Lang Christian, Hrdliczka Emilie, Schweiger Thomas, Glueck Olaf, Lewik Gerrit, Schwarz Stefan, Benazzo Alberto, Lang György, Klepetko Walter, Hoetzenecker Konrad
Department of Thoracic Surgery, Medical University of Vienna, Austria.
J Thorac Dis. 2017 Mar;9(3):621-635. doi: 10.21037/jtd.2017.02.83.
Pulmonary metastasectomy (PM) is a standard procedure in the treatment of stage IV colorectal cancer (CRC). In most centers the indication for PM is solely based on clinical factors without taking the tumor biology into account. This results in diverse outcomes ranging from long-term remission to early recurrence. Inflammation is considered a hallmark of cancer development and progression. On the other hand the accessibility of CRC cells to the immune system reflects the grade of tumor aggressiveness. We sought to investigate the impact of cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2) expression in pulmonary metastases on different outcome parameters following PM.
From 04/2009 to 11/2013 53 patients with complete PM for CRC were included in this single-center study. Tissue samples of resected pulmonary metastases and available corresponding primaries were collected and assessed by immunohistochemistry for COX-2 and PGE2 expression of the tumor tissue and the peritumoral stroma. Results were correlated with clinical outcome parameters.
COX-2 and PGE2 were detected in nearly every pulmonary CRC metastasis. Staining intensities of pulmonary metastases correlated only weakly with intensities found in primary tumors. When dividing metastases in high expressing and low expressing tumors, a trend towards longer recurrence free survival and improved survival was found in tumors with strong COX-2 and PGE2 staining.
In conclusion, this pilot study shows that COX-2 and PGE2 are uniformly overexpressed in pulmonary metastases from CRC. High expression of COX-2 and PGE2 seems to reflect a beneficial tumor biology with late tumor recurrence and prolonged overall survival after PM.
肺转移瘤切除术(PM)是治疗IV期结直肠癌(CRC)的标准手术。在大多数中心,PM的适应症仅基于临床因素,而未考虑肿瘤生物学特性。这导致了从长期缓解到早期复发的不同结果。炎症被认为是癌症发生和发展的标志。另一方面,CRC细胞对免疫系统的易感性反映了肿瘤的侵袭程度。我们试图研究肺转移瘤中环氧合酶-2(COX-2)和前列腺素-E2(PGE2)表达对PM后不同结局参数的影响。
从2009年4月至2013年11月,本单中心研究纳入了53例行完全性PM治疗CRC的患者。收集切除的肺转移瘤组织样本及可用的相应原发肿瘤组织样本,通过免疫组织化学评估肿瘤组织和瘤周基质中COX-2和PGE2的表达。结果与临床结局参数相关。
几乎在每例肺CRC转移瘤中均检测到COX-2和PGE2。肺转移瘤的染色强度与原发肿瘤中的强度仅呈弱相关。将转移瘤分为高表达和低表达肿瘤时,发现COX-2和PGE2染色强的肿瘤有更长无复发生存期和更好生存率的趋势。
总之,这项初步研究表明,COX-2和PGE2在CRC肺转移瘤中均呈一致的过表达。COX-2和PGE2的高表达似乎反映了一种有益的肿瘤生物学特性,即肿瘤复发晚且PM后总生存期延长。