Morphological identification of the patterns of prostatic intraepithelial neoplasia and their importance

Montironi, Rodolfo

doi:10.1136/jcp.53.9.655

Cited by 63 publications

(47 citation statements)

References 80 publications

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“…To the best of our knowledge, this is the first investigation documenting differences in cell composition in PIN lesions showing different architectural patterns. Previous studies 1,23,24 have either tried to identify cell subpopulations or to define subgroups in highgrade PIN, regardless of its architecture.…”

Section: Discussionmentioning

confidence: 99%

“…PIN is characterized by a spectrum of atypical cytological features ranging from minimal changes to those that are indistinguishable from carcinoma cells. 1,2 The classification of PIN into low-grade and highgrade is chiefly based on the cytological characteristics of the cells. The nuclei of cells composing low-grade PIN are enlarged, vary in size, have a normal or slightly increased chromatin content, and possess small or inconspicuous nucleoli.…”

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confidence: 99%

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Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia

et al. 2004

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This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform highgrade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosinstained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to highgrade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the midabnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia

et al. 2004

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“…31,63,64 Increasing rates of aneuploidy and angiogenesis as the grade of PIN progresses are further evidence that high-grade PIN is a precancer. 1,62,[65][66][67][68] Prostate cancer and high-grade PIN also have similar proliferative and apoptotic indices. 1,3,40,[69][70][71][72][73][74] It is often difficult with small foci in needle biopsies to separate cancer from suspicious foci (atypical small acinar proliferation suspicious for but not diagnostic of malignancy) when there is coexistent high-grade PIN; the difficulty is based on the inability to separate tangential cutting of the larger pre-existing acini of PIN (that may appear as small separate adjacent acini) from the smaller discrete acini of cancer.…”

Section: Diagnostic Criteria Of Pinmentioning

confidence: 99%

High-grade prostatic intraepithelial neoplasia

2004

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High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

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“…Baseline and end-of-study biopsy samples were stained with H&E and examined under light microscopy. Six prespecified morphologic features were identified and ranked orderly: normal tissue, inflammation, simple atrophy, PIA, HG-PIN, and adenocarcinoma (18,19), and each specimen was recorded according to type and location (apex, peripheral zone, transitional and central zones of both lobes, seminal vesicles). Specifically, PIA was identified according to the criteria described as postatrophic hyperplasia in a Working Group Classification of Focal Atrophy of the Prostate (19), which also includes detailed description of simple atrophy features.…”

Section: Analytic Methodsmentioning

confidence: 99%

Phase I-II Trial of Weekly Bicalutamide in Men with Elevated Prostate-Specific Antigen and Negative Prostate Biopsies

Zanardi

Puntoni

Maffezzini

et al. 2009

Cancer Prevention Research

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Background: Men with elevated prostate-specific antigen (PSA) and negative prostate biopsies are at risk for prostate cancer. The antiandrogen bicalutamide has a prolonged half-life, thus potentially allowing an intermittent administration to retain activity while reducing toxicity. We conducted a phase I-II trial of weekly bicalutamide in men with PSA >4 ng/mL and negative biopsies.Methods: Eighty subjects were nonrandomly assigned to a three-arm trial to either bicalutamide 50 mg/wk (n = 26) or 100 mg/wk (n = 28) or no treatment (n = 26) for 6 months. Blood samples were obtained at 0, 3, and 6 months, and prostate biopsies were repeated after 6 months. The outcome measures were 6-month changes of tissue Ki-67 (primary end point), high-grade prostatic intraepithelial neoplasia (HG-PIN), proliferative inflammatory atrophy, circulating PSA, and sex hormones.Results: Ki-67 expression was higher in HG-PIN than in normal tissue (10% versus 3%; P < 0.01) but was not modulated by bicalutamide in normal luminal cells. A trend toward an improvement of HG-PIN status was found in treated subjects (26% improved, 60% had no change, 15% worsened) as compared with the no-treatment arm (4% improved, 83% had no change, 13% worsened; P = 0.07). Proliferative inflammatory atrophy prevalence was not reduced by bicalutamide. Bicalutamide reduced PSA by 50% in both arms and raised testosterone and estradiol levels. Asymptomatic breast swelling was noted in 40% of the treated cases.Conclusions: A weekly administration of bicalutamide seems to be reasonably safe and shows an encouraging signal of activity on HG-PIN prevalence, supporting further studies of this schedule in men at high risk despite the negative primary end-point findings on Ki-67.

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Morphological identification of the patterns of prostatic intraepithelial neoplasia and their importance

Cited by 63 publications

References 80 publications

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia

High-grade prostatic intraepithelial neoplasia

Phase I-II Trial of Weekly Bicalutamide in Men with Elevated Prostate-Specific Antigen and Negative Prostate Biopsies

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