GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers

Sylvia Hartmann, Claudio Agostinelli, Jürgen Diener, Claudia Döring, Stefano Fanti, Pier L. Zinzani, Andrea Gallamini, Lothar Bergmann, Stefano Pileri, Martin Leo Hansmann

Research output: Contribution to journalArticle

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Abstract

Background: Increased glycolytic activity is a hallmark of cancer, allowing staging and restaging with 18F-fluorodeoxyglucose-positron-emission-tomography (PET). Since interim-PET is an important prognostic tool in Hodgkin lymphoma (HL), the aim of this study was to investigate the expression of proteins involved in the regulation of glucose metabolism in the different HL subtypes and their impact on clinical outcome.Methods: Lymph node biopsies from 54 HL cases and reactive lymphoid tissue were stained for glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and lactate exporter proteins MCT1 and MCT4. In a second series, samples from additional 153 HL cases with available clinical data were stained for GLUT1 and LDHA.Results: Membrane bound GLUT1 expression was frequently observed in the tumor cells of HL (49% of all cases) but showed a broad variety between the different Hodgkin lymphoma subtypes: Nodular sclerosing HL subtype displayed a membrane bound GLUT1 expression in the Hodgkin-and Reed-Sternberg cells in 56% of the cases. However, membrane bound GLUT1 expression was more rarely observed in tumor cells of lymphocyte rich classical HL subtype (30%) or nodular lymphocyte predominant HL subtype (15%). Interestingly, in both of these lymphocyte rich HL subtypes as well as in progressively transformed germinal centers, reactive B cells displayed strong expression of GLUT1. LDHA, acting downstream of glycolysis, was also expressed in 44% of all cases. We evaluated the prognostic value of different GLUT1 and LDHA expression patterns; however, no significant differences in progression free or overall survival were found between patients exhibiting different GLUT1 or LDHA expression patterns. There was no correlation between GLUT1 expression in HRS cells and PET standard uptake values.Conclusions: In a large number of cases, HRS cells in classical HL express high levels of GLUT1 and LDHA indicating glycolytic activity in the tumor cells. Although interim-PET is an important prognostic tool, a predictive value of GLUT1 or LDHA staining of the primary diagnostic biopsy could not be demonstrated. However, we observed GLUT1 expression in progressively transformed germinal centers and hyperplastic follicles, explaining false positive results in PET. Therefore, PET findings suggestive of HL relapse should always be confirmed by histology.

Original languageEnglish
Article number586
JournalBMC Cancer
Volume12
DOIs
Publication statusPublished - Dec 10 2012

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Germinal Center
Facilitative Glucose Transport Proteins
Hodgkin Disease
Positron-Emission Tomography
Membranes
Reed-Sternberg Cells
Biopsy
Neoplasms
Neoplasm Staging
Fluorodeoxyglucose F18
Lymphoid Tissue
Glycolysis
lactate dehydrogenase 5
Lactic Acid
Histology
Proteins
B-Lymphocytes

Keywords

  • GLUT1
  • Glycolysis
  • Hodgkin lymphoma
  • Warburg effect

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Hartmann, S., Agostinelli, C., Diener, J., Döring, C., Fanti, S., Zinzani, P. L., ... Hansmann, M. L. (2012). GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers. BMC Cancer, 12, [586]. https://doi.org/10.1186/1471-2407-12-586

GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers. / Hartmann, Sylvia; Agostinelli, Claudio; Diener, Jürgen; Döring, Claudia; Fanti, Stefano; Zinzani, Pier L.; Gallamini, Andrea; Bergmann, Lothar; Pileri, Stefano; Hansmann, Martin Leo.

In: BMC Cancer, Vol. 12, 586, 10.12.2012.

Research output: Contribution to journalArticle

Hartmann, S, Agostinelli, C, Diener, J, Döring, C, Fanti, S, Zinzani, PL, Gallamini, A, Bergmann, L, Pileri, S & Hansmann, ML 2012, 'GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers', BMC Cancer, vol. 12, 586. https://doi.org/10.1186/1471-2407-12-586
Hartmann, Sylvia ; Agostinelli, Claudio ; Diener, Jürgen ; Döring, Claudia ; Fanti, Stefano ; Zinzani, Pier L. ; Gallamini, Andrea ; Bergmann, Lothar ; Pileri, Stefano ; Hansmann, Martin Leo. / GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers. In: BMC Cancer. 2012 ; Vol. 12.
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abstract = "Background: Increased glycolytic activity is a hallmark of cancer, allowing staging and restaging with 18F-fluorodeoxyglucose-positron-emission-tomography (PET). Since interim-PET is an important prognostic tool in Hodgkin lymphoma (HL), the aim of this study was to investigate the expression of proteins involved in the regulation of glucose metabolism in the different HL subtypes and their impact on clinical outcome.Methods: Lymph node biopsies from 54 HL cases and reactive lymphoid tissue were stained for glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and lactate exporter proteins MCT1 and MCT4. In a second series, samples from additional 153 HL cases with available clinical data were stained for GLUT1 and LDHA.Results: Membrane bound GLUT1 expression was frequently observed in the tumor cells of HL (49{\%} of all cases) but showed a broad variety between the different Hodgkin lymphoma subtypes: Nodular sclerosing HL subtype displayed a membrane bound GLUT1 expression in the Hodgkin-and Reed-Sternberg cells in 56{\%} of the cases. However, membrane bound GLUT1 expression was more rarely observed in tumor cells of lymphocyte rich classical HL subtype (30{\%}) or nodular lymphocyte predominant HL subtype (15{\%}). Interestingly, in both of these lymphocyte rich HL subtypes as well as in progressively transformed germinal centers, reactive B cells displayed strong expression of GLUT1. LDHA, acting downstream of glycolysis, was also expressed in 44{\%} of all cases. We evaluated the prognostic value of different GLUT1 and LDHA expression patterns; however, no significant differences in progression free or overall survival were found between patients exhibiting different GLUT1 or LDHA expression patterns. There was no correlation between GLUT1 expression in HRS cells and PET standard uptake values.Conclusions: In a large number of cases, HRS cells in classical HL express high levels of GLUT1 and LDHA indicating glycolytic activity in the tumor cells. Although interim-PET is an important prognostic tool, a predictive value of GLUT1 or LDHA staining of the primary diagnostic biopsy could not be demonstrated. However, we observed GLUT1 expression in progressively transformed germinal centers and hyperplastic follicles, explaining false positive results in PET. Therefore, PET findings suggestive of HL relapse should always be confirmed by histology.",
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AU - Agostinelli, Claudio

AU - Diener, Jürgen

AU - Döring, Claudia

AU - Fanti, Stefano

AU - Zinzani, Pier L.

AU - Gallamini, Andrea

AU - Bergmann, Lothar

AU - Pileri, Stefano

AU - Hansmann, Martin Leo

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N2 - Background: Increased glycolytic activity is a hallmark of cancer, allowing staging and restaging with 18F-fluorodeoxyglucose-positron-emission-tomography (PET). Since interim-PET is an important prognostic tool in Hodgkin lymphoma (HL), the aim of this study was to investigate the expression of proteins involved in the regulation of glucose metabolism in the different HL subtypes and their impact on clinical outcome.Methods: Lymph node biopsies from 54 HL cases and reactive lymphoid tissue were stained for glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and lactate exporter proteins MCT1 and MCT4. In a second series, samples from additional 153 HL cases with available clinical data were stained for GLUT1 and LDHA.Results: Membrane bound GLUT1 expression was frequently observed in the tumor cells of HL (49% of all cases) but showed a broad variety between the different Hodgkin lymphoma subtypes: Nodular sclerosing HL subtype displayed a membrane bound GLUT1 expression in the Hodgkin-and Reed-Sternberg cells in 56% of the cases. However, membrane bound GLUT1 expression was more rarely observed in tumor cells of lymphocyte rich classical HL subtype (30%) or nodular lymphocyte predominant HL subtype (15%). Interestingly, in both of these lymphocyte rich HL subtypes as well as in progressively transformed germinal centers, reactive B cells displayed strong expression of GLUT1. LDHA, acting downstream of glycolysis, was also expressed in 44% of all cases. We evaluated the prognostic value of different GLUT1 and LDHA expression patterns; however, no significant differences in progression free or overall survival were found between patients exhibiting different GLUT1 or LDHA expression patterns. There was no correlation between GLUT1 expression in HRS cells and PET standard uptake values.Conclusions: In a large number of cases, HRS cells in classical HL express high levels of GLUT1 and LDHA indicating glycolytic activity in the tumor cells. Although interim-PET is an important prognostic tool, a predictive value of GLUT1 or LDHA staining of the primary diagnostic biopsy could not be demonstrated. However, we observed GLUT1 expression in progressively transformed germinal centers and hyperplastic follicles, explaining false positive results in PET. Therefore, PET findings suggestive of HL relapse should always be confirmed by histology.

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KW - GLUT1

KW - Glycolysis

KW - Hodgkin lymphoma

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