General Use

The program is based on the experience of Dr. Molina in the study of tumor markers during the last 25 years. It has two complementary but related parts:

First part is the application of the criteria and experience learned to differentiate the main problem of tumor markers, specificity. Most markers present increases in various benign diseases, often indistinguishable from cases with tumors. In the routine of the hospital, more than 65% of the results of positive markers are false increases, due to intercurrent non-neoplastic diseases.The incorrect assessment of these data affect and increase the anxiety of doctor and patient, because of the performance and repetition of complementary explorations, mainly radiological and numerous visits. This explains why many doctors do not trust their results and distrust their clinical application. The program incorporates criteria and experience that allow suggesting the existence of a false positive in most cases, obtaining very high specificities, higher than 99%. In summary, the program allows the use of tumor markers with a variable sensitivity according to stage, neoplasia and marker, but with high specificity. Evaluates the known markers in the majority of epithelial neoplasms, being applicable in all cases of suspicion of one of these tumors.

The second part of the program uses tumor markers as diagnostic elements of neoplasia. It identifies concentrations of different markers that it indicates with high specificity, 99%, neoplasia. It identifies concentrations of different markers that it indicates with high specificity, 99%, neoplasia. The sensitivity varies depending on the type of tumor, marker and stage. In locally advanced or metastatic neoplasias, it is globally 75%, reaching 85% in cases with metastasis. In more than 70% of the cases with positive tumor markers, it is possible to suggest the origin of the tumor, or at least to focus on a reduced number of options. It also allows and helps in the differential diagnosis of metastasis or suspicion of non-epithelial neoplasms, such as myeloma, brain tumors, or mesenchymal tumors. The main utility is to suggest the risk of cancer and the origin in patients with paraneoplastic syndromes (constitutional syndrome, deep vein thrombosis), images in various locations (brain, liver, bone, lung, etc.) before pleural or ascitic effusions and in patients with cancer of unknown origin (COD). The main utility is to suggest the risk of cancer and the origin in patients with paraneoplastic syndromes (constitutional syndrome, deep vein thrombosis), images in various locations (brain, liver, bone, lung, etc.) before pleural or ascitic effusions and in patients with cancer of unknown origin (COD). This last group of patients includes about 50-70 cases of patients who come with proven metastasis, but after performing the possible diagnostic techniques, the origin of the tumor was unknown, in many cases even after the autopsy of the patient.

The program allows to guide the existence of cancer in 85% of these cases and suggest an origin in 65% of cases with positive tumor markers. The algorithm incorporates the monitoring of therapeutic response through the serial evaluation of markers and the study of criteria to assess the response in an early and cost-effective way. Using this information, the clinical team would be allowed to know the response to the treatment chosen during the first two months of initiation, which is a great advantage in relation to the radiographic evaluation, which is performed later and spaced in the weather. Therefore, not only can the lack of response in terms of efficacy be assessed early, but the exposure to toxicity from ineffective therapies should be eliminated and the search for new treatments should be anticipated in cases with a lack of response. These data are particularly important in cases of COD, where the origin of the tumor is unknown, making it more difficult to decide the appropriate therapies and evaluate their response. This should have a clear favorable impact on patient survival and quality of life during clinical follow-up thanks to the elimination of toxicity problems to treatments that will not provide any efficacy. These results will be perfectly validated in relation to the usual radiological evaluation criteria, RECIST v1.1: if there is response, progression or stabilization of the disease. The patients included in the study are preferably the clinical routine of the Hospital Clinic, but there have been collaborations from other Spanish, European and Asian centers. This collaboration with other centers, allows to avoid the possible bias of results of multicenter studies.

The variability between the information of the analytical results, the incorporation of the differences in the numerical concordance between them and their possible influence on the approach to the diagnosis through the study of tumor markers has also been evaluated.

Objectives:

Assist in the correct assessment of tumor markers, using criteria that distinguish the benign or malignant origin of a result.
Assessment of internal factors (technical: hemolysis, manufacturer, etc.) or external factors (patient situation, treatments, etc.) that influence the outcome of tumor markers. This assessment will be for the inclusion of user information (systemic dermatological diseases) or for the incorporation of quantitative biochemical criteria to assess the influence of liver function (Gammaglutamyltranspeptidase, transaminases, bilirubin) or renal (creatinine or glomerular filtration), subdivided into function of ethnicity, age and gender.
Establishment of the risk of neoplasia in the general population or in patients with signs or symptoms of suspicion of neoplasia such as paraneoplastic syndromes (constitutional syndrome, deep vein thrombosis, dermatomyositis, etc.), nodules or images (bony, pulmonary, hepatic, cerebral, ganglionic , etc.).
Helps in the differential diagnosis with non-epithelial neoplasms, mesenchymal (brain tumors, mesothelioma, sarcomas, etc.) or hematological (leukemias, lymphomas, etc.).
It helps in the diagnosis and etiological diagnosis in patients with cancer of unknown origin.
As a final objective we have the assessment of the response, taking in consideration the type of treatment, the period of time elapsed, the number of chemotherapy cycles and the change in the results obtained. Validating the results with the radiological result with the RECIST.

BIBLIOGRAPHY

Most of the scientific publications of Dr. Molina, could be associated to the learning applied in said algorithm. The main one, the use of markers in neoplasms of unknown origin, is attached.

Duffy M, Harbeck N, Nap M, Molina R. Nicolini A, Senkus E, Cardoso F. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers. Europ J Cancer 2017, 75: 284-298.

Sölétormos G, Duffy MJ, Othman S, Verheijen RHM, Tholander B, Bast Jr RC, Gaarenstroom KN, Sturgeon CM, Bonfrer H, Hyltoft Petersen P, Troonen H, Torre GC, Kulpa J, Tuxen MK, Molina R Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer: Updated Guidelines from The European Group on Tumor Markers (EGTM).. Int J Gynecol Cancer 2016;26: 43-51)

Molina R, Marrades RM, Augé JM, Escudero JM, Viñolas N, Reguart N, Ramirez J, Filella X, Molins L, Agusti A.Assessment of a Combined Panel of Six Serum Tumor Markers for Lung Cancer.Am J Respir Crit Care Med. 2015 Oct 14. [Epub ahead of print

Catharina M. Korse, Stefan Holdenrieder, Xiu-yi Zhi, Xiaotong Zhang d, Ling Qiud, Andrea Geistanger,Marcus-Rene Lisy, Birgit Wehnl, Daan van den Broek, José M. Escudero, Jens Standopb, Mu Hu, Rafael Molina. Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China. Clinica Chimica Acta 438 (2015) 388–395

Duffy MJ, Sturgeon CM, Sölétormos G, Barak V, Molina R, Hayes DF, Diamandis EP, Bossuyt PM. Validation of new cancer biomarkers: a position statement from the European group on tumor markers.Clin Chem. 2015 Jun;61(6):809-20. doi: 10.1373/clinchem.2015.239863. Epub 2015 Apr 16. Review

Trapé J, Gurt G, Franquesa J, Montesinos J, Arnau A, Sala M, Sant F, Casado E, Ordeig JM, Bergos C, Vida F, Sort P, Isava Á, González M, Molina R.Diagnostic Accuracy of Tumor Markers CYFRA21-1 and CA125 in the Differential Diagnosis of Ascites..Anticancer Res. 2015 Oct;35(10):5655-60.

Auge JM, Pellise M, Escudero JM, Hernandez C, Andreu M, Grau J, Buron A, López-Cerón M, Bessa X, Serradesanferm A, Piracés M, Macià F, Guayta R, Filella X, Molina R, Jimenez W, Castells A; PROCOLON Group. Risk stratification for advanced colorectal neoplasia according to fecal hemoglobin concentration in a colorectal cancer screening program. Gastroenterology. 2014 Sep;147(3):628-636

Filella X, Foj L, Alcover J, Augé JM, Molina R, Jiménez W The influence of prostate volume in prostate health index performance in patients with total PSA lower than 10 μg/L.Clin Chim Acta. 2014 Sep 25;436:303-7. doi: 10.1016/j.cca.2014.06.019. Epub 2014 Jun 27

Filella X, Foj L, Augé JM, Molina R, Alcover J Clinical utility of %p2PSA and prostate health index in the detection of prostate cancer.Clin Chem Lab Med. 2014 Sep;52(9):1347-55. doi: 10.1515/cclm-2014-0027

Foj L, Filella X, Alcover J, Augé JM, Escudero JM, Molina R.Variability of assay methods for total and free PSA after WHO standardization.Tumour Biol. 2014 Mar;35(3):1867-73. doi: 10.1007/s13277-013-1249-2. Epub 2013 Oct 4.

Filella X, Alcover J, Molina R. Active surveillance in prostate cancer: the need to standardize. Tumour Biol. 2011 Oct;32(5):839-43.

Auge JM¹, Rodriguez C, Pellise M, Bernal A, Grau J, Castells A, Filella X, Molina R.Analytical and clinical performance of Kroma iT, a compact fully-automated immunochemistry analyzer for fecal occult hemoglobin. Anticancer Res. 2013 Dec;33(12):5633-7.

Molina R, Bosch X, Augé JM, Filella X, Escudero JM, Molina V, Solé M, López-Soto A. Utility of serum tumor markers as an aid in the differential diagnosis of patients w ith clinical suspicion of cancer and in patients w ith cancer of unknow n primary site. Tumour Biol. 2012 Apr;33(2):463-74. PMID: 22161237 [PubMed - indexed for MEDLINE]

Trapé J, Molina R, Sant F, Montesinos J, Arnau A, Franquesa J, Blavia R, Martín E, Marquilles E, Perich D, Pérez C, Roca JM, Doménech M, López J, Badal JM. Diagnostic accuracy of tumour markers in serous effusions: a validation study. Tumour Biol. 2012 Oct;33(5):1661-8. PMID: 22678976 [PubMed - indexed for MEDLINE]

Molina R, Alvarez E, Aniel Quiroga A, Borque M, Candas B, Leon A, Poyatos RM, Gelabert M. Evaluation of chromogranin A determined by three different procedures in patients with benign diseases, neuroendocrine tumors and other malignancies. Tumor Biol 2011; 32:13-22

Molina R, Escudero JM, Muñoz M, Augé JM, Filella X. Circulating Levels of HER-2/neu Oncoprotein in Breast Cancer. Clinical Chemistry and Laboratory Medicine 2011;50 (1): 5–21.

Escudero JM, Auge JM, Filella X, Torne A,, Pahisa J, Molina R The utility of serum Human Epididymis protein (HE4) in patients with malignant and non malignant diseases: comparison with CA 125. Clin Chem 2011 Nov;57(11):1534-44.

Molina R, Escudero JM, Auge JM, Filella X, Foj L, Torne A, Lejarcegui,L, Pahisa J, HE-4 a novel tumor marker for ovarian cancer: comparison with CA 125 in patients with gynecological diseases. Tumor Biol 2011 Dec;32(6):1087-95..

Molina R, Auge JM, Farrus B, Zanong G, Pahisa J, Muñoz M, Torne A, Filella X, Escudero JM, Fernadez P, Velasco M. Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer.Clin Chem 2010; 56:1148-1157.

Molina V, Visa L, Conill C, Navarro S, Escudero JM, Auge JM, Filella X, Lopez-Boado MA, Ferrer J, Fernández-Cruz L, Molina R. CA 19–9 in pancreatic cancer: retrospectiv e ev aluation of patients w ith suspicion of pancreatic cancer. Tumour Biol. 201133:799-807

Molina R, Auge JM, Escudero J, Filella X, Zanon G, Pahisa J, Farrus B, Muñoz M, Velasco M. Evaluation of tumor markers (HER-2/neu oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer: prognostic value. Tumor Biol 2010, 131: 171-180.

Molina R, Holdenreider S, Auge JM, Schalhorn A, Hatz R, Stieber P. Diagnostic relevance of circulating biomarkers in patients with lung cancer. Cancer BioMark 2010; 6:163-178. (Review).

Alcover J, Filella X, Luque P, Molina R, Izquierdo L, Auge JM, Alcaraz A. Prognostic value of IL-6 in localized prostatic cancer. Anticancer Res 2010; 10:4369-4372.

Molina R, Auge JM, Bosch X, Escudero JM, Vinolas N, Marrades R et al. Usefulness of serum tumor markers, including progastrin-releasing peptide, in patients with lung cancer: correlation with histology. Tumour Biol 2009;30:121-9.

Vidal O, Metges JP, Elizalde I, Valentini M, Volant A, Molina R et al. High preoperative serum vascular endothelial growth factor levels predict poor clinical outcome after curative resection of gastric cancer. Br J Surg 2009;96:1443-51.

van Dalen A, Favier J, Hallensleben E, Burges A, Stieber P, de Bruijn HW, Fink D, Ferrero A, McGing P, Harlozinska A, Kainz Ch, Markowska J, Molina R, Sturgeon C, Bowman A, Einarsson R, Goike H. Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up. Eur J Gynaecol Oncol.2009;30(6):609-15. PubMed PMID: 20099488.

R. Molina, M. Gion. A Gressner, F Troalen, JM Auge, S Holdenrieder, M Zancan, M Wycislo, P. Stieber. Alternative antibody for the detection of CA 15.3 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access BR Monitor assay on the UniCel DxI 800 Immunoassay systemClin Chem Lab Med 2008, 46: 612-622.

P. Stieber, R. Molina, M. Gion. A Gressner, F Troalen, S Holdenrieder, JM Auge , M Zancan, M Wycislo, V. Jarrige. Alternative antibody for the detection of CA 19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access GI Monitor assay on the UniCel DxI 800 Immunoassay system. Clin Chem Lab Med 2008, 46: 600-611

S Holdenrieder, R. Molina, M. Gion. A Gressner, F Troalen, JM Auge , M Zancan, M Wycislo, P. Sieber. Alternative antibody for the detection of CA 125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access OV Monitor assay on the UniCel DxI 800 Immunoassay system. Clin Chem Lab Med 2008, 46: 589-599

Molina R, Auge JM, Escudero JM, Marrades R, Vinolas N, Carcereny E et al. Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE. Tumour Biol 2008;29:371-80.

Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC Jr, 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; National Academy of Clinical Biochemistry.National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.Clin Chem 2008, 54: 11-79.

Molina R, Barak V, van Dalen A, Duffy MJ, Einarsson R, Gion M, Goike H, Lamerz R, Nap M, Döletormos G, Stieber P. Tumor markers in breast cancer. European Group on Tumor Markers (EGTM) recommendations. Internal Medicine, 2007-2008, 15-16: 31-32.

Domingo-Domenech J, Fernandez PL, Filella X, Martinez-Fernandez A, Molina R, Fernandez E, Alcaraz A, Codony J, Gascon P, Mellado B.Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel.Ann Oncol. 2008 Feb;19(2):269-75. Epub 2007 Nov 12.

Filella X, Alcover J, Molina R, Luque P, Corral JM, Augé JM, Coca F.Usefulness of proprostate-specific antigen in the diagnosis of prostate cancer.Anticancer Res. 2007 Jan-Feb;27(1B):607-10

M. Gonzalez Cao, JM Auge, R. Molina, R. Marti, C. Carrea, T. Castel, R. Vilella, C. Conill, M. Sanchez, J Malvehy, S. Puig. Melanoma Inhibotory Activity Protein (MIA), Beta-2 microglobulin and Lactate Dehydrogenase (LDH) in Metastatic Melanoma. Anticancer Res 2007, 27:595-600.

Domingo-Domènech J, Castel T, Auge JM, Garcia-Albeniz XA, Conill C, Puig S, Vilella R, Matas J, Malvehy J, Gascón P, Mellado B, Molina R.Prognostic implications of protein S-100beta serum levels in the clinical outcome of high-risk melanoma patients.Tumour Biol. 2007;28(5):264-72. Epub 2007 Oct 26. PMID: 17962723 [PubMed - indexed for MEDLINE]

J. Maurel, C. Nadal, X. Garcia-Albeniz, R. Gallego, E. Carcereny, V. Almendro, M. Marmol, E. Gallardo, JM Auge, R Longaron, A. Martinez-Fernandez, R. Molina, A. Castells, P. Gascon. Serum Matrix Metalloprotease 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer 2007, 121: 1066-1071.

Caballero M, Grau JJ, Blanch JL, Domingo-Domenech J, Auge JM, Jimenez W, Bernal-Sprekelsen M. Serum vascular endothelial growth factor as a predictive factor in metronomic (weekly) Paclitaxel treatment for advanced head and neck cancer. Arch Otolaryngol Head Neck Surg. 2007 Nov;133(11):1143-8. PubMed PMID:18025320.

Stieber P, Hatz R, Holdenrieder S, Molina R, Nap M, von Pawel J, Schalhorn A, Schneider J, Yamaguchi K. National Academy of Clinical Biochemistry Guidelines for the use of tumor markers in lung cancer. In NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic - Lung Cancer (Section 3P). 2006; published online at www.nacb.org/lmpg/ tumor_LMPG_draft_PDF.stm

Molina R, Auge JM, Filella X, Vinolas N, Alicarte J, Domingo JM, BallestaAM. Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer. Anticancer Res. 2005 May-Jun;25(3A):1773-8. PMID: 16033098 [PubMed - indexed for MEDLINE]

Auge JM, Molina R, Filella X, Bosch E, Gonzalez Cao M, Puig S, Malvehy J, Castel T, Ballesta AM. S-100beta and MIA in advanced melanoma in relation to prognostic factors.Anticancer Res. 2005 May-Jun;25(3A):1779-82. PMID: 16033099 [PubMed - indexed for MEDLINE]

Molina R, Barak V, van Dalen A, Duffy MJ, Einarsson R, Gion M, Goike H, Lamerz R, Nap M, Soletormos G, Stieber P. Tumor markers in breast cancer- European Group on Tumor Markersrecommendations.Tumour Biol. 2005 Nov-Dec;26(6):281-93. Review.

PMID: 16254457 [PubMed - indexed for MEDLINE]

Nadal C, Maurel J, Gallego R, Castells A, Longarón R, Marmol M, Sanz S, Molina R, Martin-Richard M, Gascón P.FAS/FAS ligand ratio: a marker of oxaliplatin-based intrinsic and acquired resistance in advanced colorectal cancer.Clin Cancer Res. 2005 Jul 1;11(13):4770-4.

Molina R, Filella X, Auge JM, Bosch E, Torne A, Pahisa J, Lejarcegui JA, Rovirosa A, Mellado B, Ordi J, Biete A. CYFRA 21.1 in patients with cervical cancer: comparison with SCC and CEA. Anticancer Res. 2005 May-Jun;25(3A):1765-71. PMID: 16033097 [PubMed - indexed for MEDLINE]

Domingo-Domenech J, Molina R, Castel T, Montagut C, Puig S, Conill C, Marti R, Vera M, Auge JM, Malvehy J, Grau JJ, Gascon P, Mellado B. Serum protein s-100 predicts clinical outcome in patients with melanoma treated with adjuvant interferon--comparison with tyrosinase rt-PCR.Oncology. 2005;68(4-6):341-9. Epub 2005 Jul 11. PMID: 16020961 [PubMed - indexed for MEDLINE]

Trape J, Molina R, Sant F. Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions. Tumour Biol. 2004 Sep-Dec;25(5-6):276-81. PMID: 15627892 [PubMed - indexed for MEDLINE]

Fuentes R, Bover I, Rifa J, Moreno V, Canals E, Marquez A, Barreiro E, Borras J, Molina R, Viladiu P. Factors influencing survival in a prospective cohort of patients with non-small cell lung cancer: an updated assessment.Clin Oncol (R Coll Radiol). 2004 Dec;16(8):583-4. No abstract available. PMID: 15630857 [PubMed - indexed for MEDLINE]

Filella X, Truan D, Alcover J, Gutierrez R, Molina R, Coca F, Ballesta AM. Complexed prostate-specific antigen for the detection of prostate cancer.Anticancer Res. 2004 Nov-Dec;24(6):4181-5. PMID: 15736470 [PubMed - indexed for MEDLINE]

Filella X, Truan D, Alcover J, Quinto L, Molina R, Luque P, Coca F, Ballesta AM. Comparison of several combinations of free, complexed, and total PSA in thediagnosis of prostate cancer in patients with urologic symptoms.Urology. 2004 Jun;63(6):1100-3; discussion 1103-4. PMID: 15183958 [PubMed - indexed for MEDLINE]

Filella X, Truan D, Alcover J, Molina R, Luque P, Coca F, Ballesta AM. [Usefulness of PSA and its fractions in the diagnosis of prostate cancer].Med Clin (Barc). 2004 Feb 28;122(7):241-4. Spanish. PMID: 15012870 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Auge JM. ProGRP: a new biomarker for small cell lung cancer.Clin Biochem. 2004 Jul;37(7):505-11. Review. PMID: 15234231 [PubMed - indexed for MEDLINE]

Molina R, Auge JM, Alicarte J, Filella X, Vinolas N, Ballesta AM. Pro-gastrin-releasing peptide in patients with benign and malignant diseases.Tumour Biol. 2004 Jan-Apr;25(1-2):56-61. PMID: 15192313 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Zanon G, Pahisa J, Alicarte J, Munoz M, Farrus B, Ballesta AM.

Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer.Anticancer Res. 2003 Mar-Apr;23(2A):1043-50.

Molina R, Filella X, Lejarcegui JA, Pahisa J, Torne A, Rovirosa A, Mellado B, Ordi J, Puig-Tintore LM, Alicarte J, Biete A, Iglesias J. Prospective evaluation of squamous cell carcinoma and carcinoembryonic antigen as prognostic factors in patients with cervical cancer.Tumour Biol. 2003 May-Jun;24(3):156-64. PMID: 14610320 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Alicarte J, Zanon G, Pahisa J, Munoz M, Farrus B, Ballesta AM.

Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer.

Anticancer Res. 2003 Mar-Apr;23(2A):1035-41. PMID: 12820344 [PubMed - in process]

Molina R, Filella X, Auge JM, Fuentes R, Bover I, Rifa J, Moreno V, Canals E, Vinolas N, Marquez A, Barreiro E, Borras J, Viladiu P. Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparisonwith the main clinical and pathological prognostic factors.Tumour Biol. 2003 Aug-Sep;24(4):209-18. PMID: 14654716 [PubMed - indexed for MEDLINE]

Molina R, Navarro J, Filella X, Castel T, Ballesta AM. S-100 protein serum levels in patients with benign and malignant diseases: false-positive results related to liver and renal function.Tumour Biol. 2002 Jan-Feb;23(1):39-44. PMID: 11893905 [PubMed - indexed for MEDLINE

Filella X, Alcover J, Corral JM, Molina R, Beardo P, Ballesta AM. Free to complexed PSA ratio in differentiating benign prostate hyperplasia from prostate cancer.Anticancer Res. 2001 Sep-Oct;21(5):3717-20. PMID: 11848550 [PubMed - indexed for MEDLINE]

Filella X, Alcover J, Molina R, Corral JM, Carretero P, Ballesta AM. Measurement of complexed PSA in the differential diagnosis between prostate cancer and benign prostate hyperplasia.Prostate. 2000 Feb 15;42(3):181-5. PMID: 10639188 [PubMed - indexed for MEDLINE]

Van Dalen A, Favier J, Baumgartner L, Hasholzner U, De Bruijn H, Dobbler D, Dombi VH, Fink D, Giai M, McGing P, Harlozinska A, Kainz C, Markowska J, Molina R, Sturgeon C, Bowman A, Einarsson R. Serum levels of CA 125 and TPS during treatment of ovarian cancer.Anticancer Res. 2000 Nov-Dec;20(6D):5107-8. PMID: 11326677 [PubMed - indexed for MEDLINE]

Van Dalen A, Favier J, Burges A, Hasholzner U, de Bruijn HW, Dobler-Girdziunaite D, Dombi VH, Fink D, Giai M, McGing P, Harlozinska A, Kainz C, Markowska J, Molina R, Sturgeon C, Bowman A, Einarsson R. Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.Gynecol Oncol. 2000 Dec;79(3):444-50. PMID: 11104617 [PubMed - indexed for MEDLINE]

Van Dalen A, Favier J, Baumgartner L, Hasholzner U, de Bruijn H, Dobbler D, Dombi VH, Fink D, Giai M, McGing P, Harlozinska A, Kainz C, Markowska J, Molina R, Sturgeon C, Einarsson R. Prognostic significance of CA 125 and TPS levels after chemotherapy in ovarian cancer patients.Anticancer Res. 1999 Jul-Aug;19(4A):2523-6. PMID: 10470187 [PubMed - indexed for MEDLINE]

Molina R, Farrus B, Filella X, Jo J, Zanon G, Pahisa J, Latre M, Munoz M, Ballesta AM.

Carcinoembryonic antigen in tissue and serum from breast cancer patients relationship with steroid receptors and clinical applications in the prognosis and early diagnosis of relapse.Anticancer Res. 1999 Jul-Aug;19(4A):2557-62. PMID: 10470194 [PubMed - indexed for MEDLINE]

Molina R, Jo J, Filella X, Zanon G, Farrus B, Munoz M, Latre ML, Pahisa J, Velasco M, Fernandez P, Estape J, Ballesta AM. C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients. Anticancer Res. 1999 Jul-Aug;19(4A):2551-5. PMID: 10470193 [PubMed - indexed for MEDLINE]

Filella X, Alcover J, Quinto L, Molina R, Bosch-Capblanch X, Carretero P, Ballesta AM. Evaluation of a multivariate prostate-specific antigen and percentage of free prostate-specific antigen logistic regression model in the diagnosis of prostate cancer. Tumour Biol. 1999 Nov-Dec;20(6):312-8. PMID: 10567877 [PubMed - indexed for MEDLINE]

Vinolas N, Molina R, Galan MC, Casas F, Callejas MA, Filella X, Grau JJ, Ballesta AM, Estape J. Tumor markers in response monitoring and prognosis of non-small cell lung cancer: preliminary report.Anticancer Res. 1998 Jan-Feb;18(1B):631-4. PMID: 584045 [PubMed - indexed for MEDLINE]

Van Dalen A, Barak V, Cremaschi A, Gion M, Molina R, Namer M, Stieber P, Sturgeon C, Einarsson R. The prognostic significance of increasing marker levels in metastatic breast cancer patients with clinically complete remission, partial remission or stable disease.Int J Biol Markers. 1998 Jan-Mar;13(1):10-5. PMID: 9681294 [PubMed - indexed for MEDLINE]

Molina R, Segui MA, Climent MA, Bellmunt J, Albanelll J, Fernandez M, Filella X, Jo J, Gimenez N, Iglesias E, Miralles M, Alonso C, Peiro G, Perez-Picanol E, Ballesta AM. p53 oncoprotein as a prognostic indicator in patients with breast cancer. Anticancer Res. 1998 Jan-Feb;18(1B):507-11. PMID: 9580543 [PubMed - indexed for MEDLINE]

* Molina R, Jo J, Filella X, Zanon G, Pahisa J, Munoz M, Farrus B, Latre ML, Escriche C, Estape J, Ballesta AM. c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value.Breast Cancer Res Treat. 1998 Sep;51(2):109-19. PMID: 9879773 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Jo J, Agusti C, Ballesta AM. CA 125 in biological fluids. Int J Biol Markers. 1998 Oct-Dec;13(4):224-30. Review. PMID: 10228906 [PubMed - indexed for MEDLINE]

Molina R, Jo J, Filella X, Bruix J, Castells A, Hague M, Ballesta AM. Serum levels of C-erbB-2 (HER-2/neu) in patients with malignant and non-malignant diseases. Tumour Biol. 1997;18(3):188-96. PMID: 9143415 [PubMed - indexed for MEDLINE]

Filella X, Alcover J, Molina R, Rodriguez A, Carretero P, Ballesta AM. Free and total PSA in the diagnosis of prostate cancer.Tumour Biol. 1997;18(6):332-40. PMID: 9372866 [PubMed - indexed for MEDLINE]

* Filella X, Alcover J, Molina R, Rodriguez A, Carretero P, Ballesta AM. Clinical evaluation of free PSA/total PSA (prostate-specific antigen) ratio in the diagnosis of prostate cancer.Eur J Cancer. 1997 Jul;33(8):1226-9. PMID: 9301447 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Alcover J, Carretero P, Ballesta AM. Detection of nonprostatic PSA in serum and nonserum samples from women. Int J Cancer. 1996 Nov 15;68(4):424-7. PMID: 8945610 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Alcover J, Menendez V, Gimenez N, Jo J, Carretero P, Ballesta AM. Prostate-specific antigen detection by ultrasensitive assay in samples from women.Prostate. 1996 Nov;29(5):311-6. PMID: 8899004 [PubMed - indexed for MEDLINE]

* Filella X, Molina R, Ballesta AM, Gil MJ, Allepuz C, Rioja LA. Value of PSA (prostate-specific antigen) in the detection of prostate cancer in patients with urological symptoms. Results of a multicentre study.Eur J Cancer. 1996 Jun;32A(7):1125-8. PMID: 8758241 [PubMed - indexed for MEDLINE]

Filella X, Alcover J, Molina R, Carrere W, Carretero P, Ballesta AM. Usefulness of prostate-specific antigen density as a diagnostic test of prostate cancer. Tumour Biol. 1996;17(1):20-6. PMID: 7501969 [PubMed - indexed for MEDLINE

Molina R, Torres MD, Moragas M, Perez-Villa J, Filella X, Jo J, Farrus B, Gimenez N, Traserra J, Ballesta AM. Prognostic significance of SCC antigen in the serum of patients with head andneck cancer.Tumour Biol. 1996;17(2):81-9. PMID: 8658017 [PubMed - indexed for MEDLINE]

Novell F, Trias M, Molina R, Filella X. Detection of occult liver metastases in colorectal cancer by measurement of biliary carcinoembryonic antigen.Anticancer Res. 1997 Jul-ug;17(4A):2743-6. PMID: 9252708 [PubMed - indexed for MEDLINE]

Molina R, Jo J, Zanon G, Filella X, Farrus B, Munoz M, Latre ML, Pahisa J, Velasco M, Fernandez P, Estape J, Ballesta AM. Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3.Br J Cancer. 1996 Oct;74(7):1126-31. PMID: 8855986 [PubMed - indexed for MEDLINE]

Molina R, Jo J, Filella X, Zanon G, Pahisa J, Munoz M, Farrus B, Latre ML, Gimenez N, Hage M, Estape J, Ballesta AM. C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis.Anticancer Res. 1996 Jul-Aug;16(4B):2295-300. PMID: 8694559 [PubMed - indexed for MEDLINE]

Albanell J, Bellmunt J, Molina R, Garcia M, Caragol I, Bermejo B, Ribas A, Carulla J, Gallego OS, Espanol T, Sole Calvo LA. Node-negative breast cancers with p53(-)/HER2-neu(-) status may identify women with very good prognosis. Anticancer Res. 1996 Mar-Apr;16(2):1027-32. PMID: 8687094 [PubMed - indexed for MEDLINE]

Molina R, Zanon G, Filella X, Moreno F, Jo J, Daniels M, Latre ML, Gimenez N, Pahisa J, Velasco M, et al. Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients.Breast Cancer Res Treat. 1995;36(1):41-8. PMID: 7579505 [PubMed - indexed for MEDLINE]

Ballesta AM, Molina R, Filella X, Jo J, Gimenez N. Carcinoembryonic antigen in staging and follow-up of patients with solid tumors.Tumour Biol. 1995;16(1):32-41. Review. PMID: 7863220 [PubMed - indexed for MEDLINE]

Borras G, Molina R, Xercavins J, Ballesta A, Iglesias J. Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix.Gynecol Oncol. 1995 May;57(2):205-11. PMID: 7729735 [PubMed - indexed for MEDLINE]

Filella X, Alcover J, Molina R, Gimenez N, Rodriguez A, Jo J, Carretero P, Ballesta AM. Clinical usefulness of free PSA fraction as an indicator of prostate cancer.Int J Cancer. 1995 Dec 11;63(6):780-4. PMID: 8847133 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Alcover J, Casals E, Carmona F, Ballesta AM. Prostate specific antigen in non-serum samples from women.Int J Biol Markers. 1995 Oct-Dec;10(4):238-9. No abstract available. PMID: 8750653 [PubMed - indexed for MEDLINE]

Alcover J, Filella J, Vendrell JR, Molina R, Ballesta AM, Carretero P. [The diagnostic utility of PSA density]Actas Urol Esp. 1995 Mar;19(3):192-5. Spanish. PMID: 8659275 [PubMed - indexed for MEDLINE]

Molina R, Torres MD, Moragas M, Filella X, Jo J, Gimenez N, Traserra J, Ballesta AM.

Prognostic value of TPS in patients with head and neck malignancies: comparison with SCC.Anticancer Res. 1995 Mar-Apr;15(2):479-84. PMID: 7763026 [PubMed - indexed for MEDLINE]

Molina R, Agusti C, Filella X, Jo J, Joseph J, Gimenez N, Ballesta AM. Study of a new tumor marker, CYFRA 21-1, in malignant and nonmalignantdiseases.Tumour Biol. 1994;15(6):318-25. PMID: 7997803 [PubMed - indexed for MEDLINE]

Molina R, Agusti C, Mane JM, Filella X, Jo J, Joseph J, Gimenez N, Estape J, Ballesta AM. CYFRA 21-1 in lung cancer: comparison with CEA, CA 125, SCC and NSE serum levels.Int J Biol Markers. 1994 Apr-Jun;9(2):96-101. PMID: 7523548 [PubMed - indexed for MEDLINE]

Molina R, Agusti C, Filella X, Jo J, Joseph J, Gimenez N, Ballesta AM. Study of a new tumor marker, CYFRA 21-1, in malignant and nonmalignant diseases.Tumour Biol. 1994;15(6):318-25. PMID: 7997803 [PubMed - indexed for MEDLINE]

Filella X, Fuster J, Molina R, Grau JJ, Garcia-Valdecasas JC, Grande L, Estape J, Ballesta AM. TAG-72, CA 19.9 and CEA as tumor markers in gastric cancer.Acta Oncol. 1994;33(7):747-51. PMID: 7993641 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Pique JM, Grau JJ, Garcia-Valdecasas JC, Biete A, Novell F, Astudillo E, Bordas JM, Campo E, et al. CEA as a prognostic factor in colorectal cancer.Anticancer Res. 1994 Mar-Apr;14(2B):705-8. PMID: 8010730 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Pique JM, Garcia-Valdecasas JC, Grau JJ, Novell F, Astudillo E, de Lacy A, Daniels M, Ballesta AM. Use of CA 19-9 in the early detection of recurrences in colorectal cancer: comparison with CEA.Tumour Biol. 1994;15(1):1-6. PMID: 8146525 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Segui MA, Climent MA, Perez-Picanol E, Alonso C, Jo J, Ojeda B, Tandon AK, Ballesta AM. Oncogenic proteins and prognostic correlations in breast cancer.In Vivo. 1993 Nov-Dec;7(6B):585-9. Review. No abstract available. PMID: 7910764 [PubMed - indexed for MEDLINE]

Alcover J, Filella X, Barranco MA, Molina R, Ballesta AM, Carretero P. False positive values of PAP and PSA in complicated and non-complicated benign prostatic hypertrophy.Arch Ital Urol Androl. 1993 Dec;65(6):657-60. PMID: 7508792 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Jo J, Bedini JL, Joseph J, Ballesta AM. Tumor associated glycoprotein-72 (TAG-72) levels in patients with non-malignant and malignant disease.Bull Cancer. 1992;79(3):271-7. Review. PMID: 1392166 [PubMed - indexed for MEDLINE]

Molina R, Ojeda B, Filella X, Borras G, Jo J, Mas E, Lopez JJ, Ballesta A. A prospective study of tumor markers CA 125 and CA 19.9 in patients with epithelial ovarian carcinomas.Tumour Biol. 1992;13(5-6):278-86. PMID: 1290025 [PubMed - indexed for MEDLINE]

Molina R, Ciocca DR, Tandon AK, Allred DC, Clark GM, Chamness GC, Gullick WJ, McGuire WL. Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques.Anticancer Res. 1992 Nov-Dec;12(6B):1965-71. PMID: 1363511 [PubMed - indexed for MEDLINE]

Allred DC, Clark GM, Molina R, Tandon AK, Schnitt SJ, Gilchrist KW, Osborne

CK, Tormey DC, McGuire WL. Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol. 1992 Sep;23(9):974-9. PMID: 1355464 [PubMed - indexed for MEDLINE]

Allred DC, Clark GM, Tandon AK, Molina R, Tormey DC, Osborne CK, Gilchrist KW, Mansour EG, Abeloff M, Eudey L, et al. HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.J Clin Oncol. 1992 Apr;10(4):599-605. PMID: 1548522 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Grau JJ, Pique JM, Garcia-Valdecasas JC, Astudillo E, Biete A, Bordas JM, Novell A, Campo E.Prognostic value of CA 19.9 levels in colorectal cancer.Ann Surg. 1992 Jul;216(1):55-9. PMID: 1632702 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Bruix J, Mengual P, Bosch J, Calvet X, Jo J, Ballesta AM. Cancer antigen 125 in serum and ascitic fluid of patients with liver diseases.Clin Chem. 1991 Aug;37(8):1379-83. PMID: 1868598 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Mengual PJ, Jo J, Ballesta AM. Significance of CA72.4 in patients with colorectal cancer. Comparison with CEA and CA19.9.J Nucl Biol Med. 1991 Jul-Sep;35(3):158-61. PMID: 1816871 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Mengual P, Prats M, Zanon G, Daniels M, Ballesta AM. MCA in patients with breast cancer: correlation with CEA and CA15-3. Int J Biol Markers. 1990 Jan-Mar;5(1):14-21. PMID: 2230347 [PubMed - indexed for MEDLINE]

Molina R, Filella X, Torres MD, Ballesta AM, Mengual P, Cases A, Balague A. SCC antigen measured in malignant and nonmalignant diseases.Clin Chem. 1990 Feb;36(2):251-4. PMID: 2302769 [PubMed - indexed for MEDLINE]

Filella X, Molina R, Bedini JL, Jo J, Joseph J, Ballesta AM. Clinical usefulness of CEA as tumor marker in patients with colorectal cancer. J Nucl Med Allied Sci. 1990 Oct-Dec;34(4 Suppl):107-10. No abstract available. PMID: 2092102 [PubMed - indexed for MEDLINE]

Molina R, Santabarbara P, Filella X, Mengual P, Ballesta AM, Balague A. Relationship of CA 125 and CA 19.9 with lung carcinoma histological subtype: preliminary study.

Int J Biol Markers. 1989 Oct-Dec;4(4):215-20.PMID: 2560789 [PubMed - indexed for MEDLINE]

Ballesta AM, Molina R. [Tumor markers and primary cancer of the liver]Med Clin (Barc). 1989 Sep 16;93(7):256-8. Review. Spanish. No abstract available. PMID: 2554076 [PubMed - indexed for MEDLINE]

Ballesta AM, Calvet X, Filella X, Bruix J, Bru C, Molina R, Rodes J. Alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma.J Nucl Med Allied Sci. 1989 Jul-Sep;33(3 Suppl):39-41. PMID: 2480420 [PubMed - indexed for MEDLINE]