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New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study

Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach t...

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Autores principales: Angeloni, Antonio, De Vito, Corrado, Farina, Antonella, Terracciano, Daniela, Cennamo, Michele, Passerini, Rita, Bottari, Fabio, Schirinzi, Annalisa, Vettori, Roberto, Steffan, Agostino, Mais, Valerio, Coghe, Ferdinando, Della Corte, Luigi, Bifulco, Giuseppe, Baccolini, Valentina, Berardelli, Elena, Migliara, Giuseppe, Anastasi, Emanuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000204/
https://www.ncbi.nlm.nih.gov/pubmed/35407605
http://dx.doi.org/10.3390/jcm11071994
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author Angeloni, Antonio
De Vito, Corrado
Farina, Antonella
Terracciano, Daniela
Cennamo, Michele
Passerini, Rita
Bottari, Fabio
Schirinzi, Annalisa
Vettori, Roberto
Steffan, Agostino
Mais, Valerio
Coghe, Ferdinando
Della Corte, Luigi
Bifulco, Giuseppe
Baccolini, Valentina
Berardelli, Elena
Migliara, Giuseppe
Anastasi, Emanuela
author_facet Angeloni, Antonio
De Vito, Corrado
Farina, Antonella
Terracciano, Daniela
Cennamo, Michele
Passerini, Rita
Bottari, Fabio
Schirinzi, Annalisa
Vettori, Roberto
Steffan, Agostino
Mais, Valerio
Coghe, Ferdinando
Della Corte, Luigi
Bifulco, Giuseppe
Baccolini, Valentina
Berardelli, Elena
Migliara, Giuseppe
Anastasi, Emanuela
author_sort Angeloni, Antonio
collection PubMed
description Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A two-sided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in post-menopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools.
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spelling pubmed-90002042022-04-12 New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study Angeloni, Antonio De Vito, Corrado Farina, Antonella Terracciano, Daniela Cennamo, Michele Passerini, Rita Bottari, Fabio Schirinzi, Annalisa Vettori, Roberto Steffan, Agostino Mais, Valerio Coghe, Ferdinando Della Corte, Luigi Bifulco, Giuseppe Baccolini, Valentina Berardelli, Elena Migliara, Giuseppe Anastasi, Emanuela J Clin Med Article Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A two-sided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in post-menopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools. MDPI 2022-04-02 /pmc/articles/PMC9000204/ /pubmed/35407605 http://dx.doi.org/10.3390/jcm11071994 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Angeloni, Antonio
De Vito, Corrado
Farina, Antonella
Terracciano, Daniela
Cennamo, Michele
Passerini, Rita
Bottari, Fabio
Schirinzi, Annalisa
Vettori, Roberto
Steffan, Agostino
Mais, Valerio
Coghe, Ferdinando
Della Corte, Luigi
Bifulco, Giuseppe
Baccolini, Valentina
Berardelli, Elena
Migliara, Giuseppe
Anastasi, Emanuela
New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
title New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
title_full New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
title_fullStr New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
title_full_unstemmed New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
title_short New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
title_sort new analytical approach for the alignment of different he4 automated immunometric systems: an italian multicentric study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000204/
https://www.ncbi.nlm.nih.gov/pubmed/35407605
http://dx.doi.org/10.3390/jcm11071994
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