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C van de Kaa

Publications and source records attributed to C van de Kaa.

5 recordsLinked to original sources

Molecular changes associated with prostate cancer development.

The epidemiologic characteristics of prostate cancer (PCa) have been recognized for several decades. It is of great importance to understand the factors responsible for prostate carcinogenesis, why some carcinomas remain "clinically silent" during life, whereas other tumors progress to present clinically and may lead to PCa-related death. A better understanding of these mechanisms in molecular genetic terms should point to more rational approaches to disease prevention, intervention and treatment. The aim of this review is to provide a comprehensive overview of the current state of knowledge regarding the molecular alterations of PCa.

Androgens↗

Errors in histological grading by prostatic needle biopsy specimens: frequency and predisposing factors.

Sampling error is an inherent problem of prostate biopsy. Consequently, there are problems in determining whether a given carcinoma is clinically significant on the basis of biopsy results. This study assesses the factors that predispose to errors in biopsy grading, as well as the dimensions of sampling error due to these factors. Among 187 cases, biopsy grading error was retrospectively related to grade heterogeneity in the prostate and to biopsy-related factors. Clinically relevant biopsy grading errors occurred in a quarter of the cases. Of all grading errors, at least 17% resulted from misinterpretation by the pathologist only. Overall, prostates with grade heterogeneity revealed grading errors twice as frequently as specimens without grade heterogeneity. In most cases, however, grading error resulted from multiple factors, such as the number and length of cores obtained (p<0.05). This was an important finding because the mean core length was only 9.4 mm, whereas the biopsy needle is designed to obtain cores of 15 mm. Moreover, clinically relevant biopsy grading error had occurred in almost half of the cases when the Gleason score was based on a tumour deposit measvring less than 0.5 mm (p<0.05). The clinical consequences of these findings are important. Clinicians should try to obtain at least six biopsies, each 15 mm in length, to minimize grading error. Pathologists should be cautious in reporting Gleason scores based on tumour lesions smaller than 400x total magnification field. Interpretation could be refined, when necessary, by warning the urologist of the Limitations of the biopsy report.

Aged↗

Heterogeneous expression of E-cadherin and p53 in prostate cancer: clinical implications. BIOMED-II Markers for Prostate Cancer Study Group.

Histologic grade and tumor volume are markers of malignant phenotype. More objective markers, however, have been sought for needle biopsy specimens. The aim of this study was to evaluate how immunohistochemical expression of the potential prognostic markers E-cadherin and p53 in biopsy specimens relates to the expression of these markers in prostatectomy specimens. Therefore, we analyzed 47 prostatectomy specimens and their preoperative biopsy specimens. Fixation of surgical specimens and the immunohistochemical assay for both E-cadherin and p53 expression was optimized. All paraffin blocks containing areas of carcinoma were submitted for immunohistochemical analysis. The prevalence of abnormal p53 immunoreactivity was only 11%. In addition, abnormal p53 expression was virtually restricted to cases that were already identified as having a poor prognosis on the basis of the large volume and the high grade of their carcinomas. In 28% of the cases, we found abnormal immunoreactivity for E-cadherin. These cases revealed considerable heterogeneity in topographic distribution of abnormal expression. The level of sensitivity to the detection of abnormal E-cadherin expression or abnormal p53 in the prostatectomy specimen was 15% and 60%, respectively. In view of the inherent heterogeneity of E-cadherin expression and the low prevalence of abnormal p53 expression, we question the use of these markers for prognostic purposes in needle biopsy specimens. Unless representative sampling by needle biopsy can be assured, the use of E-cadherin expression will be of most value in prostatectomy specimens.

Biopsy↗

Amplification of chromosome subregion 12p11.2-p12.1 in a metastasis of an i(12p)-negative seminoma: relationship to tumor progression?

Cytogenetic analysis of a metastasis of a human testicular germ cell tumor (seminoma) revealed multiple numerical and structural anomalies, including an abnormally banding region (ABR) present on the short arm of one of the chromosome 12 homologs. Fluorescence in situ- and comparative genomic hybridization experiments revealed that the ABR results from the amplification of 12p11.2-p12.1 derived sequences. We speculate that this particular region may harbor gene(s) relevant for testicular germ cell tumor progression.

Adult↗