Thomas Schweiger1, Dagmar Kollmann2, Christoph Nikolowsky3, Denise Traxler3, Emmanuella Guenova4, György Lang3, Peter Birner5, Walter Klepetko3, Hendrik Jan Ankersmit6, Konrad Hoetzenecker1. 1. Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria. 2. Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. 3. Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. 4. Harvard Skin Disease Research Center, Harvard Medical School, Boston, MA, USA. 5. Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria. 6. Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria hendrik.ankersmit@meduniwien.ac.at.
Abstract
OBJECTIVES: Pulmonary metastasectomy is performed routinely in selected patients with metastatic spreading to the lungs. According to current guidelines, the tumour biology should be taken into account when selecting patients for a resection. Carbonic anhydrase IX (CA9) expression has been shown to be a common feature in primary tumour growth and metastasis and it negatively affects the clinical outcome in various malignancies. Data on CA9 in pulmonary metastases are lacking. METHODS: Forty-four patients with primary colorectal cancer (CRC) who 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. Furthermore, the impact of nicotine treatment on phosphorylation of STAT3, HIF-1α and CA9 expression was assessed in HT29 cells. RESULTS: High expression of CA9 in resected pulmonary metastases and corresponding primary tumours correlated with early spreading to the lung (both P < 0.001). Moreover, CA9 expression was affected by the smoking habits of the patients. Treating HT29 cells with nicotine resulted in an induction of CA9 in vitro. This induction was associated with STAT3 phosphorylation and was independent of HIF-1α. CONCLUSIONS: 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. Immunohistochemical assessment of CA9 expression might serve as an additional tool in decision-making for selecting patients for pulmonary metastasectomy.
OBJECTIVES: Pulmonary metastasectomy is performed routinely in selected patients with metastatic spreading to the lungs. According to current guidelines, the tumour biology should be taken into account when selecting patients for a resection. Carbonic anhydrase IX (CA9) expression has been shown to be a common feature in primary tumour growth and metastasis and it negatively affects the clinical outcome in various malignancies. Data on CA9 in pulmonary metastases are lacking. METHODS: Forty-four patients with primary colorectal cancer (CRC) who 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. Furthermore, the impact of nicotine treatment on phosphorylation of STAT3, HIF-1α and CA9 expression was assessed in HT29 cells. RESULTS: High expression of CA9 in resected pulmonary metastases and corresponding primary tumours correlated with early spreading to the lung (both P < 0.001). Moreover, CA9 expression was affected by the smoking habits of the patients. Treating HT29 cells with nicotine resulted in an induction of CA9 in vitro. This induction was associated with STAT3 phosphorylation and was independent of HIF-1α. CONCLUSIONS: 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. Immunohistochemical assessment of CA9 expression might serve as an additional tool in decision-making for selecting patients for pulmonary metastasectomy.
Authors: Christian Lang; Emilie Hrdliczka; Thomas Schweiger; Olaf Glueck; Gerrit Lewik; Stefan Schwarz; Alberto Benazzo; György Lang; Walter Klepetko; Konrad Hoetzenecker Journal: J Thorac Dis Date: 2017-03 Impact factor: 2.895
Authors: Thomas Schweiger; Christoph Nikolowsky; Patrick Starlinger; Denise Traxler; Matthias Zimmermann; Peter Birner; Balazs Hegedüs; Balazs Dome; Michael Bergmann; Michael Mildner; Walter Klepetko; Konrad Hoetzenecker; Hendrik Jan Ankersmit Journal: PLoS One Date: 2015-03-20 Impact factor: 3.240
Authors: Simon J A van Kuijk; Ala Yaromina; Ruud Houben; Raymon Niemans; Philippe Lambin; Ludwig J Dubois Journal: Front Oncol Date: 2016-03-29 Impact factor: 6.244