PubMed Health⌕ Search

Biomedical subjects

J A van der Laak

Publications and source records attributed to J A van der Laak.

18 recordsLinked to original sources
PubMed2001

Improved prediction of metastasis in tongue carcinomas, combining vascular and nuclear tumor parameters.

BACKGROUND: Predicting the presence of metastasis, based on tumor or tumor-related characteristics is of utmost importance. The authors studied the significance of tumor DNA features and tumor-related angiogenesis to predict the occurrence of metastasis in squamous cell carcinomas (SCCs) of the tongue. METHODS: Paraplast blocks from resection specimens of 20 metastasized and 20 nonmetastasized SCCs of the tongue with a minimum follow-up of 24 months were used. Tissue sections were stained with anti-CD34 monoclonal antibodies for vessel visualization, and according to Feulgen to stain DNA. Using image analysis, data from both stainings were computed for each of the 40 carcinomas. A logistic regression model to predict the presence of metastasis, based on vascular and nuclear morphology features, was developed. RESULTS: The intratumor variation of chromatin condensation and the percentage vessels smaller than 5 microm in diameter were selected for the model. The model correctly predicted metastasis in 90% of patients and excluded metastasis correctly in 75% of nonmetastasized tumors. Taking into account the prevalence of metastasis in SCC of the tongue of between 30% and 60%, this means a predictive value for a negative outcome of between 95% and 83%. CONCLUSIONS: The proposed model shows an improvement of predictive values compared with previous models with single parameters. Therefore, a multiparameter model appears to predict the multiparameter process of metastasis better.

Carcinoma, Squamous Cell↗
PubMed2001

Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats.

PURPOSE: The mechanisms that cause diabetes to impair the development of anastomotic strength in the intestine are poorly understood. We investigated whether short-term uncontrolled diabetes causes alterations in microscopic aspects of anastomoses from the ileum and colon. METHODS: Eighteen Wistar rats were rendered diabetic one week before operation by intravenous streptozotocin injection (50 mg/kg), resulting in nonfasting blood glucose levels of approximately 20 mmol/l. Another 18 age-matched rats were used as controls with a normal blood glucose range of 5 to 7 mmol/l. All rats underwent resection and anastomosis of both the ileum and colon. Animals were killed at one, three, or seven days after operation. Cellular and architectural parameters of anastomotic healing were scored in hematoxylin and eosin-stained sections. Anastomotic collagen content was analyzed by image analysis in picrosirius red-stained sections. RESULTS: Anastomotic necrosis, edema, and epithelial recovery were not affected by diabetes. In diabetic rats, the number of polymorphonuclear cells and macrophages was significantly (P = 0.025 and 0.0002, respectively) increased in ileal anastomoses one and three days after operation. In colonic anastomoses, the number of polymorphonuclear cells was increased at one (P = 0.001) and seven (P = 0.014) days after operation. Repair of the submucosal-muscular layer in colonic anastomoses from diabetic rats was impaired seven days after surgery (P = 0.0071), but in ileal anastomoses no difference was found. In the anastomotic area, collagen deposition at postoperative Days 1, 3, and 7 remained unaffected by diabetes. CONCLUSION: Experimental diabetes leads to alterations in cellular components involved in the early phase of repair of intestinal anastomoses but not to a reduced accumulation of wound collagen.

Anastomosis, Surgical↗
PubMed2001

Progressive histopathological changes in pancreatic islets of Zucker Diabetic Fatty rats.

Thus far, histopathological changes in the pancreatic islets of Zucker Diabetic Fatty (ZDF) rats, an animal model of type 2 diabetes mellitus (or non-insulin-dependent diabetes mellitus), have only been studied in male rats and in 18-weeks old rats or younger. In this study, we have examined in both male and female ZDF rats the histopathological changes longitudinally, from 6 to 32 weeks of age. We studied islet architecture and cellular distribution of the various islet hormones both in ZDF and control rats. In the ZDF rats, aging was initially associated with an enlargement of the islets. From 18 weeks onwards, no further enlargement was noted but islet boundaries became increasingly irregular, leading to the appearance of projections of endocrine cells into the surrounding exocrine tissue. At the islet boundaries as well as within the islets progressive fibrosis was observed with increasing amounts of collagen and reticular fibers. In the islets, staining intensity of both insulin and islet amyloid polypeptide (IAPP) increased slightly till 10 weeks of age and thereafter decreased rapidly. In contrast, the staining intensities of glucagon, somatostatin, and pancreatic polypeptide (PP) did not change. Even at the age of 32 weeks, just the beta-cells and not the other endocrine islet cells appear to be affected. In control rats, aging evoked only minor changes. Thus, we observed that during prolonged development of diabetes mellitus in both male and female ZDF rats histopathological changes in the pancreatic islets became progressively more severe, eventually leading to disintegration of the islets.

Aging↗
PubMed2001

Quantification of tumour vascularity in squamous cell carcinoma of the tongue using CARD amplification, a systematic sampling technique, and true colour image analysis.

The aims of this study of head and neck tissue samples were to develop an immunohistochemical protocol based on the catalysed reporter deposition (CARD) technique to enhance staining results for use in automated true colour image analysis, to assess the reproducibility of systematic tissue sampling in the angiogenic hot spot selection, and quantification of microvessel density (MVD) and other vessel characteristics. The latter data were compared between six metastasised tongue squamous cell carcinomas, vs. four non-metastasised. In comparison to the standard immunohistochemical protocol with anti-CD34 antibodies, CARD amplification resulted in both more intensely stained and larger numbers of vessels. Averaging the 10 most vascularised fields of the 40 to 60 systematically sampled fields in a tissue section resulted in an overall acceptable interobserver reproducibility for most assessed vessel parameters (r> or =0.76 and p< or =0.01). The percentage vessels with diameter <5 microm was significantly higher in the non-metastasised tongue carcinomas (p=0.02). However, for a number of tumours the effect of tissue sampling was significant. We conclude that CARD amplification is needed for reliable segmentation of vessels by image analysis systems, and that tumour heterogeneity is a limiting factor for all procedures in which tumour vascularity is assessed in a single tissue section. Figures on http://www.esacp.org/acp/2001/22-4/hannen.htm.

Antigens, CD34↗
PubMed2001

Microvessel density: correlation between contrast ultrasonography and histology of prostate cancer.

OBJECTIVE: Increased microvessel density (MVD) of prostate cancer seems to be associated with poor prognosis and higher stage. Assessment of MVD using noninvasive methods could be of use in the work-up of patients with prostate cancer. The aim of the present study was to correlate three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) findings with MVD characteristics of radical prostatectomy specimens. METHODS: Seven patients with biopsy-proven prostate cancer had 3D-CE-PDU investigations 2-3 weeks after prostate biopsies were taken and prior to radical prostatectomy. The investigations were performed using Levovist contrast agent (Schering AG, Berlin, Germany) in combination with a Voluson 530D ultrasound scanner (Kretz AG, Zipf, Austria). The 7 patients were selected because of lateralization of the contrast enhancement. Histology slides were made of the side with 'contrast enhancement' and of the contralateral 'unenhanced' side and stained according to the catalyzed reporter deposition (CARD) amplification procedure, and MVD parameters were obtained. RESULTS: In all patients the MVD count of the 'enhanced' side was higher than the MVD count of the 'unenhanced' side, averaging 1.93 times higher. On histology all enhanced lesions proved to contain prostate cancer tissue (average maximum diameter 25 mm (range 17-31)). Two patients had a small bilateral tumor lesion (4 and 5 mm respectively) and in total 5 patients had even smaller satellite lesions (1-2 mm). The smaller lesions were not identified using 3D-CE-PDU. CONCLUSIONS: The present study shows that 3D power Doppler contrast ultrasonography is a minimally invasive imaging modality, which has the potential to visualize lesions with increased MVD. This property of 3D-CE-PDU could be used in the detection of prostate cancer.

Aged↗
PubMed2000

Decreased expression of Ki-67 in atrophic cervical epithelium of post-menopausal women.

Papanicolaou-stained cervical smears (Pap smears) of post-menopausal women often present difficulties in distinguishing atrophic cervical epithelium from high-grade cervical intraepithelial neoplasia (CIN2-3). The aim of this study was to disclose differences in proliferative activity in normal cervical epithelium, cervical atrophy, and high-grade CIN lesions, in order to develop specific and sensitive classifiers to discriminate between cervical atrophy and high-grade CIN, both in cervical smears and in tissue sections. A case-control study was done on 83 patients. Proliferative activity was assessed in histological sections using the monoclonal antibody MIB1. An image analysis system was used to characterize different proliferation-associated features. Preceding Pap smears were restained with MIB1 and proliferative activity was measured by a point-counting procedure, carried out on a training set of 32 cases and a test set of 51 cases. In cervical atrophy, proliferative activity was significantly lower than in normal epithelium (p<0.001). Proliferative activity measured in both biopsies and cervical smears was considerably higher in high-grade CIN than in normal epithelium (p<0.001). Discriminant analyses resulted in four classifiers, based on proliferation parameters, to discriminate between cervical atrophy and high-grade CIN, and between CIN2 and CIN3, in biopsy specimens and cervical smears, respectively. The two classifiers for biopsy specimens resulted in 100% correct classification. Application of the classifier obtained from the training set of Pap smears resulted in 100% correct classification of the Pap smears in the test set. The classifier to discriminate between CIN2 and CIN3 in Pap smears, obtained from 36 patients, resulted in 87% and 90% correct classification, respectively.

Aged↗
PubMed1999

Development and validation of a computerized cytomorphometric method to assess the maturation of vaginal epithelial cells.

BACKGROUND: After menopause, declining levels of estrogens may cause vaginal discomfort, or so-called "vaginal atrophy." Evaluation of therapies for vaginal atrophy may be performed using the so-called "maturation index." The maturation index is expressed as the percentage of (para)-basal, intermediate, and superficial epithelial cells in a vaginal smear. Manual assessment of the maturation index is subject to inter- and intraobserver variations. In this study, assessment of the maturation of cells in vaginal smears using automated image analysis was investigated. MATERIALS AND METHODS: Automated assessment, using a commercially available image analysis system, was performed on hematoxylin-eosin-stained cytospin specimens. A training set was constructed by an experienced cytotechnologist, based upon visual classification of stored grey value images. From this, two discriminant functions (DFs) were calculated capable of classifying cells in one of the three types. These cell classifiers were capable of classifying 97% of the cells correctly. Data from automated assessment were compared with those of classical manual counting. Specimens of 13 mature and 6 atrophic vaginal specimens were assessed in duplicate, both manually and by image analysis, using the DFs. RESULTS: No significant interobserver effect was found for image analysis, whereas a significant effect was found for manual counting. Both methods were able to distinguish between matured and atrophic specimens. CONCLUSIONS: It was concluded that for assessment of vaginal maturation, the use of automated image analysis systems is recommended. Besides increased reproducibility, image analysis systems yield additional data describing the size and shape of the cytoplasm and nucleus of cells, which might increase discriminating power.

Adult↗
PubMed1999

Transient tenascin enhancement is an early event after androgen ablation in rat prostate.

Tenascin (tenascin-C), a mesenchymal glycoprotein, is expressed in many tissue remodeling processes. We evaluated tenascin expression during androgen-deprivation-related involution of the rat prostate. At set intervals following castration and subsequent testosterone repletion, prostates were removed in 30 adult rats. Each prostate was immunostained with a polyclonal antiserum against rat tenascin and keratin antibodies specifically directed against exocrine basal cells and luminal cells in the prostate glandular structure. Morphologic impressions were semiquantatively evaluated using a computer-assisted image analysis system. Rat prostates showed a transient increase in the periglandular tenascin expression directly following castration that reached a maximum at day 3. At day 6, tenascin expression was similar to control prostates. This was accompanied by a decrease of cells in the luminal cell layer. The weakest tenascin immunoreactivity was noted on day 14 after androgen withdrawal. This process was reversed by androgen repletion. This study shows that in the rat prostate tenascin expression may be androgen dependent and that during androgen deprivation-related involution tenascin expression is probably associated with tissue remodeling by stromal-epithelial interactions.

Androgens↗
PubMed1998

An improved procedure to quantify tumour vascularity using true colour image analysis. Comparison with the manual hot-spot procedure in a human melanoma xenograft model.

In a number of recent papers, the degree of tumour vascularization has been described as a promising new prognostic factor. Methods for the assessment of vascular density involve immunohistochemical staining of the vasculature, followed by counting the number of vessel profiles in the angiogenic hot spot. One of the problems of this procedure is the selection of the angiogenic hot spot, which has been described as being subject to inter-observer variation. In this study, the value of true colour image analysis in reducing inter-observer variation has been assessed. Highly (MV3) and poorly (M14) vascularized human melanoma xenografts were used to evaluate the image analysis procedure, and the image analysis results were compared with results from the conventional manual hot-spot procedure. Assessment by image analysis was performed on measurement fields covering the entire tumour tissue specimens rather than on a single hot-spot field. Also, by selecting the most densely vascularized area from all fields assessed by the semi-automatic procedure, it was possible to objectify the hot spot selection (automated hot-spot procedure). Manual assessment showed a good correlation between two independent observers for MV3 xenografts (r = 0.74, P = 0.014), but a poor correlation for M14 xenographs (r = 0.4, P > 0.05). Automated assessment by different operators showed good correlations for both MV3 xenografts (r = 0.99, P < 0.001) and M14 xenografts (r = 0.80, P = 0.006). It is concluded that although both manual vessel counting and semi-automated image analysis can differentiate between the level of vascularization in the two types of xenograft (P < 0.001 for both methods), the automated method is favourable in that it showed no significant inter-observer effects. In M14 xenografts, the manual hot-spot vessel densities did not correlate well with the automated hot-spot densities (r = 0.27, P > 0.05), indicating that selection of angiogenic hot spots in this tumour type is indeed subject to observer bias. The automated hot-spot vessel densities were a reliable indicator of overall tumour vessel density in both tumour types. Image analysis allows analysis of vessel subclasses based on morphological criteria such as vessel profile area or diameter. In the model system used, the discrimination between MV3 and M14 xenografts was further enhanced by selectively examining vessels with diameters between 6 and 9 microns (P < 0.0005). In conclusion, image analysis appears to offer an objective and more reproducible method to quantify tumour vascularity than manual counting of vessel profiles in the hot spot. Analysis of subclasses of vessels may further enhance the value of vessel density measurements in discriminating between tumour types differing in biological behaviour.

Animals↗
PubMed1998

An image analysis study on nuclear morphology in metastasized and non-metastasized squamous cell carcinomas of the tongue.

In a retrospective case-control study on 46 metastasized and 34 non-metastasized primary tongue carcinomas, the nuclear morphology and chromatin pattern were assessed in 3 microns thick, formalin-fixed, paraffin-embedded, and Feulgen-stained tissue sections of surgical resection specimens, by means of high-resolution computer-assisted image analysis. The aim of this study was to disclose differences in karyometric features, such as nuclear size-, shape-, and chromatin-pattern features, between these groups, with a view to developing a discriminant function that can predict the occurrence of metastasis for the individual patient. In addition, the lymph node metastases of 31 patients and the normal tongue epithelium of 21 patients were also assessed, to study the possible differences between these two groups and primary tumours. In the metastasized tumours, the chromatin was significantly more condensed (P = 0.01) and exhibited significantly less variation in chromatin condensation (P < 0.001) than in the group of non-metastasized carcinomas. Comparison of lymph node metastases with their primary tumours disclosed only minor differences in chromatin pattern. These findings suggest that only minor genetic differences exist between primary tongue carcinomas and their metastases. Tumour cells of tongue carcinomas showed highly significant differences from cells of normal tongue mucosa for most karyometric features. Logistic regression analysis resulted in a classifier, based on the circularity of the nucleus (CIRC) and the standard deviation of the chromatin condensation (SD COND), to predict the occurrence of lymph node metastases. After cross-validation, the percentages of correct classifications in the group of metastasized and non-metastasized tumours were 72 and 62 per cent, respectively. These results are comparable to the classification results obtained from a classifier based on the clinical T-stage, but our karyometric classification results show a much more equal distribution between the sensitivity and specificity. Karyometric features appeared to be more appropriate to predict metastases than biomarkers such as p53, bcl-2, and Ki-67.

Carcinoma, Squamous Cell↗
PubMed1998

Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy.

Because glioblastoma multiforme (GBM) frequently shows striking, glomeruloid microvascular proliferation (MVP), this tumor has become a strong candidate for anti-angiogenic therapy. However, the efficacy of anti-angiogenic treatment may rather be determined by the extent of classic angiogenesis with the formation of delicate microvascular sprouts. Therefore, this study differentially quantifies the microvascular changes in supratentorial diffuse astrocytic neoplasms by computerized image analysis of histological sections in which the microvessels were highlighted by a combined anti-collagen IV/MIB-1 staining. Four microvascular parameters (number, area, perimeter, diameter), the cellularity of the glial tissue, and the MIB-1 labeling index were assessed in biopsies of astrocytoma (A, n = 13), anaplastic astrocytoma (AA, n = 14), and GBM (n = 20), and in normal cerebral cortex (n = 7) and white matter (n = 7). In As and AAs, the microvascular parameters were not significantly different from each other, and the microvascular changes were generally limited compared with WM and CX. In contrast, in GBMs the microvascular parameters were highly variable, and their overall mean value was significantly increased compared with As and AAs (ranging from 1.3x for vessel diameter to 3.3x for vessel area). Our study indicates that not only glomeruloid MVP, but also classic angiogenesis, occurs mainly and only locally in GBMs. Thus, this study provides evidence that As and AAs are not good candidates for anti-angiogenic therapy. The efficacy of such therapy for GBMs awaits further evaluation.

Antigens, Nuclear↗
PubMed1997

Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential.

We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.

Animals↗
PubMed1996

MIB1, a promising marker for the classification of cervical intraepithelial neoplasia.

Formalin-fixed and paraffin-embedded tissue specimens of normal and dysplastic cervical epithelia (five CIN1, seven CIN2, five CIN3, and five normal) were assessed by an immunoperoxidase technique, using the monoclonal antibody MIB1, regonizing a formalin-fixation-resistant epitope on the cell proliferation-associated Ki-67 antigen. An image analysis system was used to measure four parameters associated with proliferative activity: the Ki-67 labelling index (LI), the number of Ki-67-positive nuclei per unit length of basement membrane, and the maximum value and 90th percentile of the relative distances of Ki-67-positive nuclei from the basement membrane. All these four proliferation-related parameters were highly correlated with the grade of dysplastic change in the epithelium (0.90 < r < 0.97, p < 0.0001). The best correlation was found for the 90th percentile of the relative distance and with this parameter all CIN lesions could be correctly classified. The means and standard deviations of the Ki-67 LIs in normal epithelium, CIN1, CIN2, and CIN3 lesions were 0.07 +/- 0.03, 0.16 +/- 0.03, 0.25 +/- 0.06, and 0.39 +/- 0.06, respectively. These findings support the theory that CIN involves a progressive dysfunction of the proliferative activity of cervical epithelial cells. Image analysis of MIB1 is a promising alternative method for the objective, reproducible, and reliable classification of dysplastic changes in cervical epithelium.

Antibodies, Monoclonal↗
PubMed1995

Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy.

Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.

Albuminuria↗
PubMed1994

Correlation of histology and acoustic parameters of liver tissue on a microscopic scale.

The correlation of several acoustic parameters with histological features was investigated in healthy White New Zealander rabbit liver (n = 10). Thin sections (10 microns) were studied by means of a light microscope in combination with a digital image processing system. Adjacent thick sections (250 microns) were studied by means of a custom-designed acoustic microscope. Markers of black silk suture material, that could be identified both optically and acoustically, enabled the spatial correlation of both imaging modalities. Acoustic images were reconstructed from the velocity of ultrasound, the attenuation at the central frequency (30 MHz), the attenuation spectral slope, the backscatter spectral slope and the backscatter at the central frequency. The measurements comprised the frequency range from 10 to 50 MHz, yielding a resolution of approximately 50 microns. From the thin sections (10 microns) the local histological composition was obtained by digital segmentation techniques. The features that were segmented are: the collagen rich fibrous tissue content, the area lumina, the area interstitial spaces, the number density of nuclei and the area parenchymal tissue. Correlation techniques revealed that the main feature responsible for attenuation is collagen. There was a fair correlation between area lumina and attenuation, but this was caused by a high correlation between the collagen that surrounds the lumina, and attenuation. No correlation was found between any histological feature and backscatter parameters or velocity.

Animals↗
PubMed1994

A new method to correlate acoustic spectroscopic microscopy (30 MHz) and light microscopy.

A powerful new method is used to investigate the correlation between light microscopic and acoustic properties of biological tissues. Specimens of liver were sectioned into successive slices, 250 micrometers and 10 micrometers thick. The thick sections were investigated acoustically, the thin sections by means of light microscopy. Markers that could be detected and located, both optically and acoustically, were used to find and reconstruct corresponding regions in the acoustic and optical sections (2.5 x 2.5 mm). Parameter images were reconstructed from the sections investigated acoustically. The acoustic parameters were attenuation at 30 MHz, the slope of the attenuation spectrum (between 10 and 50 MHz), backscattering at 30 MHz, the slope of the backscattering spectrum (between 10 and 50 MHz) and the local ultrasound velocity. Acoustic images were obtained in the frequency range from 10 to 50 MHz, yielding a lateral resolution of about 50 micrometers. The sections for light microscopy were stained according to the Goldner trichrome staining technique. The histological composition was determined quantitatively, using digital image segmentation techniques. The percentage of collagen-rich fibrous tissue, luminal structure and interstitial spaces, and the number of nuclei were calculated for regions of 250 x 250 micrometers. These histological features were correlated with the acoustic parameters obtained from the corresponding regions in adjacent sections. It was thus possible to find the histological components responsible for acoustic parameters.

Animals↗
PubMed1994

Quantitative immunohistological analysis of the microvasculature in untreated human glioblastoma multiforme. Computer-assisted image analysis of whole-tumor sections.

Because histologically prominent microvascular proliferation is frequently present in glioblastoma multiforme, it has been hypothesized that this neoplasm is particularly dependent on neovascularization for its continued growth and that antiangiogenic therapy might be especially useful. To quantify the histological aspects of microvascular proliferation in glioma, a feasible and reproducible method was developed for computer-assisted image analysis of the visualized microvasculature in glial tissue. This method was used to compare several vascular parameters in histological whole-tumor sections of untreated human glioblastoma multiforme with those in histologically normal cerebral cortex and white matter. There was a significant increase in mean number, area, and perimeter of blood vessels per microscopic field in glioblastoma multiforme compared to normal cerebral white matter. In a substantial number of tumor fields, however, the vascular density was in the same range as that of normal cerebral white matter. The striking heterogeneity of the microvasculature within glioblastoma multiforme was illustrated by the significantly higher standard deviation for the vascular parameters in tumor tissue. The results of this study suggest that many regions of glioblastomas multiforme are not overtly angiogenesis dependent and may be difficult to treat by antiangiogenic therapy alone.

Adult↗