Hypoxia-related carbonic anhydrase IX expression is associated with unfavourable response to first-line therapy in classical Hodgkin's lymphoma.
Histopathology
; 74(5): 699-708, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30636023
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Hodgkin
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Anidrase Carbônica IX
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Antígenos de Neoplasias
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Histopathology
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Hungria