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G van Leenders

Publications and source records attributed to G van Leenders.

2 recordsLinked to original sources

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↗

Demonstration of intermediate cells during human prostate epithelial differentiation in situ and in vitro using triple-staining confocal scanning microscopy.

In human prostate epithelium, morphologically basal and luminal cells can be discriminated. The basal cell layer that putatively contains progenitor cells of the secretory epithelium is characterized by the expression of keratins (K) 5 and 14. Luminal cells represent the secretory compartment of the epithelium and express K8 and 18. We developed a technique for the simultaneous analysis of K5, 14, and 18 to identify intermediate cell stages in the prostate epithelium and to study the dynamic aspects of its differentiation in vitro. Nonmalignant prostate tissue and primary epithelial cultures were immunohistochemically characterized using triple staining with antibodies for K5, K14, and K18. Antibodies for K18 and K5 were conjugated directly with fluorochromes Alexa 488 and 546. K14 was visualized indirectly with streptavidin-Cy5. Keratin expression was analyzed by confocal scanning microscopy. The occurrence of exocrine and neuroendocrine differentiation in culture was determined via antibodies to prostate-specific antigen (PSA), chromogranin A, and serotonin. We found that basal cells expressed either K5(++)/14(++)/18+ or K5(++)/18+. The majority of luminal cells expressed K18(++), but colocalization of K5+/18(++) were recognized. Epithelial monolayer cultures predominantly revealed the basal cell phenotype K5(++)/14(++)/18+, whereas intermediate subpopulations expressing K5+/14+/18(++) and K5+/18(++) were also identified. On confluence, differentiation was induced as multicellular gland-like buds, and extensions became evident on top of the monolayer. These structures were composed of K18(++)- and K5+/18(+)-positive cell clusters surrounded by phenotypically basal cells. Few multicellular structures and cells in the monolayer showed exocrine differentiation (PSA+), but expression of chromogranin A and serotonin was absent. We conclude that simultaneous evaluation of keratin expression is useful for analyzing epithelial differentiation in the prostate. During this process, putative stem cells phenotypically resembling K5(++)/14(++)/18+ differentiate toward luminal cells (K18(++)) via intermediate cell stages, as identified by up-regulation of K18 and down-regulation of K5 and 14.

Cell Differentiation↗