Abstract
Pathological diagnosis of prostate adenocarcinoma often requires complementary methods. On prostate biopsy tissue from 39 patients including benign nodular hyperplasia (BNH), atypical adenomatous hyperplasia (AAH), and adenocarcinomas, we have performed combined histochemical-immunohistochemical stainings for argyrophilic nucleolar organizer regions (AgNORs) and glandular basal cells. After ascertaining the pathology, we have analyzed the number, roundness, area, and fractal dimension of individual AgNORs or of their skeleton-filtered maps. We have optimized here for the first time a combination of AgNOR morphological denominators that would reflect best the differences between these pathologies. The analysis of AgNORs' roundness, averaged from large composite images, revealed clear-cut lower values in adenocarcinomas compared to benign and atypical lesions but with no differences between different Gleason scores. Fractal dimension (FD) of AgNOR silhouettes not only revealed significant lower values for global cancer images compared to AAH and BNH images, but was also able to differentiate between Gleason pattern 2 and Gleason patterns 3–5 adenocarcinomas. Plotting the frequency distribution of the FDs for different pathologies showed clear differences between all Gleason patterns and BNH. Together with existing morphological classifiers, AgNOR analysis might contribute to a faster and more reliable machine-assisted screening of prostatic adenocarcinoma, as an essential aid for pathologists.
Highlights
Prostate cancer is considered the second cause of death by malignant neoplasia in the male population around the world, over 95% of all diagnosed cases being represented by acinar adenocarcinoma [1,2,3]
Techniques such as immunohistochemistry for acinar basal cells [6, 7], the histochemical silver staining for the nucleolar organiser regions (AgNORs) [8], and genetic testings have brought an invaluable support in establishing the correct diagnosis
Besides algorithms that attempted to recognize glandular morphology in order to identify malignant prostate tissue areas, argyrophilic nucleolar organizer regions (AgNORs) silver impregnation has been utilized in various studies based on manual, semiautomatic, or fully automatic scoring methods, taking into account the number, aggregation, and size of argyrophilic dots in relation to clinicopathological prognostic parameters for prostatic carcinoma [13,14,15,16]
Summary
Prostate cancer is considered the second cause of death by malignant neoplasia in the male population around the world, over 95% of all diagnosed cases being represented by acinar adenocarcinoma [1,2,3]. Pathological diagnosis of prostate neoplasia is sometimes cumbersome and the differential diagnosis needs to be made with atypical benign lesions. In these cases, techniques such as immunohistochemistry for acinar basal cells [6, 7], the histochemical silver staining for the nucleolar organiser regions (AgNORs) [8], and genetic testings have brought an invaluable support in establishing the correct diagnosis [9, 10]. Nucleolar organizing regions (NORs) represent fragments of ribosomal DNA involved in transcription of ribosomal RNA, which due to their association with nonhistonic argyrophilic proteins may be observed and quantified after precipitation of silver nitrate [8, 22]
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