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)

Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10 normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin-embedded serial sections using a panel of nine anti-keratin monoclonal antibodies (mAbs); 34 beta E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35 beta H11, CK5, M20, and one of anti-actin mAb, HHF35. In normal/hyperplastic prostates, RPN1162, 35 beta H11, CK5 and M20 stained luminal cells without staining basal cells, and 34 beta E12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of the mAbs labelling luminal cells stained cancer cells with variable frequencies in a manner unrelated to the grade of tumour differentiation. Of the prostate cancer cases 92% were scored positive with M20, 84% with 35 beta H11, 80% with CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell-specific keratins labelled with 34 beta E12, CK8.12 and 312C8-1 were totally negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic or neoplastic epithelial cells of the prostate. Our findings indicate that the major part of the cells of prostatic adenocarcinomas have keratin phenotypes similar to luminal cells but not basal cells, and that no myoepithelial differentiation can be detected in epithelial cell of the prostate. Thus, mAbs for keratins facilitate the identification of epithelial cell phenotypes in normal, benign and malignant conditions of the prostate.
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PMID:Keratin profiles in normal/hyperplastic prostates and prostate carcinoma. 138 Nov 29

Monoclonal antibodies (MAbs) to specific keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to keratin 7 (RCK 105, OV-TL 12/30) and keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The keratin 18 MAbs distinguished adenocarcinomas (which are keratin 18 positive) from most squamous cell carcinomas (which are generally keratin 18 negative). The MAbs to keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (keratin 7 positive) and carcinomas of the gastrointestinal tract (keratin 7 negative), or between transitional cell carcinomas (keratin 7 positive) and prostate cancer (keratin 7 negative). In general, malignancies showed the expected keratin reactivity pattern as concluded from the keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same keratin protein were observed, both in the normal and malignant human tissues, indicating that specific keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and cytopathology, in which they add to a more refined diagnosis of (adeno)carcinomas.
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PMID:Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas. 169 May 12

The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.
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PMID:A glycosaminoglycan inhibitor of thrombin: a new mechanism for abnormal hemostatic assays in cancer. 189 11

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

Primary cell cultures were established from tissue specimens obtained from patients undergoing transurethral resection of the prostate. Cytogenetic analysis of these cultures revealed a normal male chromosomal complement from one and a 45,X karyotype from another patient with benign prostatic hyperplasia. In addition, a normal male chromosomal complement was observed from a moderately differentiated prostatic carcinoma, and a grossly abnormal karyotype was observed from a poorly differentiated adenocarcinoma of the prostate. This latter specimen contained a modal chromosome number of 84 with several consistent marker chromosomes including homogeneous staining regions and double minutes, and no normal chromosomes 3, 5, 10, 15 or Y. Primary prostatic cell cultures exhibit epithelial-specific keratin intermediate filament proteins, and, in conjunction with cytogenetic analysis, provide a model for the study of human prostate cancer.
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PMID:Cytogenetic analysis of four primary prostatic cultures. 246 37

The purpose of this study is to demonstrate the localization and distribution of keratin-positive cells (KPC) in the various pathological types of prostatic cancer, and to investigate the correlation between the basal cell and KPC. The localization of keratin was immunohistochemically investigated in 20 benign prostatic hyperplasia (BPH) and 33 human prostatic adenocarcinomas by the indirect immunoperoxidase technique, using anti human keratin rabbit serum on frozen sections. In BPH, strongly positive staining for keratin was detected in the cytoplasm of basal cells. Glandular epithelial cells were positive. In the cancer sections, no KPC was observed in all 6 cases of the large acinar type, all 10 cases of the small acinar type and all 12 cases of the column and cord type. On the other hand, KPC remained around the cancer cell populations in all 10 cases of the cribriform type. In the fused gland type, KPC was localized in 3 of 9 cases and in the medullary type 3 of 7 cases. If KPC was regarded as the marker of the basal cell as shown in BPH, it would be speculated that the absence of KPC occurred in some type of prostatic cancer showed the disappearance of basal cell. That is, KPC could not be detected in large acinar, small acinar and column and cord type, while KPC remained completely or partially in the cribriform, fused gland and medullary type. These histochemical alteration would suggest the different degree of malignancy in the various histological type of prostatic cancer.
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PMID:[Immunohistochemical study of keratin-positive cells in human prostatic cancer]. 248 62

To evaluate if there is any consistent relationship between the expression of intermediate filament proteins (IFP), particularly keratins, and the degree of malignancy of prostatic cancer cells, a series of nine Dunning rat prostatic cancer sublines that span the entire spectrum of progression of prostatic cancer were studied immunocytochemically by the use of a variety of antibodies specific for keratins, vimentin, or desmin. For the keratin studies, monoclonal antibodies with either a general reactivity to several keratins or highly specific for either luminal or basal epithelial cells of the normal rat prostate were used. By use of an antibody specific for luminal cell keratin 18, the luminal tumor cells of the well-differentiated, slow-growing H and HI-S sublines were positively stained. In most of the sublines with a more advanced state of progression (i.e., the moderately differentiated, moderately fast growing HI-M; the poorly differentiated, faster growing HI-F; and the anaplastic, very fast growing AT-1, AT-2, and MAT-Lu tumors), however, no expression of keratin specific for luminal cells was detected. In addition, several of the most advanced sublines (i.e., AT-1, AT-2, and MAT-Lu) were negative using any of the keratin antibodies. In contrast, several of the other sublines with the most advanced degree of progression (i.e., the anaplastic, very fast growing MAT-LyLu tumor derived from the AT-1 subline; and the anaplastic, very fast growing AT-3 tumor, derived from the HI-F subline), however, were positively stained with the keratin antibody specific for the luminal cells. By use of the keratin antibody specific for the basal cells of the normal rat prostate, the basal tumor cells of the well-differentiated slow-growing H and HI-S tumor were positively stained. This positive staining for basal cell keratin was also found in the HI-M and HI-F tumors, while the AT-1, AT-2, MAT-Lu, MAT-LyLu, and AT-3 were negative with this antibody. Thus, a loss in staining for basal cell keratin was consistently associated with the most advanced state of tumor progression. Vimentin-positive staining was demonstrated either alone or with keratin-positive staining in part of the epithelial cancer cells of all the sublines. An increase in the positive staining for vimentin was consistently associated with a more advanced state of tumor progression. Desmin-positive staining was found only in smooth cells present within the various tumor sublines.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intermediate filament expression and the progression of prostatic cancer as studied in the Dunning R-3327 rat prostatic carcinoma system. 266 36

Two hundred and eighty-six patients presenting with metastatic adenocarcinoma or undifferentiated carcinoma whose primary site was not identified by clinical history, physical examination and chest radiograph have been studied. Median survival from presentation was 22 weeks. Factors independently predicting improved survival were lymph node presentations, good performance status and body weight loss of less than 10 per cent. In 88 (31 per cent) patients the primary tumour site was subsequently identified, in 58 (20 per cent) during life. Lung cancer was the most frequently identified primary tumour, and in only 32 (11 per cent) of the patients was a 'treatable' primary tumour (i.e. germ cell, breast, ovarian, prostate, thyroid cancer or lymphoma) identified. Among the treatable primary tumours were those in eight out of 16 female patients presenting with axillary metastases who were subsequently shown to have primary breast cancer and four of 13 females presenting with ascites who were found to have primary ovarian cancer. Prostatic cancer was confirmed in five out of 13 men with raised serum acid phosphatase. Of 22 patients with elevated serum alphafoetoprotein (AFP) or beta-human chorionic gonadotrophin levels (beta HCG) 18 had some features of the 'atypical teratoma syndrome'. Of the total of 32 patients with treatable tumour types, 29 (90 per cent) were identified during life. Median survival for patients with treatable tumour types identified during life was 104 weeks, compared with 22 weeks for the group as a whole. Retrospective immunocytochemical staining of the original biopsy showed that prostatic specific antigen and antibodies to beta HCG and AFP were diagnostically useful, but a series of organ site non-specific markers of histogenesis or cellular differentiation (carcinoembryonic antigen, secretory component for IgA, peanut lectin binding, epithelial membrane antigen and keratin) showed no significant correlations with identified primary sites, responsiveness to empirical chemotherapy or survival. Metastatic undifferentiated carcinoma or adenocarcinoma from an unknown primary site represents 6.5 per cent of all referrals to the medical oncology unit, Royal Prince Alfred Hospital, Sydney. We offer guidelines for the rapid identification of the limited number of primary sites for which effective and specific forms of systemic treatment are available.
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PMID:Metastatic adeno or undifferentiated carcinoma from an unknown primary site--natural history and guidelines for identification of treatable subsets. 365 56

Prostatic ductal (endometrioid) adenocarcinoma has been considered a distinct pathologic and clinical entity since it was first described more than 30 years ago. Its current status as a unique neoplasm is controversial, however, because it has considerable histologic overlap with typical acinar adenocarcinoma, particularly in small specimens such as needle biopsies. There are also conflicting views regarding its clinical behavior. We recently encountered a series of typical peripheral zone cancers of the prostate gland with prominent papillary or cribriform pattern that apparently did not involve the large periurethral prostatic ducts or verumontanum. To determine the incidence of these "ductal features" in nonductal carcinoma, we reviewed the findings in 338 consecutive totally embedded whole-mount prostatectomy specimens with typical clinical and pathologic features of acinar carcinoma. We defined carcinoma with significant "ductal features" as one that displayed papillary or cribriform pattern involving an arbitrarily defined aggregate focus at least 5 mm in diameter. Anti-keratin 34beta-E12 immunohistochemical staining for basal cells allowed exclusion of areas of papillary or cribriform pattern of high-grade prostatic intraepithelial neoplasia. We identified carcinoma with ductal features (papillary or cribriform growth) in 17 prostatectomy specimens (5% of cases) exclusively in the peripheral zone without involving the periurethral region. Papillary pattern was present in 11 of these cases (65%) and cribriform pattern in 10 (59%), including 4 cases (24%) with both patterns. Of 11 needle biopsy specimens available for examination from these 17 cases, 4 (36%) contained at least focal papillary or cribriform pattern of carcinoma. We conclude that adenocarcinoma arising in the peripheral zone of the prostate gland may display ductal carcinoma features (papillary or cribriform growth) classically associated with ductal adenocarcinoma. These findings, together with the recognized near-constant association of prostatic ductal adenocarcinoma and typical prostate cancer, suggest that ductal adenocarcinoma results from spread of typical prostatic acinar carcinoma into the large accommodating periurethral ducts and stroma, and that there are no unique histologic features other than site of growth. Identification of papillary or cribriform growth of cancer in prostate needle biopsies usually results from peripheral zone adenocarcinoma and not ductal adenocarcinoma.
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PMID:Does prostatic ductal adenocarcinoma exist? 1040

Pattern and cellular changes attributable to neoadjuvant hormonal therapy (NHT) might cause the unwary pathologist to overgrade or fail to recognize a treated prostatic cancer. Overdiagnosis and overgrading of surgical resections and biopsies can be avoided if an appropriate history of therapy is conveyed with the surgical specimen and if the pathologist is aware of the altered morphology of prostatic cancer treated by NHT alone or NHT plus radiation. Study of three prostatectomy specimens with post-NHT predominance of neuroendocrine cells showed positive staining for prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as staining for chromogranin and synaptophysin in Paneth-like and small neuroendocrine cells. Difficult-to-interpret needle biopsies and transurethral resection (TUR) biopsies of prostate, where the urologic pathologist's suspicion of a radiation effect was confirmed by additional history, showed absence of the basal cell layer with 34 beta E12 keratin immunostaining in prostatic cancer glands, while basal cells were present in the nonneoplastic glands with radiation-induced atypia. Postradiation salvage prostatectomy specimens showed greater apoptosis after combined NHT and radiation than after radiation without NHT. Changes attributable to radiation and radiation plus NHT are illustrated.
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PMID:Difficulties in interpreting specimens after neoadjuvant hormonal therapy and radiation with illustration of neuroendocrine differentiation. 1106 65


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