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Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christoph / Zettl, Uwe K.


IMPACT FACTOR 2017: 0.216

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2567-9449
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Volume 39, Issue 2

Issues

Improved diagnosis of mesothelioma by a combination of soluble mesothelin-related peptide and CYFRA 21-1

Verbesserte Diagnostik des Mesothelioms durch die Kombination von löslichem Mesothelin Related Peptide und CYFRA 21-1

Stefan Holdenrieder
  • Corresponding author
  • Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rudolf Hatz / Judith Reinmiedl / Karin Hofmann / Andreas Schalhorn / Petra Stieber
  • Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Munich, Germany
  • Oncology Outpatient Speciality Center Elisenhof Munich, Munich, Germany
  • Other articles by this author:
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Published Online: 2015-04-09 | DOI: https://doi.org/10.1515/labmed-2015-0032

Abstract

Background: Soluble mesothelin-related peptide (sMRP) has shown great potential for malignant mesothelioma detection. However, data on comparison with other cancer and benign diseases as well as with other established lung cancer biomarkers are rare.

Methods: In this study, SMRP was investigated in sera from 1506 individuals including 147 healthy donors, 285 patients with diverse benign diseases and 1074 patients with mesothelioma (n=39) and various malignant tumors (lung, gastrointestinal, gynecological, urological). For differential diagnosis of lung diseases, carcinoembryonic antigen, cytokeratin 19-fragments (CYFRA 21-1), neuron-specific enolase and squamous cell cancer antigen were determined additionally.

Results: Ninety-fifth percentiles of sMRP serum levels in healthy persons were 1.2 nM, in patients with benign diseases between 2.0 and 3.8 nM and in cancer patients between 1.5 and 44.3 nM. Highest values were observed in mesothelioma (median 2.3 nM; 95th percentile 44.3 nM). When differential diagnostic capacity of cancer detection vs. the relevant benign control group was tested, sMRP showed best results for mesothelioma and ovarian cancer with a sensitivity of 45% and 37%, respectively, at 95% specificity. At 100% specificity vs. normal controls, sensitivity for mesothelioma detection was found to be 59% for sMRP, 73% for CYFRA 21-1 and 88% for the combination of both. At 95% specificity vs. all other lung diseases, sensitivity for mesothelioma was 48% for sMRP, 15% for CYFRA 21-1 and 46% for the combination of both.

Conclusions: In summary, SMRP is a valuable serum biomarker that is specific at high concentrations for the detection of malignant mesothelioma. For screening purposes, the combination with CYFRA 21-1 improves the sensitivity at high specificity.

Zusammenfassung

Hintergrund: Das lösliche Mesothelin Related Peptide (sMRP) zeigt großes Potential für die Detektion von malignen Mesotheliomen. Jedoch sind wenige Daten zum Vergleich mit anderen Tumorarten und benignen Erkrankungen wie auch mit anderen etablierten Biomarkern des Lungenkarzinoms verfügbar.

Methoden: In dieser Studie wurde sMRP in Sera von 1506 Personen untersucht, darunter 147 gesunde Kontrollpersonen, 285 Patienten mit unterschiedlichen benignen Erkrankungen und 1047 Patienten mit malignem Mesotheliom (n=39) und verschiedenen weiteren malignen Tumorerkrankungen (Lunge, gastrointestinale, gynäkologische, urologische). Zur Differentialdiagnose von Lungenerkrankungen wurden zusätzlich das carcinoembryonale Antigen, Cytokeratin 19-Fragmente (CYFRA 21-1), die Neuronen-spezifische Enolase und das Squamous Cell Cancer Antigen bestimmt.

Ergebnisse: Die 95. Perzentile der sMRP-Serumwerte bei gesunden Personen war 1.2 nM, bei Patienten mit benignen Erkrankungen zwischen 2.0 und 3.8 nM und bei Patienten mit einer Tumorerkrankung zwischen 1.5 und 44.3 nM. Die höchsten Werte wurden beim Mesotheliom beobachtet (Median 2.3 nM; 95. Perzentile 44.3 nM). Bei der Untersuchung des Potentials für die Differentialdiagnose von Tumoren und den relevanten benignen Erkrankungen zeigte sMRP die besten Ergebnisse für das Mesotheliom und das Ovarialkarzinom mit Sensitivitäten von 45% und 37% bei einer 95% Spezifität. Bei 100% Spezifität gegenüber gesunden Kontrollpersonen war die Sensitivität für die Erkennung eines Mesothelioms bei 59% für sMRP, 73% für CYFRA 21-1 und 88% für die Kombination der beiden Marker. Bei 95% Spezifität gegenüber allen anderen Lungenerkrankungen war die Sensitivität für das Mesotheliom 48% für sMRP, 15% für CYFRA 21-1 und 46% für die Kombination der beiden Marker.

Schlussfolgerungen: SMRP ist ein wertvoller Serum-Biomarker, welcher in hohen Konzentrationen das maligne Mesotheliom spezifisch erkennt. Beim Screening verbessert die Kombination mit CYFRA 21-1 die Sensitivität bei hoher Spezifität.

Reviewed publication

HoldenriederS.

Keywords: CYFRA 21-1; diagnosis; mesothelin; mesothelioma; serum

Schlüsselwörter:: CYFRA 21-1; Diagnose; Mesothelin; Mesotheliom; Serum

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About the article

Correspondence: Stefan Holdenrieder, Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany, Phone: +49-228-287-12126, Fax: +49-228-287-12159, E-Mail:


Accepted: 2015-03-12

Published Online: 2015-04-09

Published in Print: 2015-04-01


Citation Information: LaboratoriumsMedizin, Volume 39, Issue 2, Pages 103–113, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2015-0032.

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