University of Oulu

Siria A Lemma, Milla Kuusisto, Kirsi-Maria Haapasaari, Raija Sormunen, Tuula Lehtinen, Tuula Klaavuniemi, Mine Eray, Esa Jantunen, Ylermi Soini, Kaija Vasala, Jan Böhm, Niina Salokorpi, Petri Koivunen, Peeter Karihtala, Jussi Vuoristo, Taina Turpeenniemi-Hujanen, Outi Kuittinen; Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma, Carcinogenesis, Volume 38, Issue 8, 1 August 2017, Pages 812–820, https://doi.org/10.1093/carcin/bgx061

Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma

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Author: Lemma, Siria A.1,2; Kuusisto, Milla1,2; Haapasaari, Kirsi-Maria1,2,3;
Organizations: 1Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland
2Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland
3Department of Pathology, Institute of Diagnostics, Medical Research Center Oulu, Oulu University Hospital, Kajaanintie 50, 90220 Oulu, Finland
4Biocenter Oulu, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland
5Department of Oncology, Tampere University Hospital, Teiskontie 35, 33521 Tampere, Finland
6Department of Oncology and Radiotherapy, Central Finland Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, Finland
7Department of Pathology, FIMLAB, Tampere University Hospital, Teiskontie 35, 33521 Tampere, Finland
8Department of Medicine, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland
9Department of Clinical Pathology and Forensic Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Puijonlaaksontie 2, 70210 Kuopio, Finland
10Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio, Finland
11Department of Pathology, Central Finland Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, Finland
12Department of Neurosurgery, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland
13Department of Otorhinolaryngology, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 55 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2017101050004
Language: English
Published: Oxford University Press, 2017
Publish Date: 2017-10-10
Description:

Abstract

Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses. The expression levels of ITGA10, CD44, PTEN, cadherin-11, CDH12, N-cadherin, P-cadherin, lactoferrin and E-cadherin were studied with IHC and IEM. GEP was performed to see whether found expressional changes are regulated at DNA/RNA level. IHC included 96 samples of primary CNS lymphoma (PCNSL), secondary CNS lymphoma (sCNSL) and systemic DLBCL (sDLBCL). IEM included two PCNSL, one sCNSL, one sDLBCL and one reactive lymph node samples. GEP was performed on two DLBCL samples, one with and one without CNS relapse. CNS disease was associated with enhanced expression of cytoplasmic and membranous ITGA10 and nuclear PTEN (P < 0.0005, P = 0.002, P = 0.024, respectively). sCNSL presented decreased membranous CD44 and nuclear and cytoplasmic cadherin-11 expressions (P = 0.001, P = 0.006, P = 0.048, respectively). In PCNSL lactoferrin expression was upregulated (P < 0.0005). IEM results were mainly supportive of the IHC results. In GEP CD44, cadherin-11, lactoferrin and E-cadherin were under-expressed in CNS disease. Our results are in line with previous studies, where gene expressions in extracellular matrix and adhesion-related pathways are altered in CNS lymphoma. This study gives new information on the DLBCL CNS tropism. If further verified, these markers might become useful in predicting CNS relapses.

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Series: Carcinogenesis
ISSN: 0143-3334
ISSN-E: 1460-2180
ISSN-L: 0143-3334
Volume: 38
Issue: 8
Pages: 812 - 820
DOI: 10.1093/carcin/bgx061
OADOI: https://oadoi.org/10.1093/carcin/bgx061
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This study was supported by grants from the Cancer Society of Northern Finland, Orion-Farmos Research Foundation, the Finnish Medical Society Duodecim, Finnish Cultural Foundation and the Väisänen Fund in Terttu Foundation.
Copyright information: © The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
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