Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin's lymphoma

G. Méhes, Orsolya Matolay, Livia Beke, Marianna Czenke, Ádám Jóna, Zsofia Miltényi, A. Illés, Judit Bedekovics

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Aims: The present study evaluates the impact of hypoxia-related carbonic anhydrase IX and XII isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (cHL). Methods and results: Eighty-one primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analysed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia-related histological and functional data with survival characteristics. Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin–Reed–Sternberg (HRS) cells in 39 of 81 samples (48.1%), while virtually no staining presented in their microenvironment. In contrast, CAXII expression in HRS cells could be demonstrated in only 18 of 77 samples (23.4%), with significant stromal positivity (50 of 77, 64.9%). The CAIX + positive phenotype was strongly associated with lymphocyte depletion (four of four, 100%) and nodular sclerosis (29 of 51, 56.9%) subtypes. CAIX/Ki-67 dual immunohistochemistry demonstrated suppressed cell proliferation in CAIX + positive compared to CAIX negative HRS cells (P < 0.001). Seventy-two months’ progression-free survival (PFS) was significantly lower for the CAIX positive group (0.192) compared with the CAIX negative group (0.771) (P < 0.001), while the overall survival (OS) did not differ (P = 0.097). Conclusion: Hypoxic stress-related adaptation – highlighted by CAIX expression – results in cellular quiescence in HRS cells, potentially contributing to the short-term failure of the standard chemotherapy in cHL.

Original languageEnglish
Pages (from-to)699-708
Number of pages10
JournalHistopathology
Volume74
Issue number5
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

Hodgkin Disease
Cell Proliferation
Lymphocyte Depletion
Sclerosis
Acidosis
Isoenzymes
Disease-Free Survival
Necrosis
Immunohistochemistry
Cell Membrane
Staining and Labeling
Phenotype
Biopsy
Drug Therapy
Carbonic Anhydrase IX
Hypoxia

Keywords

  • adaptation
  • cell cycle
  • Hodgkin's lymphoma
  • hypoxia
  • resistance
  • survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin's lymphoma. / Méhes, G.; Matolay, Orsolya; Beke, Livia; Czenke, Marianna; Jóna, Ádám; Miltényi, Zsofia; Illés, A.; Bedekovics, Judit.

In: Histopathology, Vol. 74, No. 5, 01.04.2019, p. 699-708.

Research output: Contribution to journalArticle

Méhes, G. ; Matolay, Orsolya ; Beke, Livia ; Czenke, Marianna ; Jóna, Ádám ; Miltényi, Zsofia ; Illés, A. ; Bedekovics, Judit. / Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin's lymphoma. In: Histopathology. 2019 ; Vol. 74, No. 5. pp. 699-708.
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abstract = "Aims: The present study evaluates the impact of hypoxia-related carbonic anhydrase IX and XII isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (cHL). Methods and results: Eighty-one primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analysed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia-related histological and functional data with survival characteristics. Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin–Reed–Sternberg (HRS) cells in 39 of 81 samples (48.1{\%}), while virtually no staining presented in their microenvironment. In contrast, CAXII expression in HRS cells could be demonstrated in only 18 of 77 samples (23.4{\%}), with significant stromal positivity (50 of 77, 64.9{\%}). The CAIX + positive phenotype was strongly associated with lymphocyte depletion (four of four, 100{\%}) and nodular sclerosis (29 of 51, 56.9{\%}) subtypes. CAIX/Ki-67 dual immunohistochemistry demonstrated suppressed cell proliferation in CAIX + positive compared to CAIX − negative HRS cells (P < 0.001). Seventy-two months’ progression-free survival (PFS) was significantly lower for the CAIX positive group (0.192) compared with the CAIX negative group (0.771) (P < 0.001), while the overall survival (OS) did not differ (P = 0.097). Conclusion: Hypoxic stress-related adaptation – highlighted by CAIX expression – results in cellular quiescence in HRS cells, potentially contributing to the short-term failure of the standard chemotherapy in cHL.",
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T1 - Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin's lymphoma

AU - Méhes, G.

AU - Matolay, Orsolya

AU - Beke, Livia

AU - Czenke, Marianna

AU - Jóna, Ádám

AU - Miltényi, Zsofia

AU - Illés, A.

AU - Bedekovics, Judit

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Aims: The present study evaluates the impact of hypoxia-related carbonic anhydrase IX and XII isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (cHL). Methods and results: Eighty-one primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analysed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia-related histological and functional data with survival characteristics. Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin–Reed–Sternberg (HRS) cells in 39 of 81 samples (48.1%), while virtually no staining presented in their microenvironment. In contrast, CAXII expression in HRS cells could be demonstrated in only 18 of 77 samples (23.4%), with significant stromal positivity (50 of 77, 64.9%). The CAIX + positive phenotype was strongly associated with lymphocyte depletion (four of four, 100%) and nodular sclerosis (29 of 51, 56.9%) subtypes. CAIX/Ki-67 dual immunohistochemistry demonstrated suppressed cell proliferation in CAIX + positive compared to CAIX − negative HRS cells (P < 0.001). Seventy-two months’ progression-free survival (PFS) was significantly lower for the CAIX positive group (0.192) compared with the CAIX negative group (0.771) (P < 0.001), while the overall survival (OS) did not differ (P = 0.097). Conclusion: Hypoxic stress-related adaptation – highlighted by CAIX expression – results in cellular quiescence in HRS cells, potentially contributing to the short-term failure of the standard chemotherapy in cHL.

AB - Aims: The present study evaluates the impact of hypoxia-related carbonic anhydrase IX and XII isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (cHL). Methods and results: Eighty-one primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analysed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia-related histological and functional data with survival characteristics. Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin–Reed–Sternberg (HRS) cells in 39 of 81 samples (48.1%), while virtually no staining presented in their microenvironment. In contrast, CAXII expression in HRS cells could be demonstrated in only 18 of 77 samples (23.4%), with significant stromal positivity (50 of 77, 64.9%). The CAIX + positive phenotype was strongly associated with lymphocyte depletion (four of four, 100%) and nodular sclerosis (29 of 51, 56.9%) subtypes. CAIX/Ki-67 dual immunohistochemistry demonstrated suppressed cell proliferation in CAIX + positive compared to CAIX − negative HRS cells (P < 0.001). Seventy-two months’ progression-free survival (PFS) was significantly lower for the CAIX positive group (0.192) compared with the CAIX negative group (0.771) (P < 0.001), while the overall survival (OS) did not differ (P = 0.097). Conclusion: Hypoxic stress-related adaptation – highlighted by CAIX expression – results in cellular quiescence in HRS cells, potentially contributing to the short-term failure of the standard chemotherapy in cHL.

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KW - cell cycle

KW - Hodgkin's lymphoma

KW - hypoxia

KW - resistance

KW - survival

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