Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600139 (Prostate Cancer)
 4,540 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PSA represents a major advance in our tumor marker armamentarium. PIN fulfills the majority of requirements for a premalignant change. If we could determine a subset of individuals with PIN, an enriched population on which to base screening studies would emerge. In this regard the observation that PIN may be associated with elevation of the serum PSA is particularly intriguing. Considerable interest exists for early detection of prostate cancer. The high morbidity and mortality associated with this tumor coupled with the late stage at presentation by conventional means underscore the justification for such enthusiasm. However, the wisdom of screening for a cancer for which the mortality is far less than the histologic incidence remains to be proven. In the final analysis, the question is not whether we can detect more carcinoma, but rather whether we can significantly decrease patient morbidity and mortality. Until prospective randomized clinical trials demonstrate the effectiveness of early detection programs for carcinoma of the prostate, it is difficult to recommend such screening to the general public.
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PMID:Prostate-specific antigen and premalignant change: implications for early detection. 248 17

Prostatic intraepithelial neoplasia (PIN) is a putative premalignant lesion of the prostate gland. PIN has been demonstrated to share morphologic and phenotypic similarities to invasive carcinoma of the prostate. In addition, PIN is spatially related to invasive carcinoma and occurs with greater frequency in men whose prostates harbor carcinoma. Prostate-specific antigen (PSA) is a glycoprotein produced by the prostatic epithelium. For PSA to be detected in the serum, it must traverse several tissue layers to reach the circulatory system. PSA levels associated with PIN are intermediate between those of benign and malignant prostate tissue. Spatially associated occult carcinoma, disruption of the basal cell layer, and increased vascularity may account for elevated PSA values in PIN.
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PMID:Prostatic intraepithelial neoplasia and prostate-specific antigen. 750 83

Prostatic intraepithelial neoplasia (PIN) has been postulated to be the main precursor of invasive carcinoma of the prostate (IC). The occurrence, distribution and volumes of PIN and IC in addition to grade were studied in 54 patients who underwent total prostatectomy because of localised IC (T0d-T2 NO MO). PIN always occurred multifocally, localised generally in the peripheral zone (PZ) and was found in all cases. PIN 1 was the most common grade, PIN 3 the least. PIN 3 occurred exclusively in the PZ, in the vicinity of or intermingled with high grade IC. PIN and IC grades were usually concordant. The relative volumes of IC and PIN showed an inverse relationship, i.e. at small IC + PIN volumes PIN dominated, whereas at large IC + PIN volumes both relative and absolute PIN volumes were lower. Furthermore, with increasing PIN grade a tendency towards an increase in tumour volume, Gleason score and frequency of disruption of the basal cell layer was observed. These findings indicate progression from PIN to IC. DNA ploidy of PIN areas was determined by means of flow cytometry. Areas containing PIN 1, 2 or 3 were sampled (1 plug/ml of PIN). All foci displayed only diploid DNA profiles regardless of PIN volume and grade, even with coexistent IC displaying heterogeneous DNA patterns. Our results support the claim that low and medium grade prostatic carcinoma arises from near-diploid PIN stemlines and may progress into heterogeneous tumours containing non-diploid stemlines.
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PMID:Prostatic intraepithelial neoplasia and invasive carcinoma in total prostatectomy specimens: distribution, volumes and DNA ploidy. 840 24

High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor proliferation of peripheral zone, moderately to poorly differentiated prostatic adenocarcinomas. The usual cell type of the epithelial lining of HGPIN is a glandular epithelial cell with characteristic nuclear abnormalities. Here we report nine cases of unusual types of HGPIN, including three cases of signet-ring cell HGPIN, one case of small cell neuroendocrine HGPIN, and five cases of HGPIN with distinctive mucinous features. The three examples of signet-ring cell PIN were all associated with an invasive primary signet-ring cell carcinoma of the prostate. The HGPIN assumed a classical tufted and micropapillary architectural growth pattern, with the constituent cells exhibiting a morphologic appearance identical to that of the invasive signet-ring cells. The intraepithelial and invasive signet-ring cells were mucin negative and were immunoreactive for prostate-specific antigen (PSA). A fourth case displayed a mixed intraepithelial glandular-small cell neoplastic proliferation, where intraepithelial small cells were histologically identical to surrounding invasive small cell carcinoma cells. The small cell HGPIN and invasive small cell carcinoma cells were positive for the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase. In five cases, mucinous distension of HGPIN glands, producing a flat pattern of the epithelial lining layer, comprised the third unusual pattern of HGPIN. These blue mucinous secretions were readily detected by hematoxylin and eosin staining and were composed of both neutral (periodic acid-Schiff-positive) and acidic (alcian blue-positive) mucins. Herein we document the existence of an intraepithelial proliferation of neoplastic cell types-small cell neuroendocrine and signet-ring cell-that are usually considered as stromal-invasive cells in the prostate. The presence of these rare prostatic cell types in both HGPIN and invasive carcinoma provides further support for a close relationship between HGPIN and invasive carcinoma of the prostate. All three unusual types of HGPIN-signet-ring cell, small cell neuroendocrine, and mucinous-are important to diagnostically recognize because of the strength of association of HGPIN with invasive carcinoma.
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PMID:Unusual histologic types of high-grade prostatic intraepithelial neoplasia. 933 Dec 95

A variety of small acinar lesions of the prostate may mimick prostate cancer. In the central and transition zone of the prostate atypical adenomatous hyperplasia (AAH) has to be differentiated from low grade carcinoma (Gleason score 2-6). In the dorso-peripheral zone high grade PIN (prostatic intraepithelial neoplasie) and ASAP (atypical small acinar proliferations) represent the most important mimicers of carcinoma. High grade PIN has to be differentiated from intraductal carcinoma, ASAP on the other hand may mimic low grade carcinoma. The significance of basal cell type cytokeratin immunhistochemistry (IHC) in the differentiation between ASAP and low grade carcinoma of the prostate is assessed by additional MIB-1 IHC. The status of the basal cell layer in ASAP was shown to be variable (complete, fragmented and partial loss). Independently from the status of the basal cell layer the mean MIB-1 proliferation index of ASAP was significantly higher than of clearly benign lesions and did not differ from that of low grade carcinoma. Taking into account the high detection rate of carcinoma in repeat biopsies, close clinical follow up of patients with ASAP should be recommended.
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PMID:[Suspicious acinar proliferations of the prostate]. 1071 7

Prostatic intraepithelial neoplasia (PIN) is composed of dysplastic cells with a luminal cell phenotype, expressing the androgen receptor as well as prostate-specific antigen. PIN is characterized by progressive abnormalities of phenotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of carcinogenesis. High-grade PIN is considered the most likely precursor of prostatic carcinoma, according to virtually all available evidence. Androgen deprivation decreases the prevalence and extent of PIN and the degree of capillary vascularization (e.g., angiogenesis) in the surrounding stroma via suppression of vascular endothelial growth factor production. Prostatic carcinoma is also likely to arise from precursor lesions other than high-grade PIN such as low-grade PIN, atypical adenomatous hyperplasia, malignancy-associated foci, and atrophy.
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PMID:Precancerous lesions and conditions of the prostate: from morphological and biological characterization to chemoprevention. 1209 42

High Grade Prostatic Intraepithelial Neoplasia (HGPIN) has been recognized as the most likely precursor of invasive carcinoma of the prostate. Close surveillance and follow-up are indicated if subsequent procedures fail to identify carcinoma. There is still considerable controversy about the natural history of high grade PIN and most authors agree that its identification should not influence or dictate therapeutic decisions. We performed a prophylactic radical prostatectomy in such a case which has not been reported in the world literature.
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PMID:Radical prostatectomy for high grade prostatic intraepithelial neoplasia. 1245 20

Because prostate cancer has a long latency and high incidence, it is a good target for chemoprevention by agents such as retinoids, antiandrogens, antiestrogens, and vitamin D analogs. Phase II chemoprevention trials are frequently conducted on cohorts of patients with previous cancers or premalignant lesions who are scheduled for prostate cancer surgery; such trials are currently in progress with several agents. Prostatic intraepithelial neoplasia (PIN) can be used as a surrogate endpoint biomarker for prostate cancer incidence. Studies of men with high-grade PIN (HGPIN) are particularly useful in that they require a much smaller cohort of 200-400 patients instead of the 18 000 patients required for typical Phase III trials. Even with a smaller sample size, statistically significant evidence of cancer prevention is achieved due to the high probability of HGPIN progressing to cancer (35-55%). A Bayesian sequential monitoring system allows interim analysis of biomarker modulation as early as the completion of 30 patients. Putting all these strategies together will help inhibit, delay, or modulate the natural history of prostate carcinogenesis.
Prostate Cancer Prostatic Dis 1999 Jan
PMID:Strategies for chemoprevention of prostate cancer. 1249 54

Endoglin is a nonsignaling receptor for transforming growth factor that contributes to the action of this growth factor in diverse cell types. It may also exhibit a function of its own. Endoglin levels vary with disease states and is a marker of new blood vessels. We studied endoglin expression in whole-mount prostate sections from 64 patients with localized prostate cancer, assessing reactivity in the epithelium, the stroma, and blood vessels. Cells in normal/benign acini were negative but significantly immunoreactive (P<0.001) in both prostatic intraepithelial neoplasia (PIN; 52% of cases) and malignant areas (77% of cases). In tumors, this involved less than 25% of malignant cells in 59% of specimens. The endoglin-stained stroma was detected mainly in areas surrounding PIN acini and tumors. Endoglin antibodies detected more microvessels than von Willebrand Factor antibodies in all prostatic areas (P<0.01). In addition, the number of microvessels increased with the development of cancer and correlated with Gleason score (P<0.01). Changes in endoglin expression in PIN and malignant cells, the surrounding stroma, and related blood vessels, suggest that endoglin function may be altered in prostate cancer.
Prostate Cancer Prostatic Dis 2004
PMID:Whole-mount prostate sections reveal differential endoglin expression in stromal, epithelial, and endothelial cells with the development of prostate cancer. 1517 61

Early diagnosis of prostate cancer holds tremendous promise for the effective therapy and impact on survival of prostate cancer patients. High-grade prostatic intraepithelial neoplasia (HGPIN) is generally accepted as a lesion indicative of a late pathological event in the premalignant changes leading to full development of prostate cancer. This review seeks to identify specific molecular events that may be linked directly to the molecular transition from benign prostate epithelial cells to prostate carcinoma. HGPIN is pathologically detected in a limited group of men undergoing prostate cancer screening for an elevated serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE). Loss of apoptotic control provides a molecular basis for the contribution of specific defective steps in the pathway towards development and progression of prostate cancer. Comparative dissection of the apoptosis status and expression profile of key apoptotic regulators among foci of highly proliferative benign prostatic epithelium, PIN and prostate adenocarcinoma from adjacent areas of the same gland revealed a novel insight into the dysfunctional apoptosis events contributing to prostate carcinogenesis. The sequential and notable loss of the three critical signaling components of the apoptotic action of transforming growth factor-beta (TGF-beta), in the prostate, that is, the transmembrane receptor II (TbetaRII), the key cell cycle inhibitor p27(Kip1), as well as the protagonist downstream effector of the TGF-beta signaling mechanism, Smad4, points to their potential value to 'faithfully' characterize HGPIN, as a premalignant prostate lesion. Recent evidence on the molecular changes in apoptosis regulators contributing to HGPIN and their role as molecular markers of disease onset, as well as candidates for therapeutic targeting/chemoprevention of prostate cancer in its early stages will be discussed.
Prostate Cancer Prostatic Dis 2005
PMID:Apoptotic regulators in prostatic intraepithelial neoplasia (PIN): value in prostate cancer detection and prevention. 1547 76


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