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Prostatic Intraepithelial Neoplasia

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A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer.

Also Known As:

Intraepithelial Prostatic Neoplasia; Prostatic Intraepithelial Neoplasms; Intraepithelial Neoplasia, Prostatic; Intraepithelial Neoplasm, Prostatic; Intraepithelial Neoplasms, Prostatic; Intraepithelial Prostatic Neoplasias; Neoplasia, Intraepithelial Prostatic; Neoplasm, Prostatic Intraepithelial; Neoplasms, Prostatic Intraepithelial; Prostatic Intraepithelial Neoplasias; Prostatic Intraepithelial Neoplasm; Prostatic Neoplasia, Intraepithelial; Neoplasia, Prostatic Intraepithelial

Networked: 599 relevant articles (9 outcomes, 86 trials/studies)

Relationship Network

Disease Context: Research Results

Neoplasms: 649836
- Neoplasms by Histologic Type: 1
  - Glandular and Epithelial Neoplasms: 332
    - Carcinoma: 115405
      - Carcinoma in Situ: 1902
        Prostatic Intraepithelial Neoplasia: 599

Related Diseases

1.	Neoplasms (Cancer)
2.	Prostatic Neoplasms (Prostate Cancer)
3.	Adenocarcinoma
4.	Prostatic Hyperplasia (Benign Prostatic Hyperplasia)
5.	Carcinoma (Carcinomatosis)

Experts

1.	Montironi, Rodolfo: 21 articles (03/2013 - 06/2002)
2.	Cheng, Liang: 18 articles (02/2013 - 02/2002)
3.	Mazzucchelli, Roberta: 13 articles (02/2013 - 06/2002)
4.	Scarpelli, Marina: 10 articles (02/2013 - 06/2002)
5.	Bostwick, David G: 10 articles (10/2009 - 01/2003)
6.	Epstein, Jonathan I: 9 articles (10/2013 - 09/2002)
7.	Lopez-Beltran, Antonio: 9 articles (02/2013 - 04/2007)
8.	De Marzo, Angelo M: 8 articles (04/2013 - 09/2003)
9.	Santinelli, Alfredo: 8 articles (02/2013 - 06/2005)
10.	Zhang, Shaobo: 7 articles (05/2011 - 02/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Prostatic Intraepithelial Neoplasia:

1.	Toremifene (Fareston)FDA Link 02/10/2013 - "We evaluated the efficacy of toremifene citrate 20 mg in PCa prevention among men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy. " 06/01/2003 - "Phase IIA clinical trial to test the efficacy and safety of Toremifene in men with high-grade prostatic intraepithelial neoplasia." 03/01/2002 - "High-grade prostatic intraepithelial neoplasia was observed in animals in the placebo group, but not in animals treated with toremifene. " 09/01/2006 - "A randomized, double-blind, dose finding, placebo controlled, parallel group clinical study was done to determine the incidence of prostate cancer in men with high grade prostatic intraepithelial neoplasia treated with toremifene. " 09/01/2006 - "A total of 514 patients with high grade prostatic intraepithelial neoplasia and no evidence of prostate cancer on screening biopsy were randomized to 20, 40 or 60 mg toremifene, or placebo daily for 12 months. "
2.	Prostate-Specific Antigen (Semenogelase)IBA 11/01/1990 - "Improved performance characteristics, stability, the lesser diurnal variation, and the association of elevated prostate-specific antigen with prostatic intraepithelial neoplasia make prostate-specific antigen possibly a better candidate for early detection of this common malignancy. " 04/01/2005 - "The study inclusion criteria included prostate-specific antigen level of 10 ng/mL or greater, prostate-specific antigen velocity of 0.75 ng/mL per year or greater, or the presence of prostatic intraepithelial neoplasia and/or atypical small cell acinar proliferation on the previous biopsy. " 01/01/2004 - "The study group included 31 patients with previous biopsy results demonstrating high-grade prostatic intraepithelial neoplasia, 7 with atypia, and 62 with benign prostatic tissue but persistently elevated prostate-specific antigen levels. " 05/01/2001 - "In addition, study inclusion required high risk parameters, including prostate specific antigen (PSA) velocity greater than 0.75 ng./ml., PSA greater than 10 ng./ml. or previous prostatic intraepithelial neoplasia on biopsy, and/or atypical small cell acinar proliferation. " 11/01/2014 - "Repeat biopsy was performed in 374 of the 4,883 patients with an initial negative finding and a persistently elevated prostate-specific antigen (PSA) level, nodules or asymmetry by digital rectal examination (DRE), high-grade prostatic intraepithelial neoplasia, or atypical small acinar proliferation. "
3.	SeleniumIBA 11/01/2011 - "Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917." 08/01/2006 - "Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia." 04/01/2001 - "The second is for men with high-grade prostatic intraepithelial neoplasia; the trial will test whether selenium will prevent the development of prostatic cancer in this high-risk group. " 01/01/2001 - "The studies under way involve continued follow-up of the study cohort that generated the 1996 results and trials of selenium among men with negative biopsies, men with high-grade prostatic intraepithelial neoplasia, men with prostate cancer treated with selenium before prostatectomy, and men with prostate cancer who have chosen watchful waiting rather than active intervention. " 02/01/2004 - "These observations give strong scientific support to ongoing clinical trials testing the ability of selenium to prevent prostate cancer and the progression of high grade prostatic intraepithelial neoplasia to cancer."
4.	Finasteride (Propecia)FDA LinkGeneric 07/01/2007 - "High grade prostatic intraepithelial neoplasia alone was diagnosed in 276 men (6.0%) in the finasteride group vs 347 (7.1%) in the placebo group (RR 0.85, 95% CI 0.73-0.99, p=0.04). " 07/01/2007 - "The number of men evaluable for high grade prostatic intraepithelial neoplasia was 4,568 in the finasteride group and 4,886 in the placebo group. " 07/01/2007 - "Finasteride decreases the risk of prostatic intraepithelial neoplasia." 12/01/1996 - "Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). " 12/01/1996 - "To develop a methodology applicable to the morphologic study of the efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative precursor of prostate cancer. "
5.	Vitamin E FDA LinkGeneric 06/10/2011 - "Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium." 01/01/2013 - "Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. " 01/01/1996 - "For prostate cancer, modulation of prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. " 01/01/1997 - "Over 40 short-term clinical trials are in progress, testing the following classes of agents on precancerous lesions in the different major organ systems: antimutagens (N-acetylcysteine, oltipraz), antiproliferatives (difluoromethylornithine, dehydroepiandrosterone, selenomethionine), antioxidants (vitamin E, curcumin), anti-inflammatories (aspirin, piroxicam, ibuprofen, sulindac sulfone) and hormonally active agents (tamoxifen in breast ductal carcinoma in situ and finasteride in prostatic intraepithelial neoplasia). "
6.	DNA (Deoxyribonucleic Acid)IBA 01/01/2009 - "Prostatic intraepithelial neoplasm (PIN), a precursor lesion of PCa, has been demonstrated to contain CpG island hypermethylation, but little is known about the role of DNA hypomethylation. " 08/01/1993 - "Computerized static DNA ploidy analysis of prostatic intraepithelial neoplasia." 10/01/1990 - "The changes in nuclear morphology (karyometry) and DNA content in prostatic intraepithelial neoplasia (PIN) were analyzed on tissue sections. " 09/15/2010 - "Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. " 05/01/1994 - "Comparison of DNA ploidy in prostatic intraepithelial neoplasia and invasive carcinoma of the prostate: an image cytometric study."
7.	MucinsIBA 01/01/2007 - "Minor criteria include intraluminal wispy blue mucin, pink amorphous secretions, mitotic figures, intraluminal crystalloids, adjacent high-grade prostatic intraepithelial neoplasia, amphophilic cytoplasm and nuclear hyperchromasia. " 08/01/2000 - "Other features associated with malignancy (mitoses, blue-tinged mucin, adjacent high-grade prostatic intraepithelial neoplasia, and perineural invasion) were seen infrequently. " 12/01/1997 - "The following histologic features were identified in 54 cases: enlarged nucleoli, 54 (100%); enlarged nuclei, 45 (83%); intraluminal eosinophilic secretions, 40 (74%); infiltrative growth, 37 (68%); small acinar proliferation, 37 (68%); intraluminal basophilic mucin, 23 (42%); amphophilic cytoplasm, 18 (33%); high-grade prostatic intraepithelial neoplasia, 17 (31%); and crystalloids, 12 (22%). " 10/01/1999 - "Histologic features that were helpful in the diagnosis of cancer after radiation therapy included infiltrative growth, perineural invasion, intraluminal crystalloids, blue mucin secretions, the absence of corpora amylacea, and the presence of coexistent high-grade prostatic intraepithelial neoplasia. " 12/01/1997 - "These histologic findings included number of biopsy cores (mean 5.5), number of acini per focus of ASAP (mean 7.9), number of foci (mean one), variation in acinar size, nuclear enlargement (none, 12% of cases; mild, 45%; moderate, 33%; severe, 10%), nucleolar enlargement (none, 27%; mild, 46%; moderate, 27%), luminal mucin (39%), crystalloids (6%), focal chronic inflammation (64%), adjacent atrophy (100%), and adjacent high-grade prostatic intraepithelial neoplasia (PIN) (42%). "
8.	celecoxib (Celebrex)FDA Link 03/01/2009 - "The cyclooxygenase-2-inhibitor celecoxib has been shown to inhibit cell growth and to reduce prostatic intraepithelial neoplasia in mice. " 02/15/2006 - "Dietary supplement of celecoxib at doses of 400 ppm, 600 ppm, and 1,000 ppm are most effective against mPIN (mouse prostatic intraepithelial neoplasia) and adenocarcinoma of the prostate. " 10/01/2007 - "The rats that received celecoxib in combination with exisulind at low doses showed a significant decrease in prostatic intraepithelial neoplasia and adenocarcinomas as well as an enhanced rate of apoptosis. "
9.	Selective Estrogen Receptor Modulators (SERM)IBA 05/01/2003 - "A phase IIb/III human clinical trial is currently evaluating safety and efficacy of toremifene, a SERM, in men who have high-grade prostatic intraepithelial neoplasia."
10.	Biological Markers (Surrogate Marker)IBA 04/01/2001 - "Some of the key topics included recent advances in the state of knowledge of promising agents in the clinic based on molecular targets as well as bottlenecks in drug development for pharmaceutical sponsors; strategic modulable biomarkers that can serve as primary endpoints in phase 1/2 trials to assess preventive efficacy; high-risk cohorts with precancer (high-grade prostatic intraepithelial neoplasia) and representative clinical trial designs that are ready for immediate translation into efficient prevention trials, such as Bayesian sequential monitoring for early assessment of biologic activity and factorial designs for assessment of multiagent combinations. " 04/01/2001 - "Two candidate surrogate endpoints (SE) based on histology are high-grade prostatic intraepithelial neoplasia (HGPIN) and computer-assisted image analysis of dysplastic lesions. " 02/01/1999 - "Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses." 07/01/2015 - "Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia." 12/01/1999 - "In high-grade prostatic intraepithelial neoplasia (PIN), this alteration is present in at least 70% of cases (Brooks et al, Cancer Epidemiol Biomarkers Prev, 1998, 7:531-536). "

Therapies and Procedures

1.	Prostatectomy (Retropubic Prostatectomy) 01/01/2015 - "The expression of PSGR in paired adjacent normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and PCa were determined by immunohistochemistry on tissue microarrays constructed from 150 radical prostatectomy specimens. " 12/01/2014 - "The presence of high-grade prostatic intraepithelial neoplasia or atypia on prostate biopsy does not adversely affect prostatectomy outcomes for patients otherwise eligible for active surveillance." 01/01/2014 - "To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP). " 01/01/2014 - "Concomitant high-grade prostatic intraepithelial neoplasia is associated with good prognosis factors and oncologic outcome after radical prostatectomy." 08/01/2013 - "To evaluate whether the number of biopsies performed via transrectal ultrasound (TRUS) accurately predicts pathological parameters such as Gleason sum, prostatic intraepithelial neoplasia and perineural invasion of the final prostatectomy specimen. "
2.	Chemoprevention 01/01/2014 - "Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. " 01/01/1999 - "Reversibility of prostatic intraepithelial neoplasia: implications for chemoprevention." 01/01/1999 - "Prostatic intraepithelial neoplasia: A marker for high-risk groups and a potential target for chemoprevention." 01/01/1996 - "To evaluate the potential application of chemoprevention strategies in prostatic intraepithelial neoplasia. " 01/01/1996 - "Chemoprevention for prostatic intraepithelial neoplasia."
3.	Castration 12/01/2015 - "These studies suggest that cancer stem cells capable of tumor propagation exist at various stages of tumor progression from prostatic intraepithelial neoplasia (PIN) to advanced metastatic and castration-resistant disease. " 08/15/2006 - "In particular, we have been studying the evolution of androgen independence in Nkx3.1; Pten mutant mice, which develop prostatic intraepithelial neoplasia and adenocarcinoma as a consequence of aging, as well as androgen-independent phenotypes following castration. " 03/11/2010 - "Prostate cancer (CaP) progresses from prostatic intraepithelial neoplasia through locally invasive adenocarcinoma to castration-resistant metastatic carcinoma. " 05/01/2014 - "Protein expression was evaluated by immunohistochemistry on tissue microarrays containing samples from normal prostate (NL, n = 91), high-grade prostatic intraepithelial neoplasia (PIN, n = 61), clinically localized PCa (CLC, n = 434), PCa metastases (M, n = 28), and castration-resistant PCa (CRC, n = 49). " 01/01/2013 - "Using a preclinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by PTEN loss, we observed unprecedented deteriorating effects of androgen deprivation, in which surgical castration or MDV3100 treatment accelerated disease progression of the otherwise stable HG-PIN to invasive castration-resistant prostate cancer (CRPC). "
4.	Transplantation (Transplant Recipients) 01/01/2009 - "In our study, high-grade prostatic intraepithelial neoplasia (PIN) was found with high frequency at 8 weeks post-tissue recombination transplantation. " 05/01/2011 - "At 8-16 weeks after transplantation into immune-deficient mice, the development of lesions, histologically classified as benign prostate, prostatic intraepithelial neoplasia and adenocarcinoma, can be evaluated." 12/01/2010 - "Orthotopic transplantation of Pten/TP53 null cells derived from protospheres produced invasive Prostatic Intraepithelial Neoplasia (PIN)/adenocarcinoma, recapitulating the pathology seen in primary tumors. "
5.	Aftercare (After-Treatment) 12/01/1996 - "Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). " 10/01/1999 - "The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). "