Valor diagnóstico de la combinación de nueve marcadores tumorales en neoplasias

Muchos marcadores tumorales (MT) no son específicos a un tipo particular de cáncer y el nivel de uno de ellos puede aumentar como consecuencia de más de un tipo de cáncer, por lo que se utilizan en combinación para lograr mayor efectividad diagnóstica. Este trabajo se propone evaluar el valor diagnóstico de la combinación de nueve MT utilizados en diagnóstico de neoplasia tanto de forma individual como combinados. Se realizó un estudio retrospectivo entre enero 2013 y mayo de 2015 en el Laboratorio Clínico del Centro de Investigaciones Médico Quirúrgicas de La Habana a 100 pacientes con diagnóstico de cáncer o sospecha clínica de neoplasia oculta a quienes se les determinaron los marcadores tumorales: antígeno carbohidrato (CA) 19.9, CA 72.4, CA 125, CA 15.3, antígeno carcinoembrionario (CEA), componente de la citoqueratina 19 (Cyfra 21-1), gonadotropina coriónica (HCG), ferritina y antígeno prostático de superficie (PSA). En todos los MT se observó un incremento del valor de corte sobre el valor límite superior de referencia mayor al 8%. En conjunto, la sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo fueron de 23%, 99%, 96% y 51%, respectivamente. Para un valor de corte de 50 la especificidad y el VPP aumentaron a 99,6% y 97,5%, respectivamente. El uso de los 9 marcadores tumorales en conjunto mostró ser útil en el proceso de diagnóstico de pacientes con enfermedad neoplásica. Palabras clave: marcadores tumorales, CA 19.9, CA 72.4, CA 125, CA 15.3, CEA, Cyfra 21-1, HCG, Ferritina y PSA Abstract: Many tumor markers are not specific to a particular type of cancer and the level of one of them may increase as a result of more than one type of cancer, that’s why they are used in combination to achieve greater diagnostic effectiveness. This work aims to evaluate the diagnostic value of the combination of nine tumor markers commonly used in diagnosis of neoplasia both individually and in combination. A retrospective study from January 2013 to May 2015 was conducted at the Clinical Laboratory of the Center for Medical and Surgical Research in Havana, in 100 patients with cancer diagnosis or clinical suspicion of occult malignancy and to whom carbohydrate antigen (CA) 19.9, 72.4, CA 125, CA 15.3, carcinoembryonic antigen (CEA), component cytokeratin 19 (CYFRA 21-1), chorionic gonadotropin (HCG), ferritin and prostate surface antigen (PSA) tumor markers were identified. An increase of cutoff value above the upper limit reference value in all higher TM 8% was observed. Overall, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value were 23 %, 99 %, 96 % and 51 %, respectively. For a cut value of 50 specificity and PPV, they increased to 99.6% and 97.5%, respectively. The use of 9 tumor markers together showed to be useful in the process of diagnosing patients with neoplastic disease. Key words: tumor markers, CA 19.9, CA 72.4, CA 125, CA 15.3, CEA, Cyfra 21-1, HCG, Ferritina and PSA.

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Stability of Tumor Markers CA 19.9, CA 125, and CA 15.3 in Serum Obtained from Plain Tubes and Tubes Containing Thixotropic Gel Separator

Clinical Chemistry ◽

10.1093/clinchem/43.12.2430 ◽

1997 ◽

Vol 43 (12) ◽

pp. 2430-2431 ◽

Cited By ~ 6

Author(s):

Giuseppe Banfi ◽

Pierangela Parma ◽

Marina Pontillo

Keyword(s):

Tumor Markers ◽

Ca 125 ◽

Ca 15.3 ◽

Ca 19.9

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Serum Tumor Markers may Precede Instrumental Response to Chemotherapy in Patients with Metastatic Cancer

The International Journal of Biological Markers ◽

10.1177/172460080301800408 ◽

2003 ◽

Vol 18 (4) ◽

pp. 295-300 ◽

Cited By ~ 7

Author(s):

C. Massacesi ◽

M.B.L. Rocchi ◽

F. Marcucci ◽

A. Pilone ◽

M. Galeazzi ◽

...

Keyword(s):

Cancer Patients ◽

Tumor Markers ◽

Clinical Benefit ◽

Instrumental Response ◽

Metastatic Cancer ◽

Ca 125 ◽

Ca 15.3 ◽

Serum Tumor Markers ◽

Ca 19.9 ◽

Pain Improvement

Purpose Although serum tumor markers (STMs) are widely used in clinical practice, their predictive role for the response to anticancer treatment is still controversial. The correlation of CEA, CA 15.3, CA 19.9, CA 125 (only with peritoneal involvement) and NSE levels with imaging response and clinical benefit was investigated in 60 non-selected patients with metastatic epithelial cancers treated by single-agent docetaxel chemotherapy. Methods STM measurement was performed at baseline and subsequently every three to four weeks. We applied the WHO criteria to evaluate both STM and instrumental responses. Concordance analysis was performed by the Cohen Kw index, and the significance of the results was established using the Fleiss, Cohen & Everitt test. Qualitative interpretation of data was obtained with the Landis & Koch scale. Correlations of STM response with clinical benefit (PS or pain improvement) were evaluated by the chi-square test. Results The primary tumors included breast cancers (38 patients), gastrointestinal non-colorectal cancers (12 patients), and lung cancers (10 patients). An overall significant good degree of agreement was observed between STM and instrumental response (p<0.0005). The degree of agreement for each marker was as follows: excellent for CEA (p<0.0005) and CA 125 (p=0.006), good for CA 15.3 (p<0.0005) and CA 19.9 (p=0.011). Restricted analysis for the correlation of each marker with primary tumor origin showed good prediction of radiological response for CA 15.3 and CEA in breast cancer patients (p<0.0005 for both), for CEA and CA 19.9 in gastrointestinal cancer patients (p=0.01 and 0.04, respectively), and for CEA+NSE in lung cancer patients (p=0.01). Conversely, STM response did not correlate significantly with the clinical benefit for the patients, both in terms of PS and pain improvement (p=0.24 and p=0.42, respectively). Conclusion This study showed STMs to be good predictors of tumor response. Although STMs cannot replace diagnostic imaging, in metastatic cancer they might be useful to optimize the timing of radiological re-evaluation in the palliative setting.

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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

Tumor Biology ◽

10.1159/000181180 ◽

2008 ◽

Vol 29 (6) ◽

pp. 371-380 ◽

Cited By ~ 71

Author(s):

Rafael Molina ◽

Jose Maria Auge ◽

Jose Miguel Escudero ◽

Ramon Marrades ◽

Nuria Viñolas ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Markers ◽

Ca 125 ◽

Ca 15.3 ◽

Ca 19.9

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Pre-Treatment Prediction of Chemoresistance in Second-Line Chemotherapy of Ovarian Carcinoma: Value of Serological Tumor Marker Determination (Tetranectin, YKL-40, CASA, CA 125)

The International Journal of Biological Markers ◽

10.1177/172460080602100302 ◽

2006 ◽

Vol 21 (3) ◽

pp. 141-148 ◽

Cited By ~ 14

Author(s):

B. Gronlund ◽

E.V.S. Høgdall ◽

I.J. Christensen ◽

J.S. Johansen ◽

B. Nørgaard-Pedersen ◽

...

Keyword(s):

Logistic Regression ◽

Tumor Markers ◽

Predictive Value ◽

Serum Levels ◽

Ca 125 ◽

Second Line ◽

Second Line Chemotherapy ◽

Serological Tumor ◽

Line Chemotherapy

Objective To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. Methods From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed. Results At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2–0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0–3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2–2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66–0.91; p=0.001). Conclusion Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.

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Analytical Performance of Ca 19.9, Ca 125 and Ca 15.3 Assays as Observed through an External Quality Assessment Program

The International Journal of Biological Markers ◽

10.1177/172460089400900109 ◽

1994 ◽

Vol 9 (1) ◽

pp. 43-47 ◽

Cited By ~ 5

Author(s):

G.C. Zucchelli ◽

A. Pilo ◽

M.R. Chiesa ◽

S. Masini ◽

A. Clerico

Keyword(s):

Monoclonal Antibody ◽

Quality Control ◽

Quality Assessment ◽

External Quality Assessment ◽

Ca 125 ◽

External Quality ◽

Ca 15.3 ◽

Assessment Program ◽

Ca 19.9 ◽

Control Samples

Immunoassays of the tumor markers CA 19.9, CA125 and CA 15.3 are generally acknowledged to be a useful tool in the management of cancer patients. As a consequence, many methods developed by different companies are now commercially available. However, discrepancies have been described in the results of marker determinations even when the same monoclonal antibody was used. An external quality assessment (EQA) was carried out; starting from 1989 about 110 laboratories participated; since December 1991 the program was linked with the interlaboratory program Oncocheck organized by the Service de Radiopharmacie et Radioanalyse, University of Lyon. At present more than 200 laboratories of many European countries are involved: cumulatively 47 quality control samples have been prepared and sent to the participants. This manuscript is a report on data collected for CA 19.9, CA 125, and CA 15.3.

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Parameters of Blood Count and Tumor Markers in Patients with Borderline Ovarian Tumors: A Retrospective Analysis and Relation to Staging

ISRN Oncology ◽

10.5402/2012/947831 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Rosekeila Simões Nomelini ◽

Taísa Morete da Silva ◽

Beatriz Martins Tavares Murta ◽

Eddie Fernando Candido Murta

Keyword(s):

Tumor Markers ◽

Blood Count ◽

Ovarian Tumors ◽

Ca 125 ◽

Borderline Ovarian Tumor ◽

Tumor Type ◽

Borderline Ovarian Tumors ◽

Stage Ib ◽

Ca 19.9 ◽

Stage Ia

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n=13) and stage IB-IIIC (n=8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P<0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

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Within- and between-subject biological variation data for tumor markers based on the European Biological Variation Study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0283 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Abdurrahman Coşkun ◽

Aasne K. Aarsand ◽

Sverre Sandberg ◽

Elena Guerra ◽

Massimo Locatelli ◽

...

Keyword(s):

Tumor Markers ◽

Biological Variation ◽

Ca 125 ◽

Cytokeratin 19 ◽

Homogeneity Analysis ◽

Human Epididymis Protein 4 ◽

Corrected Data ◽

Index Of Individuality ◽

Monitoring Treatment ◽

Cytokeratin 19 Fragment

Abstract Objectives Reliable biological variation (BV) data are required for the clinical use of tumor markers in the diagnosis and monitoring of treatment effects in cancer. The European Biological Variation Study (EuBIVAS) was established by the EFLM Biological Variation Working Group to deliver BV data for clinically important measurands. In this study, EuBIVAS-based BV estimates are provided for cancer antigen (CA) 125, CA 15-3, CA 19-9, carcinoembryonic antigen, cytokeratin-19 fragment, alpha‐fetoprotein and human epididymis protein 4. Methods Subjects from five European countries were enrolled in the study, and weekly samples were collected from 91 healthy individuals (53 females and 38 males; 21–69 years old) for 10 consecutive weeks. All samples were analyzed in duplicate within a single run. After excluding outliers and homogeneity analysis, the BVs of tumor markers were determined by CV-ANOVA on trend-corrected data, when relevant (Røraas method). Results Marked individuality was found for all tumor markers. CYFRA 21-1 was the measurand with the highest index of individuality (II) at 0.67, whereas CA 19-9 had the lowest II at 0.07. The CV I s of HE4, CYFRA 21-1, CA 19-9, CA 125 and CA 15-3 of pre- and postmenopausal females were significantly different from each other. Conclusions This study provides updated BV estimates for several tumor markers, and the findings indicate that marked individuality is characteristic. The use of reference change values should be considered when monitoring treatment of patients by means of tumor markers.

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Dosage des marqueurs tumoraux ACE, CA 15.3, CA 125 et CA 19.9 dans les liquides dˈépanchement et le LCR par immunoanalyse en phase homogène. Corrélation avec les résultats cytologiques et les concentrations sériques

Immuno-analyse & Biologie Spécialisée ◽

10.1016/s0923-2532(02)01162-6 ◽

2002 ◽

Vol 17 (1) ◽

pp. 18-25 ◽

Cited By ~ 2

Author(s):

S Guepratte ◽

C Pallud ◽

M.F Pichon

Keyword(s):

Ca 125 ◽

Ca 15.3 ◽

Ca 19.9 ◽

Marqueurs Tumoraux

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Falsely Elevated CA 15-3 Levels in Ovarian Sarcoidosis with Peritoneal Involvement and Ascites

Case Reports in Obstetrics and Gynecology ◽

10.1155/2018/2039730 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3

Author(s):

Sotirios Tsiodras ◽

Alina-Roxani Gouloumi ◽

Zoi Tsakiraki ◽

George Chrelias ◽

Charalambos Chrelias ◽

...

Keyword(s):

Rare Case ◽

Clinical Laboratory ◽

Ca 125 ◽

Ovarian Malignancy ◽

Radiological Evaluation ◽

Ca 15.3

A rare case of ovarian sarcoidosis with peritoneal and omental involvement presenting as an ovarian malignancy is presented. Clinical, laboratory, and radiological evaluation of the patient revealed ascites and high levels of serum CA 125 and CA 15.3. The diagnosis of sarcoidosis was confirmed with pathology findings on tissues obtained during surgical laparotomy. Establishing the diagnosis of sarcoidosis can be treacherous and was complicated in this case by the falsely elevated biomarkers and ascites.

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