[Usefulness of PSA-complex in the diagnosis of prostatic carcinoma]. / Utilidad del PSA-complex en el diagnóstico del carcinoma de próstata.

OBJECTIVE: Since its discovery as a marker for prostate cancer, there have been many attempts to enhance the diagnostic efficacy of the prostate specific antigen (PSA). Among these are the studies that analyze the behavior of different forms of serum PSA bound to different antiproteases, such as alpha-1-antichymotrypsin, which forms the complexed PSA (PSA-c). This study analyzed the utility of PSA-c to enhance specificity without altering sensitivity in comparison to total PSA (PSA-t). METHODS: From September 1998 to March 1999, blood samples were obtained from 96 patients that had undergone a prostate biopsy due to a suspicion of prostate cancer. PSA-c, PSA-t (Technicon Immunol system, Bayer) and PSA-c/PSA-t ratio were analyzed in these patients. RESULTS: ROC curves were plotted and the optimal cutoffs were found for which the specificity was higher for PSA-c (44.6% [CI 95%, 32-57]) versus PSA-t (35.4% [CI 95%, 25-49]) and the PSA-c/PSA-t ratio (38.5% [CI 95%, 27-51]) while maintaining a similar sensitivity index (90%). PSA-c showed similar results for other values of sensitivity. CONCLUSIONS: PSA-c was found to improve specificity in comparison to PSA-t and PSA-c/PSA-t ratio. PSA-c determination could avoid unnecessary biopsies without altering sensitivity; i.e., the same number of prostate cancers will be detected.

[New quantitative method for determining p53 protein in bladder carcinomas]. / Nuevo método cuantitativo para determinar la proteina P53 en carcinomas vesicales.

OBJECTIVE: To continue a study protocol on the molecular biology of bladder tumors, analyze protein p53 expression using a new quantitative analytical method and the biological implications of the changes in p53 expression. METHOD: From January, 1993 to January, 1995, 74 patients were studied. These patients were divided into two groups: the first group comprised 14 controls of urothelial tissue and the second comprised 60 cases of transitional cell carcinoma of the bladder. A quantitative method of immunoluminescence (LIA-mat p53 method) was utilized to analyze p53 expression. RESULTS: Tissue oncoprotein p53 was higher in patients with bladder carcinoma than in healthy urothelial tissue. Higher values of protein p53 was found in infiltrating and undifferentiated tumors and in those patients who died than in those who are alive. CONCLUSION: Protein p53 determination using this new quantitative method permits identification of subgroups of patients with tumors that have a more aggressive biological behaviour.

[Advances regarding tumor markers in bladder cancer]. / Avances en marcadores tumorales en cáncer vesical.

INTRODUCTION: Currently, there is not known tumoral marker for vesical carcinoma that would allow to distinguish when a surface tumour may become invasive. OBJECTIVE: To analyze the functionality of a series of biological substances (CEA, CA 50, CA 19.9 and TPS) in vesical carcinoma. MATERIAL AND METHODS: Between September 1992 and June 1994, a total of 385 biological specimens divided into two groups were analyzed. The first group comprised 271 serum samples from 81 control subjects and 190 patients with vesical carcinoma. The second group included 114 urothelial tissue samples (56 controls and 58 vesical carcinoma). Serum and tissue levels of CA, CA 50, CA 19.1 and TPS were determined in both groups by fluoroimmunoassay, RIA and IRMA, respectively. An statistical evaluation was done using Student's 't' and/or Mann-Whitney tests depending on whether data distribution adjusted to normal or not. RESULTS: Patients with vesical carcinoma, ana within this group those with infiltrant tumours, showed higher CEA serum levels. Also CEA tissue levels found in neoplastic vesical urothelium were higher than those in the control group (p < 0.05). Tissue levels were higher in infiltrant tumours. Higher TPS serum and tissue levels were found in the vesical tumours group. Same as with CEA, CA 50 also exhibited higher serum levels in the group with vesical Ca than in the controls (p < 0.01). Likewise, CA 50 tissue values were higher in the group with vesical Ca, more specifically in the infiltrant tumours group (p < 0.001). Statistically significant differences become apparent when the above values were compared to tissue samples from the control group (p < 0.001). On the other hand, serum CA 19.9 levels were lower in the vesical carcinoma group although tissue levels were higher in the vesical Ca group (p < 0.001). CONCLUSIONS: Transitional cell vesical carcinoma is a tumour that produces and secretes CEA, CA 50, CA 19.1 and TPS. CEA and CA 50 levels could be used as prognostic factors.

[The molecular biology of bladder carcinoma]. / Biología molecular del carcinoma vesical.

OBJECTIVE: The clinical course of transitional cell carcinoma of the bladder can be difficult to predict due to its potential to invade the muscle layer and/or develop to a high grade lesion. Bladder carcinoma can arise from genetic changes that may activate the oncogenes (-c-erbB2, c-erbB1, c-myc, ras, etc.) and/or inactivate the suppressor genes (p53, Rb). The aim of the present study is to continue a study protocol on the molecular biology of bladder tumors. METHODS/RESULTS: From January, 1993 to January, 1995, 85 patients were studied. These patients were divided into two groups: the first group comprised 14 controls of urothelial tissue and the second comprised 65 cases of transitional cell carcinoma of the bladder. p53 expression was determined by an immunohistochemical method (NCL-p53-DO7 monoclonal antibody). Quantification of the p8 oncoprotein in cytosol and EGFR (epidermal growth factor receptor) in membrane was performed by ELISA (Oncogene Science) and RIA (Vienna Lab), respectively. A statistically significant relationship between the expression of p53 and EGFR with tumor stage and grade was found. Quantification of p185 and EGFR showed higher values in the tumor tissue than in the control samples, but a worse survival could not be determined. CONCLUSIONS: The present study shows that p53 expression can be considered to be a prognostic factor. It provides useful information on the aggressive behaviour of the tumor and has a direct relation with the survival rates.

[Serum and tissue quantification of tissue polypeptide antigen (TPA) in transitional cell carcinoma of the bladder]. / Cuantificación sérica y tisular de antígeno polipeptídico tisular (TPS) en el carcinoma transicional de vejiga.

Tissue polypeptide antigen (TPA) is a marker of proliferative cellular activity. The aim of this paper is to demonstrate the production of this marker in bladder carcinomas and to study the biological behaviour in this type of patients. From September, 1992 to June, 1993, we studied 50 patients divided into two groups. The first group comprised healthy subjects and the second one comprised 30 patients with bladder carcinoma. In both groups, we determined the TPS in blood and tumoral tissue by RIA (TPS-IRMA Beki-Diagnostic AB). Our results demonstrated higher levels of TPS in tumoral tissue and blood than in healthy subjects (1887.83 and 197.33 vs 231.5 and 58.23 IU/ml) and higher levels of tissular and blood TPS for the undifferentiated tumors (989.66 and 231.5, 1748.2 and 210, 1842.6 and 219, 2010.7 and 220 IU/ml for Broders' classification 1, 2, 3 and 4).

[Involvement of epidermal growth factor receptor (EGFR) in the etiopathogenesis of prostatic proliferative processes]. / Implicación del receptor del factor de crecimiento epidérmico (EGFR) en la etiopatogenia de los procesos proliferativos prostáticos.

The prostatic growth factors require a membrane specific receptor to which they must bind in order to carry out their biological activities correctly. The aim of this study was to isolate and quantify the epidermal growth factor receptor in prostatic tissue and indirectly determine the growth factors acting on it (EGF, TGF alpha, PDGF, NGF, IGF). From September, 1992 to June, 1993, we studied 55 patients. These were divided into two groups: the first group comprised 49 patients with benign prostatic hyperplasia (BPH) and 6 patients with prostatic carcinoma comprised the second group. Samples of the prostate were obtained following suprapubic (12 cases), TUR (38 cases), radical prostatectomy (1 case) and transrectal biopsy (4 cases). The EGFR was determined by radioimmunoassay (EGFR-RIA, Vienna Lab, Labordiagnostica GmbH). For the overall group of patients, we obtained mean EGFR values of 6.36 +/- 0.59 fmol/mg of protein and a positivity of 96.36% and 100% for BPH and malignant proliferative processes, respectively. The foregoing data show that EGFR was isolated from the tissue we analyzed and has an evident role in the regulation of prostate growth.

[Quantitative determination of epidermal growth factor urothelial receptor (EGFR) in superficial and invasive bladder carcinoma]. / Dosificación cuantitativa del receptor urotelial del factor de crecimiento epidérmico (EGFR) en carcinomas vesicales superficiales e invasivos.

The epidermic growth factor (EGF) is a polypeptide which stimulates tissue proliferation. The mechanism of action takes place through an specific membrane receptor, known as the EGFR. Recent scientific contributions have allowed to know its implication in various tumoral processes (breast, ovary, bladder, etc), so that its expression may be used as a major prognostic factor. The objective of this work is to quantify and analyze the epidermic growth factor receptor (EGFR) in surface and invasive vesical carcinoma. To this end, 43 tissular samples divided in two groups were studied. The groups were: 1) Group 1 or control group, comprising 14 samples of "control" vesico-urothelial tissue, and 2) Group 2, assembling 29 patients with vesical carcinoma (17 surface and 12 infiltrant). All tissue samples underwent a process of homogenization and subsequent determination of membrane EGFR by means of radioimmunoassay (EGFR-Receptor Assay, Vienna Lab, Labordiagnostika GmbH). Our results demonstrate the expression of EGFR in both control and tumoral vesico-urothelial tissue in 100% of cases, with detection of significantly higher concentrations (p) in samples from vesical carcinoma than in those from control specimens (15.24 vs. 5.02 fmol/mg protein) and higher levels in infiltrant rather than in surface vesical carcinomas (18.92 vs. 11.4 fmol/mg protein).

[Determination of serum SCC antigen in transitional cell carcinoma of the bladder]. / Dosificación sérica de antígeno SCC en el carcinoma vesical de células transicionales.

The SCC antigen expresses in the squamous epithelium during the process of a neoplastic transformation. This paper's objective is to evaluate the biological behaviour of SCC antigen in surface, deep, localized and spread malignant vesical carcinoma. To this end, 100 patients divided in two groups were studied. The first group consisted in 30 healthy subjects strictly selected and the second group comprised 70 patients diagnosed with transitional cell vesical carcinoma. SCC Antigen measurement was made by Radioimmunoassay (RIA, Abbott). Our results suggest that this tumoral antigen has no use as a prognostic factor in patients diagnosed with transitional cells vesical carcinoma, since serum concentrations suffer no change in relation to size, extent and degree of tumoral differentiation.

[The usefulness of the carbohydrate antigen CA-50 in the prognosis of transitional-cell bladder carcinomas]. / Utilidad del antígeno carbohidratado CA 50 en el pronóstico en los carcinomas vesicales de células transicionales.

The carbohydrate antigen CA 50 is expressed in the epithelial tissue during the process of neoplastic transformation; i.e., transitional cell bladder carcinoma. The present study evaluated the biological behaviour of the CA 50 antigen in malignant superficial, deep localized and disseminated bladder tumors. One hundred subjects were entered into the study: 30 carefully selected healthy subjects comprised the first group and 70 patients with a diagnosed transitional cell bladder carcinoma comprised the second group. The serum CA 50 antigen was determined by immunofluorometric assay (Delfia CA 50 kit). Our results indicate that the carbohydrate CA 50 antigen can be utilized as a prognostic marker in patients with malignant bladder tumors. The serum antigen levels were higher for the more undifferentiated tumors and those in the advanced stages.

[Basic concepts in the use of tumor markers in the diagnosis and follow-up of malignant bladder neoplasms]. / Conceptos básicos en la utilización de los marcadores tumorales en el diagnóstico y seguimiento de las neoplasias vesicales malignas.

The absence of reliable diagnostic elements for the evaluation of malignant bladder tumors and the low sensitivity of the conventional diagnostic methods have prompted studies on the biological behaviour of this tumor type. The well known studies of Gold and Freedman and the recent investigations of Bates and Logo have proposed using tumor markers for early diagnosis and follow-up of different types of malignant tumors. However, the "ideal" tumor marker, one that is sufficiently sensitive and specific, has as yet to be discovered. We reviewed the tumor markers widely utilized to diagnose and follow-up malignant bladder tumors, and describe their main features. It must be pointed out that the lack of sensitivity and specificity of these tumor markers have led to the development of a new generation of tumor markers, such as cytogenetic markers, oncogenes, etc. Undoubtedly, this review of the literature will become obsolete with the advent of subsequent generations of tumor markers.