Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum activities of bone alkaline phosphatase (b-ALP) and of tartrate resistant acid phosphatase (tr-ACP) were evaluated in 271 cancer patients; 120 of them had bone metastases (BM) and 151 had none. Correlation coefficients, specificities, sensitivities, negative and positive predicting values were computed. They showed the important contribution that these isoenzymes can bring to the diagnosis of BM in 80 patients with prostate cancer, and to the followup of 191 patients with breast cancer. The assay results were analysed in parallel with bone scan and radiography. They were also compared to those of serum antigens: PSA and PAP for prostate cancer, and CEA and CA15.3 for breast cancer. These results clearly indicate that both isoenzymes are better correlated with BM than antigens, these antigens being markers of the whole tumor burden--primary tumor, metastases, recurrence--whereas b-ALP and tr-ACP are specific markers of bone metabolism.
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PMID:[Evaluation of two serum isoenzyme phosphatases as bone metastasis markers]. 208 Dec 81

In the presence of prevalent bone metastases, the precise histo-pathological diagnosis of the primary tumor is often difficult. The authors study the diagnostic value of systematic serum assay of a series of tumoral tracers (ACE, AFP, PAP and PSA, SCC, CA 19:9, CA 15:3, CA 125) which until now were used in evolutive and therapeutic monitoring. 34 patients were selected for this preliminary retrospective study (including 20 with a demonstrated histopathological diagnosis). 70 p. cent of prevalent bone metastases express a target tracer corresponding to the initial location. In some cases, an elevated tracer, because of its specificity, may bring about a diagnostic or therapeutic decision (always according to the context). No conclusion may currently be drawn in case of discordance between the anatomo-clinical context and the "profile" of the markers (1 case in our series).
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PMID:[Systematic study of various tumoral markers in prevalent bone metastasis]. 275 18

Prostate cancer with marked neuroendocrine (NE) differentiation belongs to the hormone resistant carcinomas. We report the development of TSH-secreting small cell prostate cancer (SCPC) from high grade adenocarcinoma (Gleason score 8) with an elevated number of chromogranin A positive cells located in benign structures adjacent to the cancer. Conversion to SCPC was followed-up during 4 years. The initial adenocarcinoma exerted a stronger positivity for PAP than for PSA (respective staining indexes, Sls, 2.2 and 1.8, maximum staining 3.0). In the developed SCPC, 2 cell subpopulations that were derived from epithelial cells were found (positive stain for EMA and CEA, respectively) and from one of them originated CEA-positive liver metastases. Blood CEA and NSE levels were elevated in SCPC (284 ng/ml and 24.5 ng/ml). However, blood TPS level which reflects proliferation of epithelial cells was within the normal range. The development of a << pure >> sarcomatoid prostatic tumor from adenocarcinoma with 2 areas of similar differentiation grades (Gleason score 7 and 9-10) that initially differ in staining for PSA and PAP (SIs for PSA were 1.2 and 0.02 and for PAP were 1.6 and 0.02, respectively) was followed-up during 4 years of treatment with Estracyt. Adenocarcinoma tissue specimens was slightly CEA-positive. The disappearance of lower grade adenocarcinoma during treatment was accompanied by the development of sarcomatoid areas that were 100% vimentin positive. In the last year of follow-up the primary tumor was composed only of vimentin positive sarcomatoid cells with a slight positivity for Chromogranin A, NSE and ACTH. In parallel, normal serum PSA and PAP values and elevated CEA and NSE serotests (12.6 ng/ml and 24.7 ng/ml, respectively) were found. Blood TPS level was at the upper limit of the normal range. Scintigraphy revealed extensive liver metastases. The recorded data indicate (i) extremely poor prognoses associated with high grade adenocarcinomas that demonstrate stronger immunohistochemical positivity for PAP than that for PSA (ii), chromogranin A positive cells in benign structures adjacent to the cancer as a possible paracrine promoter of SCPC from poorly differentiated adenocarcinoma, and (iii) a high degree of heterogeneity of both SCPC and sarcomatoid prostatic neoplasms with some evidence for definite links (EMA and CEA) to secretory epithelial cells.
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PMID:Immunohistochemical staining and serotest markers during development of a sarcomatoid and small cell prostate tumor. 784 May 15

The dynamic evaluation of tumor markers is a promising area of investigation which is expected to provide clinical information when serial samples are available from the same patient. This is feasible in the post-operatory evaluation, during the follow-up after the treatment for to the primary tumor and in the monitoring of the treatment for metastatic disease. Variations among serial samples may be assessed using both empirical and mathematical approaches. Empirical approaches rely on overcoming a given percentage usually chosen on the base of arbitrary decisions. Mathematical approaches include the actual half-life, the doubling time, a dose/time regression analysis and the calculation of the critical difference. The two former are currently used in clinical practice whereas the two latter are still matter of investigation. As concerns the assessment of the radicality of the surgery for the primary tumor, the serum markers are used in germ cell tumors and in prostate cancer. The half-life of the markers is the decision criteria used in germ cell cancers, while in prostate cancer PSA is expected to be undetectable more than 30 days after the radical prostatectomy. Tumor markers are currently used during the follow-up of several malignancies after the treatment for primary tumor. Although several samples are available, decision criteria are still based on positive/negative cut-off values in several instances. Promising dynamic approaches are under investigation and are expected to lead to earlier and probably more accurate information concerning the disease progression. A critical point still under debate is the actual impact of tumor markers on patients' survival in malignancies incurable when metastatic, such as colorectal cancer and breast cancer. This matter urgently demands perspective clinical studies. Finally, the dynamic use of tumor markers is now commonly applied in the monitoring of the therapy for metastatic malignancies. In this clinical setting mathematical criteria are used for ovarian and and germ cell tumors with promising results. Nevertheless, the use of empirical criteria, namely the percentage of variation between two consecutive samples, is successfully used for the monitoring of the therapy of metastatic breast cancer. In conclusion, when several samples are available from an individual patient they may be evaluated according to dynamic criteria instead of referring to a conventional positive/negative cut-off point. Although mathematical decision criteria are expected to provide more reliable data, empirical approaches are used as well and provide useful information in decision making.
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PMID:Dynamic use of tumor markers, rationale-clinical applications and pitfalls. 869 56

RT-PCR, if targeted against a prostate-specific marker, can be a highly specific and sensitive assay to detect the presence of occult prostate cancer cells at sites far distant from the primary tumor. The low false-positive rate (0.8%) observed when combining most published studies and the high rate of detection of prostate cells in metastatic patients (88%) found in well-defined clinical studies address the basic requirements of a clinically effective diagnostic modality. Additionally, all reports indicate that RT-PCR positivity for PSA or PSMA increases with increased stage of prostate cancer, suggesting that RT-PCR assays may have value in staging the patient presumed to have clinically localized disease. Indeed, data from two institutions have shown the unique contribution that RT-PCR technology might lend to this most vexing problem. With the suggestive data already published, we remain optimistic that molecular staging will become a reality in the future. After all, the variability in techniques of RT-PCR (as well as differences in targets and samples assayed) used by the various laboratories now investigating this method could themselves be responsible for many of the differences reported. There is no question that standardization among laboratories is essential before clinical utility of molecular staging can be proved. Indeed, this endeavor represents the major aim of the RT-PCR consortium in the United States. Nevertheless, at our own medical center, we are struck by our finding that if a preoperative RT-PCR for PSA is negative, the patient can be assured of a successful operative outcome in 88% of cases. We also are impressed by the data showing that if the serum PSA level is greater than 10 ng/mL and the RT-PCR assay is positive, 90% of patients undergoing radical surgery have adverse pathology reports (and, in fact, have already experience operative failure in nearly half the cases). There is increasing consensus that RT-PCR assays afford prognostic information that is also unique. Three institutions have similar data comparing operative or preoperative RT-PCR strategies (employing all three potential sample sources) with treatment outcome. This may suggest the validity of RT-PCR as a staging modality or, alternatively, suggest that a truly metastatic phenotype is identified in patients with circulating PSA-synthesizing cells, or in patients harboring PSA-synthesizing cells in node or marrow tissues. In either case, RT-PCR appears already to provide information not available before the use of this technology. In fact, in the only series comparing RT-PCR with other, more established predictors (PSA, Gleason score) in a multivariate analysis, RT-PCR status provided the best prognostic information. Prostate manipulation does, in fact, appear to affect the RT-PCR assay. Although digital rectal examination and cystoscopy do not seem sufficiently invasive to release prostate cells into the circulation, a small number of individuals undergoing transrectal ultrasound biopsy will experience this phenomenon. This observation provides a cautionary note relative to timing of sample collection for RT-PCR assays. Furthermore, a significant fraction of patients undergoing prostate manipulation during radical surgery may experience shedding of prostate cells into the operative field and release of some into the peripheral circulation. This has not been universally observed and, even if true, may not share the significance of spontaneous RT-PCR positivity (before prostatic manipulation). In the one instance, a potentially metastatic phenotype is responsible for RT-PCR positivity, whereas in the other instance, PSA or PSMA synthesizing cells may have no metastatic potential at all. Further studies on the biologic half-life of such cells are required before any clinical judgement can be made regarding this phenomenon. In summary, there appears to be consensus that RT-PCR technology can differentiate controls from patients with metas
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PMID:Reverse transcriptase-polymerase chain reaction assays for prostate cancer. 912 34

Capromab Pendetide imaging illustrates the successful translation of monoclonal antibody technology from the laboratory to the clinic. It provides a means of identifying otherwise occult soft tissue metastases in patients with adenocarcinoma of the prostate. When utilized with other clinical, pathological and laboratory findings, Capromab Pendetide imaging enables more accurate disease staging and monitoring than is afforded by other imaging modalities such as CT and MRI. In the primary disease setting Capromab Pendetide imaging should be reserved for use in patients with negative bone scans who are at high risk for metastatic disease based on such factors as advanced clinical stage, high Gleason score and significantly elevated serum PSA or alkaline phosphatase. Due to low sensitivity for small-volume disease, a negative Mab scan may not eliminate the need for a staging lymph node dissection but should encourage further consideration of local treatment options. Capromab Pendetide should be used with caution in patients at low risk for metastatic disease. Positive scan findings in low risk patients should be confirmed before altering the treatment plan since some false positive scans should be anticipated in a population with low disease prevalence. Capromab Pendetide imaging has not been shown to be reliable in determining the local extent of the primary tumor but new techniques involving co-registration of SPECT and CT images show promise in this regard. In the patient with recurrent disease following primary therapy, the predictive value of Capromab Pendetide imaging of the prostate or prostate fossa is limited, particularly following RT. Its more important role in this setting is to identify lymph node metastases in the high risk patient with a negative bone scan who might otherwise be a candidate for local salvage therapy. A large prospective study is needed for confirmation, but preliminary data suggest that Capromab Pendetide imaging is helpful in identifying those patients with PSA elevation after radical prostatectomy who are most likely to benefit from salvage RT. As with any imaging technique, Capromab Pendetide has strengths and weaknesses that must be understood to maximize patient benefit by utilizing the scan in clinical settings where it is most likely to be useful and least likely to be misleading. Capromab Pendetide is a technically demanding procedure best performed and interpreted at sites with experience and expertise.
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PMID:Capromab Pendetide imaging of prostate cancer. 1080 17

PSA is an oncodevelopmental antigen usually expressed in human tumors with high metastatic potential. Here we set up a metastatic model in nude mice by using TE671 cells, which strongly express PSA-NCAM. We observed the formation of lung metastases when TE671 cells were injected intravenously, intramuscularly, and intraperitoneally, but not subcutaneously. Intraperitoneal injections also induced peritoneal carcinosis, ascites, and liver metastases. To evaluate the putative role of PSA in the metastatic process we used a specific cleavage of PSA on NCAM by endoneuraminidase-N on intraperitoneal primary tumors. Mice with primary intramuscular tumors were taken as control. Repeated injections of endoneuraminidase-N led to a decrease in PSA expression in primary intraperitoneal nodules and ascites but not in intramuscular primary tumors. Endoneuraminidase-N also increased the delay in ascitic formation and decreased the number of lung or liver metastases in the case of intraperitoneal tumors but not in the case of intramuscular tumors. When metastases occurred in endoneuraminidase-N injected animals, they strongly expressed PSA-NCAM. Therefore, we established a relationship between PSA expression on the surface of primary tumor cells and the metastatic process.
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PMID:A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the role of polysialic acids in the metastatic process. 1131 35

Prostate adenocarcinoma (PA) is known to metastasize widely to bone, lung, lymph nodes, and other sites. We have observed a rare, although distinctive, neuroendocrine (NE) cytomorphology of metastatic PA on fine-needle aspiration (FNA) that mimics small cell carcinoma (SCC). From a total of 117 cases, eight cases of metastatic PA diagnosed on FNA showed cytomorphologic features indistinguishable from SCC. All specimens were reviewed, along with immunoperoxidase (IPOX) studies using prostate specific (PSA, PSAP) and NE markers (synaptophysin, chromogranin, etc.). The patients ranged in age from 51-68 (mean age = 63). The PSA levels at the time of FNA ranged from <0.1 to 2,892 ng/ml (normal postprostatectomy <0.2 ng/ml). Sites of FNA included liver (two), soft tissue (five), and lymph node (one). FNA was performed from 11 mo to 6 yr after the initial diagnosis of the primary tumor. All primary PA were of high Gleason grade ranging from 7-9. None of the primary PA showed neuroendocrine morphology. Cytomorphologic characteristics observed on FNA included predominantly single cells with occasional sheets or loose cell aggregates. A predominant NE nuclear morphology was evident (i.e., hyperchromasia, fine dusty chromatin, inconspicuous nucleoli, nuclear molding, chromatinic crush artifact, karyorrhexis, mitoses, etc.), with none of the tumors displaying glandular formation. Taken together, these features gave these metastases a cytomorphology indistinguishable from SCC. IPOX studies revealed PSA-positivity (5/7), PSAP-positivity (4/7), and only focal NE markers positivity (3/6). Metastatic prostate carcinoma may rarely mimic a SCC (6.8% in this study). This often necessitates further patient workup to identify the primary source for the patient's metastasis, particularly if the patient has multiple lesions. An accurate diagnosis of these lesions as PA metastases is essential for effective, timely treatment and therapeutic design.
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PMID:Prostatic adenocarcinoma metastases mimicking small cell carcinoma on fine-needle aspiration. 1220 72

A 63-year-old man was admitted to our hospital for complaints of a painless knot in his right testicle. The patient underwent orchiectomy for suspicion of malignancy. Pathologic examination detected a firm, circumscribed mass that consisted histologically of noncohesive, large, undifferentiated tumor cells diffusely infiltrating the testicular interstice. Because of the patient's advanced age and the structure of the neoplastic cells, the differential diagnosis favored a lymphoma over a malignant germ cell tumor but also included a dedifferentiated metastatic neoplasm. Immunohistochemistry was tailored accordingly and was completed using three successive panels of antibodies. Immunostaining with the first panel of antibodies directed against leukocyte epitopes (CD45, CD20, and CD3) remained negative and made a lymphoma unlikely. The subsequent panel (cytokeratin AE1/3, cytokeratin 18, and HMB-45) helped to rule out a malignant melanoma and aided to settle the diagnosis of a metastatic carcinoma. The reaction pattern of the last panel of antibodies pointed to a pulmonary origin of the putative primary tumor (PSA-negative, TTF-1-positive, and CK20-negative). The diagnosis of a metastasized poorly differentiated adenocarcinoma of the lung was confirmed by autopsy 5 months later. This case represents the extremely rare occurrence of a testicular metastasis as a primary manifestation of an occult neoplasm and shows the usefulness of an integrated site-specific clinicomorphologic approach that should precede and guide the choice of diagnostic immunoreagents.
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PMID:Immunohistochemical assessment of a testicular tumor in a 63-year-old patient: proposal for an integrated clinicopathologic approach. 1261 Mar 64

Although multiple studies have addressed the prognostic importance of tumor differentiation in patients with clinically localized prostate cancer, few data are available in patients with metastatic disease. We evaluated and compared survival data in two groups of men with Whitmore stage D2 metastatic prostate cancer initially treated with hormonal therapy. A series of 76 patients with D2 metastatic disease were evaluated and treated at the National Cancer Institute (NCI) in conjunction with an additional cohort of 141 patients from the Louisiana State University School of Medicine (LSU). Pathological specimens were classified according to the Gleason score. Fifty-two (25%) of the combined NCI/LSU specimens had a Gleason score of 6 or less, 71 (34%) had a value of 7, and remaining 87 (41%) had scores between 8 and 10. The median PSA at the time of diagnosis for the NCI patients was 294.2 ng/ml. Time to treatment failure was defined as the time that a greater than 50% increase above nadir PSA was noted. In neither group was Gleason score correlated with overall survival. There was no association between the time to progression following hormone therapy and primary tumor Gleason score. The PSA concentration at the time of diagnosis was not correlated with the Gleason score for the NCI patients; however, there was an inverse correlation between pretreatment PSA level and time to progression following hormonal ablation. Gleason score does not appear to impact survival in metastatic prostate cancer. PSA as a marker of the biological behavior in metastatic disease may also be limited. These findings should be reevaluated in larger, better matched cohorts. Novel techniques such as serum proteomics, microarrays, and metastatic cell isolation methods may better predict outcome in advanced prostate cancer.
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PMID:Gleason score and pretreatment prostate-specific antigen in survival among patients with stage D2 prostate cancer. 1559 75


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