Quantitative analysis of carbonic anhydrase ix uncovers hypoxia-related functional differences in classical hodgkin lymphoma subtypes

Orsolya Matolay, Lívia Beke, Andrea Gyurkovics, Mónika Francz, Gabriella Varjasi, László Rejtő, Árpád Illés, Judit Bedekovics, Gábor Méhes

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1 Citation (Scopus)

Abstract

Upregulation of carbonic anhydrase IX (CAIX) was found to be associated with unfavorable prognosis and resistance to treatment in a broad spectrum of malignancies, recently also in classical Hodgkin’s lymphoma (cHL). As demonstrated, variable CAIX expression in a significant number of cHL cases was associated with poor treatment response. The current study focused on the quantification CAIX immunopositivity and its relative expression compared to the total CD30+ neoplastic pool using digital image analysis. One hundred and one lymph node samples featuring cHL histology were analyzed for both CD30 and CAIX by immunohistochemistry. Whole histological slides were scanned and immunopositivity was determined as the histoscore (H-score) using the DensitoQuant software module (3DHistech Kft., Budapest, Hungary). CAIX positivity was observed in the HRS-cells of 56/101 cases (55.44%) and frequently observed in the proximity of necrotic foci. CAIX H-scores were highly variable (range: 2.16-90.36, mean 18.7 ± 18.8). Individual CAIX values were independent of the much higher CD30 values (range 3.46-151.3, mean 52.37 ± 30.74). The CAIX/CD30 index proved to be the highest in the aggressive lymphocyte-depleted (LD) subtype (CAIX/CD30: 0.876). The CAIX expression and the CAIX/CD30 relative index can be precisely determined by image analysis, and values reflect the extent of a tumor mass undergoing hypoxic-stress-related adaptation in the most aggressive forms of cHL.

Original languageEnglish
Article number3463
JournalInternational journal of molecular sciences
Volume20
Issue number14
DOIs
Publication statusPublished - Jul 2 2019

Keywords

  • Caix
  • Cd30
  • Classical hodgkin’s lymphoma
  • Digital image analysis
  • Hypoxia
  • Necrosis
  • Virtual slide

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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