Article
Early pulmonary spreading of primary colorectal carcinoma is associated with carbonic anhydrase IX expression and tobacco smoking
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Authors
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T. Schweiger
- Division of Thoracic Surgery, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna
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D. Kollmann
- Department of Pathophysiology, Medical University of Vienna, Vienna
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C. Nikolowsky
- Division of Thoracic Surgery, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna
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D. Traxler
- Division of Thoracic Surgery, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna
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E. Guenova
- Harvard Skin Disease Research Center, Harvard Medical School, Boston
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G. Lang
- Division of Thoracic Surgery, Medical University of Vienna, Vienna
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P. Birner
- Clinical Institute of Pathology, Medical University of Vienna, Vienna
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W. Klepetko
- Division of Thoracic Surgery, Medical University of Vienna, Vienna
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H. J. Ankersmit
- Division of Thoracic Surgery, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna
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K. Hoetzenecker
- Division of Thoracic Surgery, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna
| Published: | October 14, 2013 |
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Outline
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Objective: Pulmonary metastasectomy is nowadays a common practice in thoracic surgery. However, the selection of patients, which will benefit from a surgical resection is still challenging. Carbonic anhydrase IX (CA9), originally described as a marker for tumor hypoxia, has been described as associated with poor clinical outcome in various malignancies. Data on CA9 expression in pulmonary metastases and its potential role as a predictive value are lacking. Tobacco smoking has been associated with rapid pulmonary spread and upstream signaling in the CA9 pathway. It is still unclear how smoking habits affect CA9 expression and metastatic spreading to the lung.
Methods: The impact of nicotine exposure on phosphorylation of STAT3, HIF-1α and CA9 expression was assessed in HT29 cells. Furthermore, forty-four patients, who suffered from primary colorectal carcinoma (CRC) and underwent curative pulmonary metastasectomy, were included in this study. We determined the expression of CA9 in pulmonary metastases and corresponding primaries by immunohistochemistry. The expression level was correlated with clinical parameters and patients’ smoking habits.
Results: Nicotine treated HT29 cells showed an induction of CA9 in vitro. This induction was accompanied with STAT3 phosphorylation and was independent of HIF-1α. In tissue specimens, CA9 expression was evident in 100% from the primary CRC and 90.1% of paired pulmonary metastases. High expression of CA9 in resected pulmonary metastases and corresponding primary tumors correlated with early pulmonary metastasis (p<0.001, each) and established clinical risk factors. CA9 expression was also increased in former smokers.
Conclusion: This study provides first evidence of CA9 expression in pulmonary metastases of CRC and suggests a role of CA9 as a prognostic marker. Moreover, our in vitro and in vivo data indicate an association between tobacco smoking and CA9 expression, which might contribute to the worse prognosis of former smokers with malignant disease.
