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 neutralize intracellular acidosis in classical Hodgkin's lymphoma (cHL).

Methods

81 primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analyzed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia related histological and functional data with survival characteristics.

Results

Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin‐Reed‐Sternberg (HRS) cells in 39/81 samples (48.1%) while virtually no staining presented in their microenvironment. In contrast, CAXII expression in HRS‐cells could be demonstrated in only 18/77 samples (23.4%) with significant stromal positivity (50/77, 64.9%). The CAIX+ phenotype was strongly associated with lymphocyte depletion (4/4, 100%) and nodular sclerosis (29/51, 56.9%) subtypes. CAIX/Ki‐67 dual immunohistochemistry demonstrated suppressed cell proliferation in CAIX+ compared to CAIX‐ HRS‐cells (p<0.001). 72 months progression free survival (PFS) was significantly lower for the CAIX+ group (0.192) compared with the CAIX‐ 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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