R Molina

Hospital Clínic de Barcelona, Barcino, Catalonia, Spain

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Publications (112)366.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The usefulness of tumor markers in the differential diagnosis of cancer in patients with ascites remains a matter of controversy. Few studies have reported the measurement of cancer antigen 125 (CA125) and cytokeratin 19 soluble fragments (CYFRA21-1) in ascitic fluid. The aim of the present study was to evaluate the diagnostic accuracy of these tumor markers in the detection of malignant ascites. Materials and Methods: We analyzed CA125 and CYFRA21-1 from 143 consecutive undiagnosed patients with ascitis. Results: Use of CA125 gave a sensitivity of 39.7% and a specificity of 98.8%, and CYFRA21-1 a sensitivity of 50.0% and a specificity of 97.6% in differential diagnosis of malignant ascites. For combined use of CA125 plus CYFRA21-1, sensitivity was 65.5% and specificity 96.5%. In patients with negative cytology, these two tumor markers had a sensitivity of 50% and a specificity of 96.5%. Conclusion: The determination of tumor markers in ascitic fluid could be useful for the diagnostic assessment of patients with ascites.
    Anticancer research 10/2015; 35(10):5655-5660. · 1.83 Impact Factor
  • L Foj · X Filella · J Alcover · J M Augé · J M Escudero · R Molina ·
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    ABSTRACT: The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial assays has been suggested to be decreased by calibration to World Health Organization (WHO) reference materials. To characterize the current situation, it is necessary to know its impact in the critical cutoffs used in clinical practice. In the present study, we tested 167 samples with tPSA concentrations of 0 to 20 μg/L using seven PSA and six fPSA commercial assays, including Access, ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200, in which we only measured tPSA. tPSA and fPSA were measured in Access using the Hybritech and WHO calibrators. Passing-Bablok analysis was performed for PSA, and percentage of fPSA with the Hybritech-calibrated access comparison assay. For tPSA, relative differences were more than 10 % at 0.2 μg/L for ARCHITECT i2000, and at a critical concentration of 3, 4, and 10 μg/L, the relative difference was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at a critical concentration of 10 %, the 10 % relative difference limit was exceeded by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative difference limit. We have shown significant discordances between assays included in this study despite advances in standardization conducted in the last years. Further harmonization efforts are required in order to obtain a complete clinical concordance.
    Tumor Biology 10/2013; 35(3). DOI:10.1007/s13277-013-1249-2 · 3.61 Impact Factor
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    ABSTRACT: The utility of tumour markers (TM) in the differential diagnosis of cancer in serous effusion (fluid effusion (FE)) has been the subject of controversy. The aim of this study was to prospectively validate our previous study and to assess whether the addition of adenosine deaminase (ADA), C-reactive protein (CRP) or percentage of polymorphonuclear cells (%PN) allows the identification of false positives. In this study, carcinoembryonic antigen, cancer antigen 15-3, cancer antigen 19-9, ADA, CRP and %PN in FE were determined in 347 patients with 391 effusions. Effusions were considered as malignant effusion when at least one TM in serum exceeded the cutoff and the ratio FE/S was higher than 1.2. Also, cases with values of ADA, CRP and %PN above the established cutoffs in serous effusion were considered as potential false positives. The combined sensitivity and specificity of the three TM was 76.2 % (95 % confidence intervals (CI) 67.8-83.3 %) and 97.0 % (95 % CI 94.1-98.7), respectively. Subanalysis of the 318 cases with previous criteria and negative ADA, CRP and %PN obtained sensitivities of 78.4 % (95 % CI 69.4-85.6) and a specificity of 100 % (95 % CI 98.2-100). The results obtained validate our previous study and are improved with the addition of ADA, CRP and %PN. TM in serous effusions and serum could be useful for the diagnostic assessment of patients with serous effusions.
    Tumor Biology 06/2012; 33(5):1661-8. DOI:10.1007/s13277-012-0422-3 · 3.61 Impact Factor
  • Molina R · Auge JM ·

  • Auge JM · Molina R ·

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    ABSTRACT: 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 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. 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. High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.
    Annals of Oncology 02/2008; 19(2):269-75. DOI:10.1093/annonc/mdm490 · 7.04 Impact Factor
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    ABSTRACT: Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma. Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment. High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively). Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.
    Anticancer research 01/2007; 27(1B):595-9. · 1.83 Impact Factor

  • Annals of the New York Academy of Sciences 12/2006; 586(1):29 - 42. DOI:10.1111/j.1749-6632.1990.tb17786.x · 4.38 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor (VEGF) promotes normal and pathological angiogenesis. VEGF is a chemotactic factor for macrophages and vascular smooth muscle cells, and induces synthesis of metalloproteinases and adhesion molecules. VEGF expression is regulated by hypoxia, cytokines, oncogenes, and oxidized low-density lipoprotein (LDL). The purpose of this study was to determine the relationship between levels of lipid parameters and VEGF, to investigate whether pravastatin treatment influences VEGF serum concentrations, and to examine the relationship between VEGF and the variations in post-treatment lipid and inflammatory parameters. Eighteen patients aged 48+/-6.8 years with total cholesterol (TC) >6.1 mmol/L comprised the hypercholesterolemic group. The controls included 12 individuals aged 50+/-7.4 years with TC <5.1 mmol/L. TC, high-density lipoprotein cholesterol (HDLC), triglycerides, LDLC, C-reactive protein (CRP), and VEGF were determined in both groups at baseline, and in the hypercholesterolemic group after 4 months of treatment with 20 mg/day pravastatin. A significant correlation was observed between concentrations of VEGF and TC, LDLC and TG, and a significant difference in VEGF concentration was observed between the control group (mean 142 ng/L) and the hypercholesterolemic group (mean 272.9 ng/L). A significant decrease was observed in TC (14.7 %), LDLC (21.5 %), CRP (22.7 %), and VEGF (14.8 %) after 4 months of treatment with pravastatin. A relationship was found between serum levels of VEGF and most atherogenic lipoproteins. In patients with hypercholesterolemia treated with pravastatin, a reduction in VEGF and CRP was seen in addition to lipid decreases.
    Scandinavian Journal of Clinical and Laboratory Investigation 04/2006; 66(3):261-7. DOI:10.1080/00365510600564949 · 1.90 Impact Factor
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    ABSTRACT: To study the clinical value of the determination of serum S-100 protein as a single tumor marker or in combination with tyrosinase RT-PCR in patients with melanoma receiving adjuvant interferon. Patients were tested for serum S-100 protein luminoimmunometric assay and for blood tyrosinase mRNA (RT-PCR), before starting interferon and every 2-3 months thereafter. One hundred and six patients (stage IIA, 27; IIB, 19; III, 49; and IV, 11) were included in the study. Median follow-up was 51 months (range 2-76). In the univariate analysis, under treatment S-100 > or =0.15 microg/l and a positive RT-PCR correlated with a lower disease-free survival and overall survival (OS). In the multivariate analysis, clinical stage, under therapy positive RT-PCR and S-100 levels > or =0.15 mug/ml, were independent prognostic factors for OS. The hazard ratio for OS was 3.9 (95% CI, 1.67-9.15; p = 0.004) and 2.2 (95% CI, 1.05-4.6; p = 0.016) for S-100 > or =0.15 microg/l and positive RT-PCR, respectively. When both techniques where combined, a positive RT-PCR indicated a poorer clinical outcome only in patients with S-100 <0.15 microg/l. S-100 > or =0.15 microg/l and a positive RT-PCR during adjuvant interferon therapy indicate a high risk of death in resected melanoma patients. S-100 determination has a higher positive predictive value than RT-PCR, while tyrosinase RT-PCR adds prognostic information in patients with S-100 <0.15 microg/l.
    Oncology 08/2005; 68(4-6):341-9. DOI:10.1159/000086973 · 2.42 Impact Factor

  • Clinical Oncology 01/2005; 16(8):583-4. DOI:10.1016/j.clon.2004.08.004 · 3.40 Impact Factor
  • Jaume Trapé · Rafael Molina · Francesc Sant ·
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    ABSTRACT: We evaluated the diagnostic utility of simultaneous determination of 5 tumor markers, CEA, CA 125, CA 15-3, CA 19-9 and cytokeratin 19 (CYFRA 21-1), in fluid and serum from 101 patients, 52 with pleural effusion (22 malignant) and 49 patients with ascites (14 malignant). Tumor marker concentrations in fluid from patients with malignant effusions were significantly higher than those obtained in benign fluids or serum. However, there are two types of tumor markers: those released/secreted by normal mesothelia such as CA 125 and cytokeratin 19 (higher levels in benign fluids than in serum) and non-released/secreted tumor markers (low concentrations in benign fluids) such as CEA, CA 19-9 and CA 15-3. The fluid/serum (F/S) ratio showed better sensitivity with maximum specificity than a single determination in fluid for CEA, CA 15-3 and CA 19-9, but not for CA 125 and CYFRA. The combination of a F/S ratio greater than 1.2 and a cut-off of 5 ng/ml for CEA, 30 U/ml for CA 15-3 and 37 U/ml for CA 19-9 showed sensitivities of 58, 57 and 44%, respectively, and a specificity of 100%, with a combined sensitivity of 82% for overall effusions and 79% for fluids with negative cytology with a specificity of 100%. In conclusion, the use of the F/S ratio in nonsecreted tumor markers such as CEA, CA 19-9 and CA 15-3 improve the sensitivity and specificity and allow standardization of the cut-off.
    Tumor Biology 12/2004; 25(5-6):276-81. DOI:10.1159/000081392 · 3.61 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the effectiveness and toxicity of a new combination schedule based on concurrent navelbine, cisplatin and hyperfractionated radiotherapy in patients with locally advanced NSCLC treated with platinum and gemcitabine induction and consolidation chemotherapy. The 37 patients with pathological confirmed advanced NSCLC (non-surgical stages IIIA and IIIB) were included in the study. All of them were assessable for survival and 32 for response. The treatment schedule consisted of cisplatin (100 mg/m2) or carboplatin (400 mg/m2) on day 1 with gemcitabine (1000 mg/m2) on days 1, 8 and 15. Treatment was given every 28 days for two courses, followed by concurrent administration of accelerated modified hyperfractionated radiotherapy, with concomitant boost, with a total dose of 61.64 Gy administered for 5 weeks, with cisplatin and navelbine, for two courses, finally followed by two courses of the same initial chemotherapy. Four patients achieved complete response (12.5%) and 14 (44%) partial response, for an overall objective response rate of 56.5%. After a minimum follow-up duration of 35.5 months, median progression free survival was 12.2 months. The median survival was 15.4 months with actuarial 1-, 2- and 3-year survival of 67, 21 and 15%, respectively. The main toxicity was hematological. There was esophagitis (grades III and IV) in 30% of the patients and there were two treatment-related deaths. Combined treatment with concurrent radiotherapy and chemotherapy in non-surgical NSCLC is an acceptable treatment modality. However, the toxicity was not negligible.
    Lung Cancer 08/2004; 45(1):67-75. DOI:10.1016/j.lungcan.2003.12.012 · 3.96 Impact Factor
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    ABSTRACT: CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients with non-small cell lung cancer and compared with clinical parameters (age, sex, Karnofsky Index, symptoms and smoking status), histopathological parameters (stage, histology, tumor size and nodal involvement), biological parameters (LDH and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE: 22%. One of the tumor markers was abnormally high in 87% of the patients with locoregional disease and in 100% of the patients with metastases. Except for NSE, all tumor markers showed a clear relationship with tumor stage and histology and therefore enabled a better histological diagnosis. Abnormal CEA serum levels were mainly found in adenocarcinomas, CA 125 in large-cell lung cancers (LCLC) and adenocarcinomas and SCC in squamous tumors. Eighty-five percent of the patients with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%, respectively.
    Tumor Biology 12/2003; 24(4):209-218. DOI:10.1159/000074432 · 3.61 Impact Factor
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    ABSTRACT: Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value.
    Tumor Biology 11/2003; 24(3):156-164. DOI:10.1159/000073846 · 3.61 Impact Factor
  • R Molina · X Filella · G Zanon · J Pahisa · J Alicarte · M Munoz · B Farrus · A M Ballesta ·
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    ABSTRACT: Tumor markers were prospectively (CEA and CA 15.3) or retrospectively (c-erbB-2) studied in the sera of 503 untreated patients with breast cancer diagnosed from 1988 to 2001. Abnormal c-erbB-2 levels (> 15 U/ml) were found in 7%, CEA in 12% and CA 15.3 in 13% of the 503 patients. C-erbB-2 serum levels were only related to c-erbB-2 in tissue, with significantly higher concentrations in patients with positivity in tissue. All the tumor markers (c-erbB-2 only in patients with positivity in tissue) were correlated with tumor size, TNM and nodal involvement. CEA was also related to menopausal status, c-erbB-2 overexpression in tissue and ER. Univariate analysis (mean follow-up 8 years) showed that CEA and CA 15.3 were prognostic factors with significantly shorter disease-free survival (DFS) and overall survival (OS) in patients with pretreatment tumor marker positivity. Multivariate analysis in DFS and in OS showed that nodal involvement CEA and ER but not tumor size, menopausal status, histological grade, histology, CA 15.3, c-erbB-2, PgR, adjuvant treatment, p53 (345 patients) or c-erbB-2 in tissue are independent prognostic factors. In summary, tumor markers are a useful, inexpensive and reproducible tool for prognosis in breast cancer.
    Anticancer research 03/2003; 23(2A):1043-50. · 1.83 Impact Factor
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    ABSTRACT: The deleted GSTT1 and GSTM1 genotypes (null genotypes) resulting in loss of transferase activity are found in 10-20% and 50-60% of the population, respectively. The GSTT1- and GSTM1-dependent risk for sporadic colorectal cancer (CRC) was studied in 247 incident CRC cases and 296 hospital-based controls. The GSTT1-null genotype was found to be 1.5 times more prevalent in CRC patients (17.4%) compared with controls (11.1%) (crude OR 1.6; p = 0.03). The GSTM1-null genotype was found to be equally prevalent in cases and controls (53%). Multivariate analysis showed a significant 1.7-fold risk for CRC associated with the GSTT1-null genotypes (p = 0.04) and this increased to 2.9 for smokers (p = 0.02). This study provides evidence of gene-environment interaction and illustrates the importance of further research into the role of genetic susceptibility for CRC.
    Anticancer research 11/2002; 22(6A):3399-403. · 1.83 Impact Factor

  • Clinical Chemistry 01/2002; 47(12):2162-4. · 7.91 Impact Factor
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    ABSTRACT: Among urinary tumor markers we studied the utility of the BTA TRAK assay to diagnose transitional cell carcinoma of the bladder in highly suspiscious patients, in comparison to urine cytology. Materials and A preliminary study of 65 patients was made (21 transitional cell carcinoma (TCC), 36 without TCC and 8 excluded patients who received BCG therapy, endocavitary mytomicin or radiotherapy), using the BTA TRAK, cytology and cystoscopy. 12 out of the 21 selected patients were pTa (9 G1and 3 G2), 2 carcinoma in situ (CIS), 2pT1 (1 G2 and 1 G3) and 5 muscle invasive tumors (all of them G3). Setting our cut-off at 18 U/ml, a sensitivity of 52.3% and a specificity of 88.9% was reached. BTA TRAK detected 11 out of 21 of the tumors as well as urine cytology. However, BTA TRAK was more sensitive in the detection of low grade tumors (p<0.05). When considering both tests as complementary, a combined sensitivity of 80.9% and specificity of 88.5% were obtained. BTA TRAK is a valid test for the diagnosis of TCC of the bladder, which is not superior to urine cytology but complementary. More extensive prospective studies are required to validate this application and others of the BTA TRAK assay used either alone or in combination with urinary cytology in the management of bladder cancerpatients.
    Anticancer research 01/2002; 22(2B):1157-60. · 1.83 Impact Factor
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    ABSTRACT: HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.
    The Breast 02/2001; 10(1):67-77. DOI:10.1054/brst.2000.0225 · 2.38 Impact Factor

Publication Stats

3k Citations
366.05 Total Impact Points


  • 1991-2012
    • Hospital Clínic de Barcelona
      • • Servicio de Enfermedades Autoinmunes y Sistémicas
      • • Servicio de Hematología
      • • Servicio de Neurología
      Barcino, Catalonia, Spain
  • 1988-2008
    • University of Barcelona
      • • Department of Medicine
      • • Facultad de Medicina
      Barcino, Catalonia, Spain
  • 2003
    • Hospital Son Dureta
      Palma, Balearic Islands, Spain
  • 1995
    • Agència de Salut Pública de Barcelona
      Barcino, Catalonia, Spain
  • 1992
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 1990
    • Hospital Clínico, Maracaibo
      Maracaibo, Estado Zulia, Venezuela