Schweiger Thomas, Kollmann Dagmar, Nikolowsky Christoph, Traxler Denise, Guenova Emmanuella, Lang György, Birner Peter, Klepetko Walter, Ankersmit Hendrik Jan, Hoetzenecker Konrad
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.
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
Eur J Cardiothorac Surg. 2014 Jul;46(1):92-9. doi: 10.1093/ejcts/ezt542. Epub 2013 Dec 8.
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.
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.
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.
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.
对于有肺转移的特定患者，常规会进行肺转移瘤切除术。根据当前指南，在选择患者进行切除时应考虑肿瘤生物学特性。碳酸酐酶IX（CA9）的表达已被证明是原发性肿瘤生长和转移的一个常见特征，并且它对各种恶性肿瘤的临床结果有负面影响。目前缺乏关于肺转移瘤中CA9的数据。
本研究纳入了44例行根治性肺转移瘤切除术的原发性结直肠癌（CRC）患者。我们通过免疫组织化学法测定了肺转移瘤及相应原发肿瘤中CA9的表达。将表达水平与临床参数及患者吸烟习惯进行关联分析。此外，在HT29细胞中评估了尼古丁处理对STAT3、HIF-1α磷酸化及CA9表达的影响。
切除的肺转移瘤及相应原发肿瘤中CA9的高表达与早期肺转移相关（两者P均<0.001）。此外，CA9表达受患者吸烟习惯的影响。用尼古丁处理HT29细胞在体外可诱导CA9表达。这种诱导与STAT3磷酸化相关，且独立于HIF-1α。
本研究首次提供了CRC肺转移瘤中CA9表达的证据，并提示CA9可作为一种预后标志物。此外，我们的体外和体内数据表明吸烟与CA9表达之间存在关联。对CA9表达进行免疫组织化学评估可能作为选择患者进行肺转移瘤切除术决策的一个额外工具。
