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)

Prostate-specific antigen is a kallikrein-like serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. Prostate-specific antigen is also present in the serum and can be measured reliably by several different assays. Although the protein is prostate-specific, it is not prostate-cancer-specific. As a result, benign conditions such as benign prostatic hyperplasia, prostatitis and infarction, as well as prostatic intraepithelial neoplasia, can be associated with elevated serum levels of prostate-specific antigen. Approximately 25% of men with benign prostatic hyperplasia have an elevated serum value of prostate-specific antigen, whereas 35% to 40% of patients with organ-confined prostate cancer have a level within the reference range. Prostate-specific antigen can identify some cancers not detectable by digital rectal examination; alternatively, this examination can identify cancers not detectable from the serum prostate-specific antigen concentration. Thus, the most complete evaluation of the prostate gland is achieved when both the prostate-specific antigen value and the digital rectal examination are used. The density and the rate of change of serum prostate-specific antigen are new concepts to improve the ability of prostate-specific antigen to detect early prostate cancer. Preliminary results are encouraging, but additional studies are required to determine the true usefulness of these new variables. Thus, in 1992, determination of the prostate-specific antigen value is a valuable new tool for the practicing physician and will be instrumental in our campaign to diagnose clinically significant prostate cancer at an early, curable stage.
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PMID:Prostate-specific antigen and diagnosing early malignancies of the prostate. 128 95

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

Premalignant lesions of the prostate fall into two categories. The first category includes formation of new, usually small, glands which are either abnormally distributed or show minimal nuclear atypia or both. Morphologically, this lesion presents the differential diagnostic alternatives of micro-acinar hyperplasia on the one hand and a low grade micro-acinar cancer on the other. If the presence or absence of nuclear anaplasia or acinar dispersion (i.e., stromal invasion) raises any degree of doubt, atypical glands are diagnosed. This is the category that is considered by some to be the precursor of well differentiated prostate cancer. The second category is prostatic intraepithelial neoplasia (PIN). We have defined PIN as an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. We consider PIN as essentially carcinoma in situ. The lesion designated by some as PIN 1 is classified by us as atypical hyperplasia.
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PMID:Prostatic intraepithelial neoplasia (PIN): morphological clinical significance. 137 79

A total of 666 patients with symptoms of urinary outflow obstruction underwent assessment of the patients 64 had a palpable abnormality suggestive of cancer (stages T1 to T4, or B to C). In the remainder the prostate was either palpably normal, firm or enlarged by benign prostatic hypertrophy. All 64 patients with a palpable abnormality and 162 of 602 with normal rectal examination findings had a hypoechoic area on transrectal ultrasound. Biopsy of the ultrasonic abnormality was done in 148 men by the transperineal route with linear array ultrasound guidance and in 78 by the transrectal route with a mechanical sector scanner in the sagittal plane. Of the 64 patients with a nodular prostate 34 (53%) had cancer (31% of those with stages T1 and 2, 83% with stage T3 and 100% with stage T4 disease). In 14% of the patients with stages T1 and T2 cancer the biopsy showed prostatic intraepithelial neoplasia grade 3. Of the 162 patients with a palpably normal prostate who underwent ultrasound-guided biopsy 11 (6.7%) had cancer and 6 (3.7%) had grade 3 prostatic intraepithelial neoplasia detected in the biopsy material. Patients with stages T1 to T2 cancer and those with ultrasound-diagnosed impalpable cancer were not significantly different with respect to patient age (67 versus 70 years), cancer size (3.0 +/- 1.6 versus 3.9 +/- 2.5 cm.2) or Gleason score (5.4 +/- 1.2 versus 6.5 +/- 0.9). The results demonstrate that ultrasound guidance improves the yield of prostate needle biopsy. Furthermore, it is suggested that prostate cancer found by ultrasound alone is not different from early palpable disease and should be treated in the same manner.
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PMID:The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. 168 55

Acid phosphatase and prostate-specific antigen are extremely useful markers for the management of patients with prostatic carcinoma. Prostatic acid phosphatase, because of its relatively low sensitivity and specificity, as well as analyte instability and diurnal variability, is unsuitable for prostate cancer screening. 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. Further investigations in this area are clearly indicated before we can recommend screening with prostate-specific antigen.
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PMID:Laboratory studies for the detection of carcinoma of the prostate. 169 41

PSA is a kallikrein-like, serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. PSA is also present in the serum and can be measured reliably by either a monoclonal immunoradiometric assay or a polyclonal radioimmunoassay. The calculated half-life of serum PSA ranges from 2.2 to 3.2 days and the metabolic clearance rate of this tumor marker follows first-order kinetics. Digital rectal examination, cystoscopic examination and prostate biopsy all can cause spurious elevations of the serum PSA concentration. Conditions such as bacterial prostatitis and acute urinary retention also can falsely elevate the serum PSA level. Because approximately 25% of the patients with BPH only will have an elevated serum PSA concentration and BPH tissue contributes to this PSA value in a variable manner from patient to patient, it is unlikely that PSA by itself will become an effective screening tool for the early diagnosis of prostate cancer. However, if combined with digital rectal examination and/or transrectal ultrasound it may become a vital part of any early detection program. Prostatic intraepithelial neoplasia also may be associated with moderately elevated serum PSA levels. Although there is a direct correlation between the serum PSA concentration and clinical stage, PSA is not sufficiently reliable to determine the clinical stage on an individual basis. This finding also applies to pathological stage. As a result, the preoperative serum PSA concentration cannot be used to decide whether to recommend radical prostatectomy for potential cure. Low preoperative serum PSA concentrations in patients with previously untreated prostate cancers are predictive of a negative bone scan. Thus, in these select patients a staging bone scintigram may not be necessary. With respect to monitoring patients after definitive therapy, PSA is an exquisitely sensitive tumor marker. Irrespective of the treatment modality (radical prostatectomy, radiation therapy or antiandrogen treatment), PSA reflects accurately the tumor status of the patient and is prognostic of eventual outcome; this tumor marker is capable of predicting tumor recurrence months before its detection by any other method. PSA is also a most useful immunocytochemical marker. Its sensitivity and specificity to identify tissue of prostatic origin approach 100%. When compared to PAP, PSA is a more precise and meaningful marker in all clinical situations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. 170 89

No definite relationship can be demonstrated between benign prostatic hyperplasia (BPH) and prostatic cancer on the basis of various anatomic and morphologic features. However, interesting recent observations suggest a link between BPH and prostate cancer. Clinically, the simultaneous presence of benign and malignant disease is observed quite often, and this coexistence is bound to increase with the age of patients. Possible intermediate forms between BPH and early cancer have been investigated. Two premalignant lesions have been identified: atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia.
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PMID:Is there a relationship between benign prostatic hyperplasia and prostatic cancer? 172 59

To determine the characteristics of transition zone and peripheral zone prostate cancer, we examined a series of 42 stage A and 54 stage B radical prostatectomy specimens with particular attention to the number of separate foci of cancer, zone of origin, volume and grade of each focus, and presence of severe intraductal dysplasia (high grade prostatic intraepithelial neoplasia), extra-capsular extension and seminal vesicle invasion associated with cancer in each zone. We found that there were fundamental differences between transition zone and peripheral zone cancers, and that the features that characterize these tumors were apparent in stages A and B disease. Although the total tumor burden was similar in stages A (3.98 cc) and B (4.56 cc) disease, stage A cancer tended to be multifocal (3.1 tumors per prostate) and more diffuse. While 81% of stage A prostate specimens contained a tumor of transition zone origin and 93% had cancer of peripheral zone origin, transurethral resection of the prostate sampled a transition zone cancer in 77% and a peripheral zone cancer in 31% (8% had both types). Stage B cancer tended to be more focal (2.3 cancers per prostate). All stage B prostate specimens contained a peripheral zone cancer and 43% had a transition zone cancer as well. In only 1 stage B cancer patient was the transition zone tumor the palpable or index cancer. In stages A and B disease, peripheral zone tumors were less well differentiated (median Gleason sum 6 and 7) than transition zone tumors (5 and 5, respectively) and more likely to extend through the capsule (44% versus 11%). Seminal vesicle invasion arose from 19% of the peripheral zone but none of the transition zone cancers. Peripheral zone tumors were almost always (93%) associated with high grade prostatic intraepithelial neoplasia, while none of the transition zone cancers was so associated. For peripheral zone disease there was a moderate correlation between volume and grade (tau = 0.46, p less than 0.001) so that the larger the tumor the higher the Gleason sum but within transition zone disease this correlation was poor (tau = 0.23) and not statistically significant (p greater than 0.05). Extracapsular extension occurred at a smaller volume with peripheral zone cancer (mean 3.86, minimum 0.06 cc) than transition zone cancer (mean 4.98, minimum 0.39 cc). Cancer that arises in the transition zone appears to have a different histogenesis, is associated with more favorable pathological features and may have less malignant potential than tumors that arise in the peripheral zone.
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PMID:A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. 189 23

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

New as well as standard techniques for the detection and diagnosis of early prostate cancer have been described. These include the use of digital rectal examination, prostate-specific antigen, transrectal ultrasound, prostatic acid phosphatase, the Biopty gun, and cell ploidy, as well as the diagnosis of premalignant lesions of the prostate, such as prostatic dysplasia or, more appropriately, prostatic intraepithelial neoplasia. All of these innovations may enhance our ability to diagnose and follow patients with early prostate cancer. Full documentation and evaluation of long-term (15 to 20 years) follow-up, however, are needed to determine whether these new techniques will make a difference in the ultimate morbidity and mortality of prostate cancer in the United States. In the meantime, however, the use of these new diagnostic tools should not be avoided. We must advance with technology, and as the technologies grow and develop we should increase our understanding about the utility of each of these new tests and combine them with the older standard tests that have served us well for many years.
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PMID:The role of new modalities in the early detection and diagnosis of prostate cancer. 248 15


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