploidy-related parameters, using Feulgen stained paraffin sections with a digital imaging analysis system. Thirty cases had a mean nuclear diameter > 7 microns and 31 cases were classified as near-diploid. A statistically significant correlation between survival and the mean nuclear diameter (P = 0.0006) and between survival and DNA index (P = 0.007) was obtained. For other DNA content parameters (proliferation index, 5c exceeding rate), only one of the two statistical tests showed a significant correlation with survival while the other test was of borderline significance. In this malignant mesothelioma population, the prognosis for patients with the epithelial type was better than for those with sarcomatous tumours (P = 0.01). In this population of patients, about half of the malignant mesotheliomas were aneuploid. The mean nuclear diameter, DNA index analysis and proliferation index analysis of the tumour cells on Feulgen stained paraffin sections can be used as independent prognostic parameters.

Cell Nucleus↗

Stereological evaluation of malignant mesothelioma versus benign pleural hyperplasia.

The differential diagnosis between malignant mesothelioma and benign pleural hyperplasia constitutes a well-known problem. In the present study we examined unbiased stereological techniques to assess the mean nuclear volume (MNV) using the point-sampled intercepts (PSI) in 37 cases of malignant mesothelioma and in 28 cases of benign pleural hyperplasia. Neither the use of different fixatives nor the histological type of malignant mesothelioma produced any significant difference on the measured nuclear volume. The differences observed between the MNV data obtained from benign pleural hyperplasia and those from any of the three types of malignant mesothelioma were found to be highly significant. All lesions with an MNV larger than 250 microns3 were found in our study to correspond to the malignant mesothelioma type, while an MNV that was smaller than 200 microns3 could only be detected in benign specimens. These observations lead us to propose the MNV measurement using PSI as an additional tool to enhance the differential diagnosis of malignant mesothelioma versus benign pleural hyperplasia.

Cell Nucleus↗

Detection of numerical chromosomal aberrations in paraffin-embedded malignant pleural mesothelioma by non-isotopic in situ hybridization.

An in situ hybridization (ISH) study on paraffin sections of 13 malignant mesotheliomas was performed to detect numerical chromosomal aberrations with biotin-labelled DNA probes specific for the centromeric regions of chromosomes 1, 3, 6, 7, 11, and 17. All chromosomes contributed to numerical changes, which can be summarized as follows: first, a monosomy for chromosome 6 was found in one case; second, in five cases a trisomy for at least one chromosome was detected; and third, in seven cases a pentasomy or a higher polysomy was found for at least one chromosome. Although these data have to be confirmed on a larger group of patients, survival analysis of this group showed no significant difference between the first and second groups taken together and the third group. In this study no specific numerical chromosomal aberrations were identified. Nevertheless, numerical gains appear to be more frequent than has previously been shown by karyotype analysis.

Chromosome Aberrations↗

Influence of econazole and 5-fluorocytosine on the ultrastructure of Aspergillus fumigatus and the cytochemical localization of calcium ions as measured by laser microprobe mass analysis.

The ultrastructural changes and the localization of Ca++ ions have been investigated in Aspergillus fumigatus after exposure in vitro to econazole (50 micrograms ml-1) and to 5-fluorocytosine (100 micrograms ml-1) for 24 h. The changes obtained with econazole concerned the cell periphery, necrotization of mitochondria and hyperactivity of the central vacuole. After cytochemical Ca++ localization a marked increase in precipitate was observed on mitochondria, vacuoles and collapsed membranes, compared to the control. Laser microprobe mass analysis confirmed that the measured amount of Ca++ ions corresponded to the degree of precipitate formation in the different cellular compartments. After exposure to 5-fluorocytosine, abnormal behaviour of the nuclei and internal lipidification of the mitochondria and of the cytoplasm were seen. No discernible Ca++ activity was present on the cellular structures by cytochemical localization. Assay by laser microprobe mass analysis, however, showed a slight increase in Ca++ which points to a structural bonding of the Ca++.

Aspergillus fumigatus↗