Clinical Evaluation of the Simultaneous Determination of Tumor Markers in Fluid and Serum and Their Ratio in the Differential Diagnosis of Serous Effusions

Trapé, Jaume; Molina, Rafael; Sant, Francesc

doi:10.1159/000081392

Cited by 46 publications

(12 citation statements)

References 19 publications

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“…With CYFRA21-1,, Porcel et al [8] sought high specificity (100%) and obtained a sensitivity of 25% with a cut-off point of 175 μg/L with positive likelihood ratio (LHR+) >9999 and negative likelihood ratio (LHR-) of 0.75, Cynowska et al [9] sought high sensitivity (90.9%) and obtained a specificity of 7.7% with a cut-off point of 3.3 μg/L with LHR+ of 0.98 and LHR- of 1.18; finally, Korczynski et al [10], seeking high diagnostic accuracy, obtained a sensitivity of 41.7% and a specificity of 92.1% with a cut-off point of 74.7 μg/L LHR+ of 5.28 and LHR- of 0.63. Likewise, cut-off points ranging between 6.5 and 275 μg/L have been proposed for CEA in order to obtain maximum specificity [20–26]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of two strategies for the interpretation of tumour markers in pleural effusions

et al. 2017

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BackgroundPleural effusions present a diagnostic challenge. Approximately 20% are associated with cancer and some 50% require invasive procedures to perform diagnosis. Determination of tumour markers may help to identify patients with malignant effusions. Two strategies are used to obtain high specificity in the differential diagnosis of malignant pleural effusions: a) high cut-off, and b) fluid/serum (F/S) ratio and low cut-off. The aim of this study is to compare these two strategies and to establish whether the identification of possible false positives using benign biomarkers – ADA, CRP and % of polymorphonuclear cells – improves diagnostic accuracy.MethodsWe studied 402 pleural effusions, 122 of them malignant. Benign biomarkers were determined in pleural fluid, and CEA, CA72-4, CA19-9 and CA15-3 in pleural fluid and serum.ResultsEstablishing a cut-off value for each TM for a specificity of 100%, a joint sensitivity of 66.5% was obtained. With the F/S strategy and low cut-off points, sensitivity was 77% and specificity 98.2%, Subclassifying cases with negative benign biomarkers, both strategies achieved a specificity of 100%; sensitivity was 69.9% for single determination and 80.6% for F/S ratio.ConclusionsThe best interpretation of TM in the differential diagnosis of malignant pleural effusions is obtained using the F/S ratio in the group with negative benign biomarkers.

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confidence: 99%

Evaluation of two strategies for the interpretation of tumour markers in pleural effusions

et al. 2017

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“…Abnormal serum levels of CA 125 may be found in several benign and malignant diseases other than ovarian cancer [2, 4–6, 13–22]. Despite these issues, CA 125 is used to differentiate benign from malignant pelvic masses and is used as a prognostic factor in the early diagnosis of recurrence or to assess response to treatment [11–13, 15, 16, 32].…”

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confidence: 99%

“…Abnormal CA 125 serum levels can be found in malignancies of different origin including epithelial (endometrial, endocervix and lung cancer) and non-epithelial malignancies (lymphomas) [4–6, 13–21]. Abnormal CA 125 serum levels may be also found in several benign diseases, mainly those with effusions, liver or renal failure and benign gynaecological conditions (ovarian cysts, myomas and endometriosis) [4, 6, 13–22]. Sensitivity of CA 125 in ovarian cancer is related to tumour stage, with abnormal CA 125 serum levels in approximately 50% of stage I patients and 80–90% in patients of stages III–IV [2, 4–6, 11–16].…”

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HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases

Molina¹,

Escudero²,

Augé³

et al. 2011

Tumor Biol.

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The aim of this study is to evaluate a new tumour marker, HE4, in comparison with CA 125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in healthy women and in patients with benign and malignant gynaecological diseases. CA 125 and HE4 serum levels were determined in 66 healthy women, 285 patients with benign gynaecological diseases (68 endometriosis, 56 myomas, 137 ovarian cysts and 24 with other diseases), 33 patients with non-active gynaecological cancer and 143 with active gynaecological cancer (111 ovarian cancers). CA 125 and HE4 cut-offs were 35 U/mL and 150 pmol/L, respectively. ROMA algorithm cut-off was 13.1 and 27.7 for premenopausal or postmenopausal women, respectively. HE4, CA 125 and ROMA results were abnormal in 1.5%, 13.6% and 25.8% of healthy women and in 1.1%, 30.2% and 12.3% of patients with benign diseases, respectively. Among patients with cancer, HE4 (in contrast to CA 125) had significantly higher concentrations in ovarian cancer than in other malignancies (p < 0.001). Tumour marker sensitivity in ovarian cancer was 79.3% for HE4, 82.9% for CA 125 and 90.1% for ROMA. Both tumour markers, HE4 and CA 125 were related to tumour stage and histological type, with the lowest concentrations in mucinous tumours. A significantly higher area under the ROC curve was obtained with ROMA and HE4 than with CA 125 in the differential diagnosis of benign gynaecological diseases versus malignant ovarian cancer (0.952, 0.936 and 0.853, respectively). Data from our population indicate that ROMA algorithm might be further improved if it is used only in patients with normal HE4 and abnormal CA 125 serum levels (cancer risk for this profile is 44.4%). ROMA algorithm in HE4 positive had a similar sensitivity and only increases the specificity by 3.2% compared to HE4 alone.

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“…In a recent study using this strategy we found similar sensitivities for CEA, CA15-3, CA19-9 and Cancer antigen 72-4 (CA72-4) in pleural effusion (20). This strategy is less accurate for tumor markers secreted by mesothelial cells, such as cancer antigen 125 (CA125) and cytokeratin 19 fragments (CYFRA 21-1) that are best interpreted with a single determination in fluid effusion (21,22).…”

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Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions

Trapé

Sant

Montesinos

et al. 2020

In Vivo

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Background/Aim: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cutoff and ii) fluid/serum ratio (F/S) and low cutoff. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). Patients and Methods: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. Results: The strategy of high cutoff showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cutoff and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. Conclusion: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid. Ascites is the abnormal accumulation of fluid in the peritoneal cavity. It is mostly seen in patients with liver disease, pancreatic disease, tuberculous peritonitis, congestive heart failure, kidney disease, acquired immune deficiency syndrome and cancer (1). Cytology is the gold standard for confirming the presence of malignant cells in ascitic fluid, but its sensitivity only ranges between 50 and 70% (2). The main cause of this low sensitivity is the fact that a primary tumor may infiltrate the peritoneum but may not shed cells, with a negative result in the cytological analysis. In these cases, other invasive procedures, such as laparoscopy may be needed to confirm the presence of malignant cells. The potential of tumor markers (TM) for improving the diagnosis of malignant pleural and peritoneal effusions has been mentioned by several authors but there are major discrepancies between the reports regarding their specificity and sensitivity, and also in terms of the cutoff values used (3-5): for Carcinoembryonic antigen (CEA) the range is 2-50 ng/ml and for Cancer antigen 19-9 (CA19-9) it is 14.5-200 ku/l (6-10). Their sensitivity ranges between 24% and 77% and their specificity from 82% to 100% (6-10).

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Clinical Evaluation of the Simultaneous Determination of Tumor Markers in Fluid and Serum and Their Ratio in the Differential Diagnosis of Serous Effusions

Cited by 46 publications

References 19 publications

Evaluation of two strategies for the interpretation of tumour markers in pleural effusions

Evaluation of two strategies for the interpretation of tumour markers in pleural effusions

HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases

Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions

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