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Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients
SIMPLE SUMMARY: Histological transformation remains the leading cause of death in patients diagnosed with follicular lymphoma (FL). To date, no clinical nor biological biomarkers have been identified to unequivocally predict patients in high risk of transformation. In this study, we investigated the...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909114/ https://www.ncbi.nlm.nih.gov/pubmed/35267625 http://dx.doi.org/10.3390/cancers14051316 |
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author | Enemark, Marie Beck Hybel, Trine Engelbrecht Madsen, Charlotte Lauridsen, Kristina Lystlund Honoré, Bent Plesner, Trine Lindhardt Hamilton-Dutoit, Stephen d’Amore, Francesco Ludvigsen, Maja |
author_facet | Enemark, Marie Beck Hybel, Trine Engelbrecht Madsen, Charlotte Lauridsen, Kristina Lystlund Honoré, Bent Plesner, Trine Lindhardt Hamilton-Dutoit, Stephen d’Amore, Francesco Ludvigsen, Maja |
author_sort | Enemark, Marie Beck |
collection | PubMed |
description | SIMPLE SUMMARY: Histological transformation remains the leading cause of death in patients diagnosed with follicular lymphoma (FL). To date, no clinical nor biological biomarkers have been identified to unequivocally predict patients in high risk of transformation. In this study, we investigated the predictive value of the hyaluronic acid receptors RHAMM and CD44. Expression levels of RHAMM were higher in patients with subsequent transformation and were associated with poorer outcome. ABSTRACT: Histological transformation (HT) remains the leading cause of mortality in follicular lymphoma (FL), underlining the need to identify reliable transformation predictors. The hyaluronic acid receptors CD44 and the receptor for hyaluronan mediated motility (RHAMM, also known as HMMR and CD168), have been shown to be involved in the pathogeneses of both solid tumors and hematological malignancies. In an attempt to improve risk stratification, expression of RHAMM and CD44 were evaluated by immunohistochemistry and digital image analysis in pre-therapeutic tumor-tissue biopsies from FL patients, either without (nt-FL, n = 34), or with (st-FL, n = 31) subsequent transformation, and in paired biopsies from the transformed lymphomas (tFL, n = 31). At the time of initial diagnosis, samples from st-FL patients had a higher expression of RHAMM compared with samples from nt-FL patients (p < 0.001). RHAMM expression further increased in tFL samples following transformation (p < 0.001). Evaluation of CD44 expression showed no differences in expression comparing nt-FL, st-FL, and tFL samples. Shorter transformation-free survival was associated with high tumoral and intrafollicular RHAMM expression, as well as with low intrafollicular CD44 expression (p = 0.002, p < 0.001, and p = 0.034, respectively). Our data suggest that high tumor-tissue RHAMM expression predicts the risk of shorter transformation-free survival in FL patients already at initial diagnosis. |
format | Online Article Text |
id | pubmed-8909114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89091142022-03-11 Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients Enemark, Marie Beck Hybel, Trine Engelbrecht Madsen, Charlotte Lauridsen, Kristina Lystlund Honoré, Bent Plesner, Trine Lindhardt Hamilton-Dutoit, Stephen d’Amore, Francesco Ludvigsen, Maja Cancers (Basel) Article SIMPLE SUMMARY: Histological transformation remains the leading cause of death in patients diagnosed with follicular lymphoma (FL). To date, no clinical nor biological biomarkers have been identified to unequivocally predict patients in high risk of transformation. In this study, we investigated the predictive value of the hyaluronic acid receptors RHAMM and CD44. Expression levels of RHAMM were higher in patients with subsequent transformation and were associated with poorer outcome. ABSTRACT: Histological transformation (HT) remains the leading cause of mortality in follicular lymphoma (FL), underlining the need to identify reliable transformation predictors. The hyaluronic acid receptors CD44 and the receptor for hyaluronan mediated motility (RHAMM, also known as HMMR and CD168), have been shown to be involved in the pathogeneses of both solid tumors and hematological malignancies. In an attempt to improve risk stratification, expression of RHAMM and CD44 were evaluated by immunohistochemistry and digital image analysis in pre-therapeutic tumor-tissue biopsies from FL patients, either without (nt-FL, n = 34), or with (st-FL, n = 31) subsequent transformation, and in paired biopsies from the transformed lymphomas (tFL, n = 31). At the time of initial diagnosis, samples from st-FL patients had a higher expression of RHAMM compared with samples from nt-FL patients (p < 0.001). RHAMM expression further increased in tFL samples following transformation (p < 0.001). Evaluation of CD44 expression showed no differences in expression comparing nt-FL, st-FL, and tFL samples. Shorter transformation-free survival was associated with high tumoral and intrafollicular RHAMM expression, as well as with low intrafollicular CD44 expression (p = 0.002, p < 0.001, and p = 0.034, respectively). Our data suggest that high tumor-tissue RHAMM expression predicts the risk of shorter transformation-free survival in FL patients already at initial diagnosis. MDPI 2022-03-04 /pmc/articles/PMC8909114/ /pubmed/35267625 http://dx.doi.org/10.3390/cancers14051316 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 Enemark, Marie Beck Hybel, Trine Engelbrecht Madsen, Charlotte Lauridsen, Kristina Lystlund Honoré, Bent Plesner, Trine Lindhardt Hamilton-Dutoit, Stephen d’Amore, Francesco Ludvigsen, Maja Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients |
title | Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients |
title_full | Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients |
title_fullStr | Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients |
title_full_unstemmed | Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients |
title_short | Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients |
title_sort | tumor-tissue expression of the hyaluronic acid receptor rhamm predicts histological transformation in follicular lymphoma patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909114/ https://www.ncbi.nlm.nih.gov/pubmed/35267625 http://dx.doi.org/10.3390/cancers14051316 |
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