HERV-K and HERV-H env Proteins Induce a Humoral Response in Prostate Cancer Patients

A higher expression of human endogenous retroviruses (HERVs) has been associated with several malignancies, including prostate cancer, implying a possible use as a diagnostic or prognostic cancer biomarker. For this reason, we examined the humoral response against different epitopes obtained from the envelope protein of HERV-K (HERV-K env-su19–37, HERV-K env-su109–126), HERV-H (HERV-H env-su229–241, HERV-H env387–399) and HERV-W (HERV-W env-su93–108, HERV-W env-su248–262) in the plasma of patients affected by prostate cancer (PCa), and compared to that of benign prostate hyperplasia (BPH) and a borderline group of patients with atypical small acinar proliferation (ASAP) and prostate intraepithelial neoplasia (PIN) and healthy controls. A significant antibody response was observed against HERV-K env-su109–126 (p = 0.004) and HERV-H env-su229–241 (p < 0.0001) in PCa patients compared to HCs, BPH and borderline cohorts, whilst no significance difference was found in the antibodies against HERV-W env-su93–108 and HERV-W env-su248–262 in patients with PCa. Our results provided further proof of the association between HERV-K and PCa and added new evidence about the possible involvement of HERV-H in PCa pathogenesis, highlighting their possibility of being used as biomarkers of the disease.

Clinical significance of high grade and low grade prostate intraepithelial neoplasia

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.

PROGNOSTIC SIGNIFICANCE OF MAGNETIC RESONANCE IMAGING IN PATIENTS WITH PROSTATE INTRAEPITHELIAL NEOPLASIA

The aim: To determine prognostic significance of mpMRI in prostate intraepithelial neoplasia (PIN) diagnostics. Materials and methods: The results of examination of 52 patients with PIN were assessed in mpMRI using PIRADS criteria. The total number of samples with PIN amounted 166. According to PIRADS MRI assessment of central and peripherial zones was made separately. The use of T2WI, DWI, DCE in patients with high grade and low grade PIN was studied. MRI was performed before prostate biopsy (MRI cognitive fusion biopsy). During 3-year follow-up rebiopsies were performed with prostate cancer detection. PIRADS values of PIN lesions with malignisation were compared with those without following tumor transformation. Results: There was a difference in values of PIRADS characteristics between PIN and benign prostatic tissue. The mean of PIRADS gradation in samples with PIN was 2,1. Among them 47 (28,3 %) PIN samples had gradation 3 (the presence of clinically significant cancer is equivocal), in 8 (4,8 %) cases – gradation 4 (clinically significant cancer is likely to be present). The mean of PIRADS gradation was in 24 % larger in cases with subsequent PC detection than in cases without malignisation. Conclusions: MRI parameters in PIN cases differ from normal prostate tissue. PIRADS assessment has prognostic significance of following malignisation of PIN pieces that have similar properties on MRI as prostate cancer. Further study is required to stratify all PIN patients into groups of high malignisation risk in order to perform detailed examination and treatment.

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

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.

Interobserver Variability in the Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia in a Tertiary Hospital in Northern Jordan

Prostate intraepithelial neoplasia is described as a precursor lesion to prostatic adenocarcinoma. High-grade prostate intraepithelial neoplasia (HGPIN) is classified as both grade 2 and 3 prostate intraepithelial neoplasia due to inconsistency between pathologists’ findings. In our study, we assessed the interobserver variability in the diagnosis of HGPIN among genitourinary and nongenitourinary pathologists. All cases with prostate adenocarcinoma diagnosis on needle core biopsy, radical prostatectomy, and transurethral resection of prostate (TURP) between the years 2005 and 2014 were included. In total, 191 prostate cancer cases were included: 109 needle core biopsies, 45 radical prostatectomies, and 37 TURP. All were independently reviewed by 2 urologic pathologists for the presence of HGPIN. High-grade prostate intraepithelial neoplasia was diagnosed in 65 cases (34%), among which the lesion was recognized by the reporting pathologists in 36 (55%) of the cases and was missed in 29 (45%) of the cases with a κ coefficient of 0.53. There was a moderate interobserver agreement in the diagnosis of HGPIN. Consultation with genitourinary pathologist can improve HGPIN diagnosis.

Green tea catechins for chemoprevention of prostate cancer in patients with histologically-proven HG-PIN or ASAP. Concise review and meta-analysis

A focused, single outcome meta-analysis on the protective role of extracts of green tea catechins against prostate cancer. Randomized, placebo-controlled studies enrolling patients with a histologically confirmed diagnosis of high-grade Prostate Intraepithelial Neoplasia or Atypical Small Acinar proliferation but no prostate cancer were included. Meta-analysis for binary data was performed using Mantel-Haenszel statistics, using a random-effects model. Heterogeneity was investigated by calculating the I2. Four studies matched the inclusion criteria for the review. The pooled population was 223 patients; 114 and 109 patients were randomized to catechin and placebo groups, respectively. Nine cases of prstate cancer occurred in the catechin arm (7.9%), and 24 cases were reported in the placebo arm (22%). Pooled analysis resulted in a significant reduction of cancer risk in favor of the catechin arm (risk-ratio = 0.41; 95% CI: 0.19- 0.86; I2 = 0). In conclusion, our data suggest that the intake of concentrated green tea catechin preparations may confer a significant protective effect to carriers of early neoplastic lesions in the prostate. The quality of the evidence is moderate, and additional, largescale studies are warranted to substantiate these preliminary findings.