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

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.

• Authors: Gábor Méhes, Orsolya Matolay, Livia Beke, Marianna Czenke, Ádám Jóna, Zsofia Miltényi, Árpád Illés, Judit Bedekovics
• Journal: Histopathology (Histopathology) Vol. 74 Issue 5 Pg. 699-708 (Apr 2019) ISSN: 1365-2559 [Electronic] England
• PMID: 30636023 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons Ltd.

Chemical References

• Antigens, Neoplasm
• Isoenzymes
• CA9 protein, human
• Carbonic Anhydrase IX

Topics

• Acidosis (enzymology)
• Antigens, Neoplasm (metabolism)
• Biopsy
• Carbonic Anhydrase IX (metabolism)
• Cell Hypoxia
• Cell Proliferation
• Cohort Studies
• Follow-Up Studies
• Hodgkin Disease (drug therapy, enzymology, pathology)
• Humans
• Immunohistochemistry
• Isoenzymes
• Kaplan-Meier Estimate
• Lymph Nodes (diagnostic imaging, enzymology, pathology)
• Necrosis (diagnostic imaging)
• Neoplasm Recurrence, Local (enzymology, pathology)
• Progression-Free Survival