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L J Van den Broek

Publications and source records attributed to L J Van den Broek.

5 recordsLinked to original sources
PubMed1999

Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis.

The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established. However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have investigated the role of several (onco)genes in cervical carcinoma. In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor (EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases, tumor diameter, vessel invasion, and disease-free and overall survival. Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this expression was correlated to p53 expression (P<0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free (P = 0.002) and overall survival (P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph node status. Gene amplification was found for EGFR (four cases), c-erbB-2/ neu (two cases), and c-myc (six cases). In two tumors, rearrangement of c-myc was found, probably due to the integration of HPV. In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.

Adult↗
PubMed1997

Distribution of extracellular matrix components in adamantinoma of long bones suggests fibrous-to-epithelial transformation.

Adamantinoma of long bones is a rare skeletal tumor of unknown origin with epithelial and fibrous elements. The ill-defined distinction between the two components in some cases earlier led to the assumption that these might be derived from the same (mesenchymal) stem cell. In this study, we investigated the distribution of extracellular matrix components in 21 adamantinomas by immunohistochemistry, to gain information on the interaction between the epithelial and fibrous parts of the tumor. Collagens I and III, and fibronectin were generally present in the (osteo-)fibrous tissue of adamantinoma but lacked in the epithelial aggregates. There was a clear relation between the identification of the epithelial and fibrous components at the histological level, and the staining for basement membrane proteins collagen IV and laminin. Prominent areas with cohesive epithelial growth were surrounded by continuous basement membranes, whereas less distinct epithelial islands contained membrane interruptions or had no surrounding basement membrane at all. Tenascin stained intensely surrounding demarcated epithelial aggregates, but weakly or absent more distantly. Osteofibrous dysplasia (OFD)-like tumors displayed local spicular density or pericellular staining of basement membrane factors in fields of isolated keratin-positive cells. These findings suggest that in adamantinoma individual epithelial cells transform from the osteofibrous tissue and thereafter form clusters of epithelium, as can be recognized in classic adamantinoma. This is in analogy to the development of the glandular component of biphasic synovial sarcoma. The fibrous part of adamantinoma is, however, believed to be of benign nature. These results further substantiate the hypothesis of osteofibrous dysplasia being a potential precursor lesion of adamantinoma.

Ameloblastoma↗
PubMed1990

Development of progressive glomerulosclerosis in experimental chronic serum sickness.

A rat model of chronic serum sickness was used to study the pathogenesis of progressive glomerulosclerosis complicating experimental immune-complex glomerulonephritis. Chronic serum sickness was induced by immunising rats with bovine serum albumin followed by intraperitoneal administration of the antigen. Early lesions consisted of mesangial deposits of rat immunoglobulins, followed later by transient subendothelial and persistent subepithelial immune aggregates. On the basis of the peak level of proteinuria around day 80, three groups of rats were distinguished: I physiological proteinuria; II 50-500 mg/24 h; and III greater than 500 mg/24 h. The animals were killed at day 220 and the presence of mesangial proliferation, epithelial proliferation, and synechiae, as well as focal glomerulosclerosis was scored. It appeared that all and only proteinuric animals developed progressive glomerulosclerosis, although all three groups of animals passed through a phase with mesangial and subendothelial immune deposits. A strong correlation was found between the degree of proteinuria and the proportion of glomeruli affected. We conclude that the combination of mesangial and subendothelial deposits on the one hand and subepithelial deposits associated with increased protein loss on the other constitute a conditio sine qua non for the development of progressive glomerulosclerosis in this model. The use of specific antibodies to investigate the composition of the sclerotic lesions showed the presence of laminin and type IV collagen, but not of types I and III collagen in sclerotic areas of glomeruli. This indicates that the development of progressive glomerulosclerosis in this model is due to an increased production of glomerular basement membrane components by presumably solely glomerular cells after the occurrence of immunological glomerular injury.

Animals↗
PubMed1986

Neuroendocrine cells in colorectal adenomas.

A consecutive series of 218 endoscopically resected colorectal adenomas was investigated for the occurrence of neuroendocrine cells. In 59 per cent of these adenomas argyrophil cells were detected. In 8 per cent of the adenomas these cells were numerous and so intricately blended in with the other cell types that they were regarded as an intrinsic part of the tumour. In these adenomas subsequently immunocytochemistry revealed the presence of the neuro-hormonal peptides glucagon, pancreatic polypeptide and somatostatin as well as serotonin, in a pattern similar to that seen in normal colorectal mucosa. The presence of neuroendocrine cells did not correlate with any clinical or pathological parameter. The occurrence of neuroendocrine cells in colorectal adenomas is in agreement with the unitarian theory of the development of the various epithelial cell types in large bowel mucosa.

Adenoma↗