Activation of Wnt/β-catenin signaling in a subpopulation of murine prostate luminal epithelial cells induces high grade prostate intraepithelial neoplasia

Abstract Context.—High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression. Objective.—To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection. Design.—Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma. Results.—Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P = .1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P < .05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10. Conclusion.—These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.

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Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer

Central European Journal of Urology ◽

10.5173/ceju.2016.726 ◽

2016 ◽

Vol 69 (1) ◽

Cited By ~ 2

Keyword(s):

Prostate Cancer ◽

Benign Prostatic Hyperplasia ◽

Intraepithelial Neoplasia ◽

Prostatic Hyperplasia ◽

Microvascular Density ◽

High Grade ◽

Immunohistochemical Expression ◽

Prostate Intraepithelial Neoplasia

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High grade prostate intraepithelial neoplasia (PIN) is a PSA-independent risk factor for prostate cancer in African American men: Results from a pilot study

Cancer Letters ◽

10.1016/j.canlet.2012.12.014 ◽

2013 ◽

Vol 331 (2) ◽

pp. 154-157 ◽

Cited By ~ 6

Author(s):

Ganna Chornokur ◽

Gang Han ◽

Richard Tanner ◽

Hui-Yi Lin ◽

B. Lee Green ◽

...

Keyword(s):

Prostate Cancer ◽

African American ◽

Risk Factor ◽

Pilot Study ◽

Independent Risk Factor ◽

African American Men ◽

Intraepithelial Neoplasia ◽

High Grade ◽

Prostate Intraepithelial Neoplasia

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CELL PROLIFERATION AND VOLUME-WEIGHTED MEAN NUCLEAR VOLUME IN HIGH-GRADE PIN AND ADENOCARCINOMA, COMPARED WITH NORMAL PROSTATE

Image Analysis & Stereology ◽

10.5566/ias.v26.p93-99 ◽

2011 ◽

Vol 26 (2) ◽

pp. 93 ◽

Cited By ~ 3

Author(s):

Fernando Teba ◽

Rocío Martín ◽

Vicente Gómez ◽

Luis M Herranz ◽

Luis Santamaría

Keyword(s):

Basal Layer ◽

Intraepithelial Neoplasia ◽

Nuclear Volume ◽

Nuclear Antigen ◽

High Grade ◽

Basal Cells ◽

Normal Epithelium ◽

Normal Prostate ◽

Prostate Intraepithelial Neoplasia ◽

Malignant Changes

High-grade prostate intraepithelial neoplasia (PIN) is considered a precursor of prostate adenocarcinoma. The aim of this study was to quantitate the differences between basal and luminal cells of PIN in relation to mean nuclear volume (νVnuc), and proliferating cell nuclear antigen labeling index (LIPCNA), and to compare these estimates with those obtained in normal prostate and carcinoma. The epithelium of both normal and PIN specimens was segmented in basal and luminal compartments, and the νVnuc and LIPCNA measured in both strata. νVnuc was significantly lower in normal epithelium than in both PIN and carcinoma. The νVnuc of basal layer of PIN was significantly higher than in luminal stratum. The luminal νVnuc was similar in both PIN and adenocarcinoma. The LIPCNA was greater in PIN and adenocarcinoma than in normal glands. The LIPCNA of basal cells from PIN was similar to that observed in the basal stratum from normal prostate, whereas the luminal proliferation from PIN was similar to that observed in adenocarcinoma. The similarities in nuclear size between PIN and carcinoma are according to the premalignant haracter of PIN. The increase of basal νVnuc in PIN indicates that the changes heralding the progression from PIN to carcinoma are produced in this layer, whereas the nuclear features of the luminal layer are the same to those of the carcinoma. These remarks make sense in reference to the progression of malignant changes from PIN basal layer to PIN luminal layer and from this to carcinoma.

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Ο ρόλος της ολικής και της ελεύθερης τεστοστερόνης ως προγνωστικός δείκτης θετικοποίησης της επαναληπτικής βιοψίας σε ασθενείς με PSA>4ng/ml και προηγούμενη αρνητική βιοψία για καρκίνο προστάτου ή με διάγνωση PIN

10.12681/eadd/47032 ◽

2020 ◽

Author(s):

Αλέξανδρος Φιαμέγκος

Keyword(s):

Prostate Specific Antigen ◽

Specific Antigen ◽

Intraepithelial Neoplasia ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

High Grade ◽

Hormone Binding ◽

Prostate Intraepithelial Neoplasia

ΕΙΣΑΓΩΓΗ: Τα δεδομένα από μελέτες σε πειραματόζωα, κλινικές μελέτες και μελέτες πρόληψης αναδεικνύουν το ρόλο των ανδρογόνων στην ανάπτυξη και την πρόοδο του καρκίνου του προστάτη. Παρόλα αυτά οι επιδημιολογικές μελέτες σε ανθρώπους για την τεστοστερόνη του ορού δεν έχουν αναδείξει ξεκάθαρο αποτέλεσμα. Η παρούσα διατριβή σκοπό έχει να μελετήσει το αν η τεστοστερόνη μπορεί να χρησιμοποιηθεί ως προγνωστικός δείκτης θετικής δεύτερης βιοψίας προστάτη σε ασθενείς υποψήφιους για επαναληπτική βιοψία. ΑΣΘΕΝΕΙΣ ΚΑΙ ΜΕΘΟΔΟΙ: Η μελέτη συμπεριέλαβε 320 άνδρες οι οποίοι υπεβλήθησαν σε βιοψία προστάτη στην ΄Β Πανεπιστημιακή Ουρολογική Κλινική του Πανεπιστημίου Αθηνών σε διάστημα οκτώ μηνών. Σε κάθε ασθενή μετρήθηκαν η ολική, η ελεύθερη και η βιοδιαθέσιμη τεστοστερόνη, το PSA (prostate specific antigen), η λευκωματίνη και η SHBG (sex hormone binding globulin) ενώ καταγράφησαν τα δεδομένα υπερηχοτομογραφικά και παθολογοανατομικά τόσο της πρώτης όσο και της δεύτερης βιοψίας. ΑΠΟΤΕΛΕΣΜΑΤΑ: Σαράντα ασθενείς (12,5%) χρειάστηκε να προβούν σε επαναληπτική βιοψία με διάγνωση HGPIN (high grade prostate intraepithelial neoplasia) σε 14 (35%) και καρκίνο προστάτη σε 12 (30%). Η στατιστική ανάλυση (μονο- και πόλυπαραγοντική) των δεδομένων έδειξε πως οι ασθενείς με καρκίνο του προστάτη είχαν αυξημένα επίπεδα συνολικής τεστοστερόνης (p=0,036) και βιοδιαθέσιμης τεστοστερόνης (p=0,005). ΣΥΜΠΕΡΑΣΜΑ: Στην παρούσα διατριβή φάνηκε πως υψηλότερα επίπεδα συνολικής και βιοδιαθέσιμης τεστοστερόνης σχετίζονται με διάγνωση καρκίνου στην επαναληπτική βιοψία. Τα αποτελέσματα της μελέτης υποδεικνύουν τον πιθανό ρόλο της ελεύθερης και της βιοδιαθέσιμης τεστοστερόνης στην πρόγνωση παρουσίας καρκίνου του προστάτη σε ασθενείς υποψήφιους για επαναληπτική βιοψία.

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Clinical significance of high grade and low grade prostate intraepithelial neoplasia

Medicni perspektivi (Medical perspectives) ◽

10.26641/2307-0404.2021.2.234640 ◽

2021 ◽

Vol 26 (2) ◽

pp. 134-140

Author(s):

M.P. Melnychuk

Keyword(s):

Clinical Significance ◽

Prostate Gland ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

High Grade ◽

Detection Rates ◽

Prostate Intraepithelial Neoplasia ◽

Prostate Biopsies ◽

The Mean

Such premalignant conditions of prostate cancer (PC) as prostate intraepithelial neoplasia (PIN) are classified between benign and malignant ones. Contemporary evidence wheather PIN develops malignancy is limited and (LGPIN) data present varied results. Morphological and clinical differencies between high (HGPIN) and low grade PIN specimens in the prostate remain unclear. Aim of the work – to determine clinical significance and progression ability of high grade and low grade prostate intraepithelial neoplasia. The results of examination of 276 patients with PIN (152 patients with high grade PIN and 134 patients with low grade PIN) were assessed comparatively. During a 3 year follow-up repeated prostate biopsies were performed with 6 months interval to detect PC. Initial and repeated multifocal transrectal prostate biopsies from 12 samples were performed under transrectal ultrasonic guidance. There were statistically significant differences in PC detection rates between HGPIN and LGPIN. Patients with HGPIN had malignization rate of 42.1% during a 3-year follow-up that was by 33.9% higher than in LGPIN patients. The spread of HGPIN lesions within prostate gland is a malignization risk factor. The mean malignization term of HGPIN is 18 months and of LGPIN – 30 months. Low and high grade PIN are gradual stages of cancerogenesis. PIN grade determines its clinical significance, while LGPIN has low malignization potential, HGPIN possesses morphological and clinical prostate characteristics similar to adenocarcinima.

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