Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen ablation using hormonal manipulation is used extensively in metastatic prostate cancer; however, its use in localized disease combined with surgical extirpation of the gland has not been thoroughly and systematically investigated. The rationale for neoadjuvant therapy stems from the demonstrated effectiveness of androgen ablative therapy in metastatic disease and the high rate of "positive" surgical margins, especially in patients with Stage B2 disease. In addition, the essentially anecdotal clinical report of Scott and Boyd [1], using endocrine therapy plus radical prostatectomy in patients with Stage C disease, gives 15 year survival results comparable to those obtained by Jewett [2] in Stage 1 patients treated by radical prostatectomy. Finally, experimental observations in the androgen-sensitive mammary tumor (Shionogi) lend support to the concept of neoadjuvant hormonal manipulation. A pilot study of neoadjuvant endocrine therapy in 55 patients treated at Memorial Sloan-Kettering Cancer Center with 3 months of diethylstilbestrol (DES) (3 mg/day) prior to radical prostatectomy indicates marked reductions in prostate-specific antigen (PSA), although persistent evidence of adverse local tumor features was common. Some patients, however, exhibited evidence of significant downstaging. Whether or not any alteration in disease progression will accrue from demonstrated local downstaging is, of course, uncertain. However, clinical and laboratory effects of such treatment may provide a means for correlation with subsequent tumor behavior, and may prove useful in treatment decisions. Additionally, a decrease in the number of foci of grade 3 prostatic intraepithelial neoplasia (PIN-3) was noted in a small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neoadjuvant hormonal manipulation: a strategy for chemoprevention trials. 128 66

Prostatic intra-epithelial neoplasia (PIN, or intraductal dysplasia) is considered a precursor of invasive carcinoma, characterized by proliferation and anaplasia of cells lining prostatic ducts and acini. The highest grade of PIN, Grade 3, is thought to represent carcinoma in situ. To quantitate the degree of disruption of the basal cell layer in human prostatic ducts and acini as a potential marker of early invasion in PIN, a monoclonal antibody to keratin proteins of 49, 51, 57, and 66 kd which selectively labels the prostatic basal cell layer was used. A total of 1093 acini with PIN were identified in 14 cases with invasive carcinoma. Tumor cells consistently failed to be decorated with this antibody. The frequency of disruption of the basal cell layer increased with increasing grades of PIN, with disruption present in 0.7% of cases of PIN 1, 15% of cases of PIN 2, and 56% of cases of PIN 3. The amount of disruption of the basal cell layer also increased with increasing grades of PIN, with loss of more than one third of the basal layer in 52% of foci of PIN 3 compared with less than 2% in lower grades of PIN. Disruption of the basal layer was more common in acini adjacent to invasive carcinoma than in distant acini. These findings suggest that early invasion in prostate cancer is characterized by disruption of the basal layer, and that invasion occurs commonly in association with foci of high-grade prostatic intra-epithelial neoplasia.
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PMID:Prostatic intra-epithelial neoplasia and early invasion in prostate cancer. 243 20

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

Prostate specific antigen has become an important adjunct to the digital rectal examination in screening for prostate cancer. The clinician should be familiar with interpretation of this test. Many men with BPH have elevated serum PSA concentrations; however, the majority of these men will have other pathologic processes such as occult cancer, PIN, or acute inflammation that may account for the elevations in serum PSA. Certainly, serial increases in serum PSA should increase concern that occult carcinoma is present. Patients with PIN may also have elevated PSA concentrations. When PIN is associated with elevated PSA, a high incidence of invasive carcinoma is noted on subsequent biopsy. Further investigation into the associations will further refine the clinical utility of this powerful tumor marker.
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PMID:PSA in benign prostatic hyperplasia and prostatic intraepithelial neoplasia. 750 69

The topic of this investigation was to compare precancerous lesions of the prostate (prostatic intraepithelial neoplasia -PIN- and atypical hyperplasia -AH-) and invasive carcinomas concerning DNA ploidy (image cytometry/ICM) and morphologically feasible chromosomal aberrations (interphase cytogenetics/NISH). The aim was to find clues to formal pathogenesis of prostatic cancer. Prostatic tissue of 76 patients (76 areas with carcinoma, 71 with PIN, and 12 with AH) was examined by means of ICM. In 44 cases of coincidental PIN and carcinoma, the gradings of PIN and carcinoma correlated. C-values, 2,5c-exceeding-rate, and aneuploidy rate turned out to increase in PIN and carcinoma with increasing grading (P < 0.01). In some of these cases NISH was carried out in serial sections by applying centromer-(X,Y,1,7,8,10,17,18) and telomer-(1p) specific DNA probes. The result of this approach was an increase in the number of chromosomal aberrations and chromosomes involved correlating with the grading. Our conclusion is that PIN 1 could be regarded as the precancerous lesion mainly to higher differentiated carcinomas, whereas PIN 2 and 3 should be considered a preneoplastic condition mainly of moderately and low differentiated carcinomas.
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PMID:[Prostate cancers and potential precancerous conditions: DNA cytometric investigations and interphase cytogenetics]. 751 9

The necessity of early detection of prostate cancer renewed interest regarding putative premalignant lesions in the tumorigenesis of the prostate. Prostatic intraepithelial neoplasia (PIN) is one potential precursor for prostatic adenocarcinoma. The term PIN has been adopted to replace a wide range of synonyms in the literature that describe potential precursors. PIN is an intraluminal proliferation of the secretory cells lining architecturally benign prostatic ducts and acini that exhibit cytologic atypia. In this review, we discuss the histologic features, the differential diagnosis, the evidence that PIN is a precursor of prostatic carcinoma, and the clinical significance of PIN.
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PMID:Prostatic intraepithelial neoplasia: a potential precursor lesion of prostatic adenocarcinoma. 766 Jun 73

Prostatic cancer is the second most frequent cancer in men in industrialised countries. The histological analysis of its initial development demonstrates the existence of precancerous lesions, PIN. The initial presence of several different cell populations accounts for the development of contingents of hormone-sensitive and hormone-resistant cells. The presence of numerous neuroendocrine cells appears to be a factor of poor prognosis. Hormones are intimately involved in the development of prostatic cancer and are an integral part of its treatment. Progress in molecular biology has furthered out knowledge of this disease. In particular, growth factors such as EGF and FGF are particularly involved and are starting to have a clinical application. The oncogene and anti-oncogene system is currently being explored (particularly p53 abd BCL 2). They are the basis for carcinogenesis and analysis of these factors will allow a better approach to the mechanisms of tumour induction and development.
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PMID:[Cancer of the prostate. 2. Physiology and cellular development]. 771 57

Chemoprevention trials in prostate cancer would involve excessively long follow-up if conventional endpoints of efficacy are used. Prostatic intraepithelial neoplasia (PIN) may be an appropriate surrogate endpoint for monitoring outcome during prostate cancer chemoprevention studies. To address the question of whether PIN could be stratified into "stable" PIN and PIN likely to progress to invasive cancer, we selected patients with a single focus of peripheral zone cancer with ipsilateral and contralateral high-grade PIN. Sixteen patients met these criteria from a series of 550 patients treated by radical prostatectomy. We examined the rate of apoptosis in PIN and prostate cancer tissues by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on hematoxylin and eosin stained histological sections. Significant differences (ANOVA: p < 0.05) were detected between foci of prostatic intraepithelial neoplasia contralateral to the cancer and the cancer itself. There was no difference in the apoptotic index between a given cancer and a focus of PIN ipsilateral to the tumor in the same section. However, the range of apoptotic indices overlapped in all categories. Apoptotic indices appear to parallel the biological activity of PIN and malignant prostatic tissue, but may be of little benefit when used alone in monitoring the outcome of chemopreventive therapy in an individual patient.
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PMID:Apoptotic index as a biomarker in prostatic intraepithelial neoplasia (PIN) and prostate cancer. 782 93

Prostatic intraepithelial neoplasia (PIN) is regarded as the most important premalignant lesion of prostatic epithelium. The aim of this investigation was to find clues to formal pathogenesis of prostatic cancer. For this purpose DNA ploidy (determined by means of image cytometry [ICM] using 4-microns-thick Feulgen-stained paraffin sections) of PIN and invasive carcinoma was compared. Prostatic tissue of 72 patients (mean age, 67.5 years; 82 areas with carcinoma and 71 areas with PIN) was examined. In 44 cases PIN and carcinoma were coexistent in the same prostates, the PIN grade being high in 77% of these cases (P < .05). In higher-grade PIN and higher-grade carcinoma the c-values, 2.5c-exceeding-rate, and aneuploidy rate increased (P < .01). Carcinomas associated with diploid PIN (either low or high grade) showed diploidy and aneuploidy in an equal number of cases, whereas 70% of aneuploid PIN cases (all high grade) were associated with aneuploid invasive carcinomas (P < .01). Conversely, in 71% of the cases with aneuploid carcinoma the coexistent PIN (either low or high grade) was diploid. Our findings show that aneuploidy can be acquired at a preinvasive stage of carcinogenesis in the prostate and suggest that aneuploid high-grade PIN might be regarded as a precursor of some but not all aneuploid prostatic carcinomas. Image cytometry analysis seems to be a promising method for further subclassification of high-grade PIN lesions into groups with putatively lower or higher risk. However, further investigation is necessary to confirm the clinical importance of these results.
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PMID:Comparison of DNA ploidy in prostatic intraepithelial neoplasia and invasive carcinoma of the prostate: an image cytometric study. 820 Jun 45

The participants agreed that high grade prostatic intraepithelial neoplasia was the most likely precursor of prostate cancer. Consensus was reached regarding grading, suggesting that PIN be classified as low grade and high grade, noting that high grade PIN is the clinically significant end of the morphologic continuum. Grade 1 PIN is now considered low grade, and grades 2 and 3 are considered high grade. All participants agreed that urologists should be informed when high grade PIN is identified in isolation in tissue specimens, but consensus was not reached regarding the value of reporting low grade PIN. No therapy was recommended for patients with high grade PIN, although repeat biopsy and follow-up is of value. No consensus was reached regarding the biologic potential of the lesion known as atypical adenomatous hyperplasia. Further investigation is needed to determine the diagnostic utility of this finding in prostatic specimens.
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PMID:Prostatic intraepithelial neoplasia and the origins of prostatic carcinoma. 860 58


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