Prostatic Neoplasms: Molina R

Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Holten-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih IeM, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP, Anonymous00039. · Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK. · Clin Chem. · Pubmed #19042984 No free full text.

Abstract: BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast, and ovarian--were critically reviewed. RESULTS: For testicular cancer, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. alpha-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is <10 microg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node-negative patients. CA15-3/BR27-29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer. CONCLUSIONS: Implementation of these recommendations should encourage optimal use of tumor markers.

Filella X, Truan D, Alcover J, Quintó L, Molina R, Luque P, Coca F, Ballesta AM. · Department ofClinical Biochemistry, IDIBAPS, Hospital Clínic, Barcelona, Catalonia, Spain. · Urology. · Pubmed #15183958 No free full text.

Abstract: OBJECTIVES: To compare the diagnostic efficacy of prostate-specific antigen (PSA) and the PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between prostate cancer and benign prostatic hyperplasia. METHODS: We measured the serum levels of total PSA (tPSA; Hybritech and Bayer), fPSA (Hybritech), and cPSA (Bayer) in 72 patients with prostate cancer and 128 patients with benign prostatic hyperplasia. RESULTS: Receiver operating characteristic curves were used for comparison of these tests. The greatest area under the curve was observed for the fPSA/cPSA ratio and the fPSA/tPSA ratio (0.757 and 0.754, respectively). The substitution of the fPSA/tPSA ratio with the fPSA/cPSA ratio in the diagnostic scheme of prostate cancer improved the diagnostic accuracy, with similar sensitivity and an increment in specificity (41% versus 45%). CONCLUSIONS: The fPSA/cPSA ratio ensures a reduction in negative biopsies in the PSA gray zone. We suggest substituting the fPSA/tPSA ratio with the fPSA/cPSA ratio for patients with a PSA level between 4 and 10 ng/mL.

Domingo-Domenech J, Fernandez PL, Filella X, Martinez-Fernandez A, Molina R, Fernandez E, Alcaraz A, Codony J, Gascon P, Mellado B. · Department of Medical Oncology and Laboratory of Experimental Oncology, Institut Clínic de Malalties Hemato-Oncològiques, Barcelona, Spain. · Ann Oncol. · Pubmed #17998285 links to  free full text

Abstract: BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression has been linked to hormone-independent prostate cancer (HIPC) progression. Its clinical value and correlation with therapy is not defined. PATIENTS AND METHODS: Patients with HIPC treated with docetaxel (Taxotere) were prospectively tested for serum HER2 extracellular domain (ECD) by immunoanalysis. HER2 was determined by immunohistochemistry and fluorescence in situ hybridization (FISH) in tumor samples. RESULTS: Sixty-nine patients were included. Twenty-four (34.8%) patients had high HER2 ECD (>15 ng/ml). Prostate-specific antigen (PSA) response was 58% for patients with low HER2 ECD and 36% for patients with high HER2 ECD (P = 0.046). HER2 ECD levels were an independent prognostic factor for time to PSA progression [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.22-6.50; P = 0.015] and overall survival (HR 3.24; 95% CI 1.38-7.59; P = 0.007). Tissue samples from 17 patients were tested for HER2. Patients with negative HER2 tissue expression had lower HER2 ECD levels (median 10.5 +/- 2.7 versus 30.5 +/- 24.8 ng/ml; P = 0.016). FISH was negative in all samples. CONCLUSIONS: High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.

Filella X, Alcover J, Molina R, Luque P, Corral JM, Augé JM, Coca F. · Department of Biochemistry and Molecular Genetics, Hospital Clinic, Barcelona, Catalonia, Spain. · Anticancer Res. · Pubmed #17348449 No free full text.

Abstract: BACKGROUND: Free prostate-specific antigen (fPSA), the minor form of total PSA, contains different molecular subforms, including BPSA and proPSA. Whereas BPSA is associated with benign prostate hyperplasia, proPSA is associated with prostate tumor. PATIENTS AND METHODS: The serum levels of PSA, fPSA and proPSA were measured using automated electrochemiluminescent immunoassays (Elecsys 2010, Roche Diagnostics) in 87 patients with prostate cancer and 138 patients with benign prostate hyperplasia. Also, we calculated the derived tests of these assays through the subtraction or the ratio between the measured tests. Results: Receiver operating characteristics curves were used for comparison of the diagnostic utility of tests assessed. The biggest areas were obtained for the free/total PSA ratio (0.705), the calculated Bfree PSA/total PSA ratio (0.719) and the calculated Bfree PSA/bound PSA ratio (0. 726). CONCLUSION: Applying a multivariate logistic regression analysis, it was determined that the combination of the proPSA concentration, the proPSA/total PSA ratio and the calculated Bfreeltotal PSA ratio improves the area under the curve obtained for individual tests (0.753). ProPSA may be useful in the diagnosis of prostate cancer.

Filella X, Truan D, Alcover J, Gutierrez R, Molina R, Coca F, Ballesta AM. · Department of Clinical Biochemistry (CDB), Hospital Clinic, Barcelona, Catalonia, Spain. · Anticancer Res. · Pubmed #15736470 No free full text.

Abstract: BACKGROUND: The description of a new method for the measurement of complexed prostate-specific antigen (cPSA) offers a new approach to the diagnosis of prostate cancer. PATIENTS AND METHODS: We measured PSA (Hybritech and Bayer), free PSA (Hybritech) and complexed PSA (Bayer) in 72 patients with prostate cancer and 128 with benign prostate hyperplasia. RESULTS and CONCLUSION: We found an increase of sensitivity using 25 and 7 ng/mL as cut-offs for cPSA in relation to total PSA using as cut-offs 4 and 10 ng/mL (96 and 36% vs. 92 and 35.5%). Similar differences were found for specificity (78% and 31% for cPSA vs. 73% and 29% for total PSA). Therefore, we defined a gray zone for patients with cPSA between 2.5 and 7 ng/mL for which the measurement of the free/complexed PSA ratio saves an important number of negative biopsies maintaining a higher sensitivity.

Filella X, Truan D, Alcover J, Molina R, Luque P, Coca F, Ballesta AM. · Servicio de Bioquímica Clínica (CDB), Hospital Clínic, IDIBAPS, Barcelona, Spain. · Med Clin (Barc). · Pubmed #15012870 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: The description of different forms of PSA has opened a new strategy in the diagnosis of prostate cancer. The measurement of the ratio between free PSA and PSA in the group of patients with a PSA level between 4 and 10 ng/ml decreases the number of negative biopsies. The aim of our study was to compare the diagnostic efficacy of PSA and PSA fractions (free PSA [fPSA] and complexed PSA [cPSA]) in the differential diagnosis between Pca and benign prostate hyperplasia (BPH). PATIENTS AND METHOD: We measured the serum levels of PSA, free PSA and cPSA in 56 patients with Pca and 94 patients with BPH. RESULTS: ROC curves were used for the comparison of tests. The biggest area under the curve (AUC) was observed for the ratios fPSA/cPSA and fPSA/PSA (0.718 and 0.712, respectively). When we compared the AUC between PSA and cPSA, then AUC for cPSA was higher than AUC for PSA (0.602 and 0.567, respectively). We observed similar results in the group of patients with PSA levels between 4 and 10 ng/ml. CONCLUSIONS: The diagnostic accuracy of cPSA is higher than that of PSA. Moreover, in the differential diagnosis between prostate cancer and BPH, the use of PSA ratios (fPSA/cPSA or fPSA/PSA) increases the diagnostic accuracy obtained with the measurement of PSA or cPSA.

Filella X, Alcover J, Corral JM, Molina R, Beardo P, Ballesta AM. · Department of Clinical Biochemistry, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, Barcelona, Spain. · Anticancer Res. · Pubmed #11848550 No free full text.

Abstract: BACKGROUND: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.

Filella X, Alcover J, Zarco MA, Beardo P, Molina R, Ballesta AM. · Unit for Cancer Research, Department of Clinical Biochemistry, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain. · Prostate. · Pubmed #10951490 No free full text.

Abstract: BACKGROUND: It has been proposed that a dysregulation in the balance between type T1 (IL-2, IFN-gamma) and type T2 (IL-4, IL-10) cytokines may be implicated in the development of cancer. METHODS: We determined the expression of IL-2, IL-4, IL-10, and IFN-gamma in CD4 and CD8 lymphocytes by flow cytometry in 12 patients with prostate cancer and in 7 healthy subjects. In addition to the basal expression of these cytokines, their expression was also determined, following stimulation of lymphocytes with PMA (phorbol 12-mystirate 13 acetate) and ionomycin. RESULTS: The basal expression of cytokines was scarce, while following stimulation this increased markedly. On the other hand, there was a dysregulation in the balance between T1 and T2 lymphocytes in patients with prostate cancer. To this effect, in relation to healthy subjects, we observed an increase in IL-10 expression and a decrease in IL-2 expression. CONCLUSIONS: The disequilibrium observed in the balance between type T1 and type T2 cytokines may be implicated in the evolution of neoplastic disease.

Filella X, Alcover J, Molina R, Corral JM, Carretero P, Ballesta AM. · Unit for Cancer Research, Department of Clinical Biochemistry, Institut d'Investigacions Biomediques August Pi i Sunyer, Hospital Clinic, Barcelona, Spain. · Prostate. · Pubmed #10639188 No free full text.

Abstract: BACKGROUND: To enhance the specificity of PSA in diagnosis of cancer, several approaches have been evaluated, having in common the study of fractions of PSA. The aim of this study was to evaluate the usefulness of complexed PSA in the differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer. METHODS: We determined the concentrations of complexed PSA (Bayer, Tarrytown, NY) and total PSA (Tandem-R Assay, Hybritech Incorporated, San Diego, CA) in 196 patients with BPH and in 55 patients with prostate cancer. Likewise, the percentage of free PSA (Wallac, Turku, Finland) was determined for 124 of these patients. RESULTS: The specificity of complexed PSA was found to be greater than that of total PSA for the cutoff values corresponding to sensitivities of 80%, 85%, and 90%. Similarly, the area under the curve obtained by receiver-operating curve analysis was greater for complexed PSA than for total PSA, although significant differences were not observed. The diagnostic usefulness of complexed PSA in the differential diagnosis between BPH and prostate cancer was found to be lower than the percentage of free PSA. CONCLUSIONS: We believe that differential diagnosis with complexed PSA between BPH and prostate cancer is of little use, due to low efficacy when PSA results are extreme.

Filella X, Alcover J, Quintó L, Molina R, Bosch-Capblanch X, Carretero P, Ballesta AM. · Department of Clinical Biochemistry (Unit for Cancer Research), 'Institut d'Investigacions Biomèdiques August Pi i Sunyer', Hospital Clínic, Barcelona, Spain. · Tumour Biol. · Pubmed #10567877 No free full text.

Abstract: The use of prostate-specific antigen (PSA) in the diagnosis of prostate cancer is controversial due to false-positive results caused by benign prostatic hyperplasia. Several groups have suggested the usefulness of the percentage of free PSA (%fPSA) in patients with PSA levels between 4 and 10 microg/l. Based on previously obtained results, biopsy is carried out in our hospital if the PSA is greater than 10 microg/l or if the %fPSA is lower than 20% and PSA is between 4-10 microg/l. In this study, we have compared these results with those obtained with a logistic regression model based on the determination of PSA and %fPSA. The diagnostic efficacy of the logistic regression model is greater than that of the currently used model. The posterior construction of a nomogram based on the data obtained greatly facilitates the application of the logistic regression model. Copyright Copyright 1999 S. Karger AG, Basel