title: Carbonic anhydrase IX is associated with early pulmonary spreading of primary colorectal carcinoma and tobacco smoking.
abstract: OBJECTIVE
  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: 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.
authors: Thomas
authors: T
authors: Schweiger
authors: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors: Dagmar
authors: D
authors: Kollmann
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors: Christoph
authors: C
authors: Nikolowsky
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors: Denise
authors: D
authors: Traxler
authors: Harvard Skin Disease Research Center, Harvard Medical School, Boston, MA, USA.
authors: Emmanuella
authors: E
authors: Guenova
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors: György
authors: G
authors: Lang
authors: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors: Peter
authors: P
authors: Birner
authors: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors: Walter
authors: W
authors: Klepetko
authors: 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.
authors: Hendrik Jan
authors: HJ
authors: Ankersmit
authors: 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.
authors: Konrad
authors: K
authors: Hoetzenecker
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary / Q000601:surgery; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000187:drug effects; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D005731:Ganglionic Stimulants; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009538:Nicotine; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; Cell biology; Colorectal cancer; Pulmonary metastasis