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Carbonic Anhydrase IX Overexpression is Associated with Diminished Prognosis in Esophageal Cancer and Correlates with Her-2 Expression

Annals of Surgical Oncology volume 18, Article number: 3330 (2011) Cite this article

Abstract

Background

Carbonic anhydrase IX (CAIX), a transmembrane glycoprotein, seems to play a key role in the adaption of tumor cells to hypoxia. This study was designed to investigate the clinical role of CAIX and its association with Her-2 in a large cohort of adeno- (AC) and squamous cell carcinomas (SCC) of the esophagus and their metastases.

Methods

Expression of CAIX and Her-2 was investigated immunohistochemically in formalin fixed, paraffin-embedded tissue from 330 esophageal cancers (182 ACS, 148 SCCs). Corresponding lymph node metastases in 137 cases, distant metastases in 34 cases, and local recurrences in 14 cases were analyzed for CAIX expression.

Results

A total of 147 cases (44.5%) showed strong CAIX expression (AC: 46.7%; ACC: 41.9%). CAIX status of the primary tumor influenced CAIX expression in corresponding lymph node metastases (P < 0.001, linear regression). High CAIX-expression was an independent prognostic factor for shorter overall and disease-free survival (P ≤ 0.05, Cox regression). Twenty-nine ACs (15.9%) and 6 SCCs (4.1%) showed Her-2 overexpression. In AC, a significant positive correlation between the Her-2 status and CAIX expression was found (P = 0.009, chi-square test).

Conclusions

High CAIX expression is associated with shorter survival in esophageal cancer, and the hypoxic phenotype seems to be preserved at least during formation of lymph node metastases. Inhibition of CAIX might reduce the ability of tumor cells to establish disseminated disease. In Her-2 overexpressing ACs, blocking of this tyrosine kinase, e.g., by monoclonal antibodies, might induce this effect.

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Author information

Affiliations

  1. Institute of Pathology, Medical University of Vienna, Vienna, Austria

    Peter Birner MD, MSc, Julia Friedrich MD & Fritz Wrba MD

  2. Department of Surgery, University of Vienna, Vienna, Austria

    Bettina Jesch BMS, Martin Riegler MD, Johannes Zacherl MD & Sebastian F. Schoppmann MD

  3. Department of Oncology, Medical University of Vienna, Vienna, Austria

    Michael Hejna MD

  4. Department of Pathology, Kaiserin-Elisabeth Spital, Vienna, Austria

    Andrea Schultheis MD

  5. Department of Surgery, Comprehensive Cancer Center Vienna, University of Vienna, Vienna, Austria

    Sebastian F. Schoppmann MD

Authors
  1. Peter Birner MD, MSc
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  2. Bettina Jesch BMS
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  3. Julia Friedrich MD
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  4. Martin Riegler MD
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  6. Michael Hejna MD
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  7. Fritz Wrba MD
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  9. Sebastian F. Schoppmann MD
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Correspondence to Sebastian F. Schoppmann MD.

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Birner, P., Jesch, B., Friedrich, J. et al. Carbonic Anhydrase IX Overexpression is Associated with Diminished Prognosis in Esophageal Cancer and Correlates with Her-2 Expression. Ann Surg Oncol 18, 3330 (2011). https://doi.org/10.1245/s10434-011-1730-3

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  • DOI: https://doi.org/10.1245/s10434-011-1730-3

Keywords

  • Squamous Cell Carcinoma
  • Esophageal Cancer
  • Correspond Lymph Node
  • CAIX Expression
  • Local Lymph Node Metastasis