Schweiger Thomas, Nikolowsky Christoph, Graeter Thomas, Seebacher Gernot, Laufer Jürgen, Glueck Olaf, Glogner Christoph, Birner Peter, Lang György, Klepetko Walter, Ankersmit Hendrik Jan, Hoetzenecker Konrad
Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
Clin Exp Metastasis. 2016 Feb;33(2):133-41. doi: 10.1007/s10585-015-9763-9. Epub 2015 Oct 23.
Pulmonary metastasectomy (PM) is an accepted treatment modality in colorectal cancer (CRC) patients with pulmonary tumor spread. Positive intrathoracic lymph nodes at the time of PM are associated with a poor prognosis and 5-year survival rates of <20 %. Increased lymphangiogenesis in pulmonary metastases might represent an initial step for a subsequent lymphangiogenic spreading. We aimed to evaluate the presence of lymphangiogenesis in clinically lymph node negative patients undergoing PM and its impact on outcome parameters. 71 patients who underwent PM for CRC metastases were included in this dual-center study. Tissue specimens of pulmonary metastases and available corresponding primary tumors were assessed by immunohistochemistry for lymphatic microvessel density (LMVD) and lymphovascular invasion (LVI). Results were correlated with clinical outcome parameters. LMVD was 13.9 ± 8.1 and 13.3 ± 8.5 microvessels/field (mean ± SD) in metastases and corresponding primary CRC; LVI was evident in 46.5 and 58.6 % of metastases and corresponding primary CRC, respectively. Samples with high LMVD had a higher likelihood of LVI. LVI was associated with early tumor recurrence in intrathoracic lymph nodes and a decreased overall survival (p < 0.001 and p = 0.029). Herein, we present first evidence in a well-defined patient collective that increased lymphangiogenesis is already present in a subtype of pulmonary metastases of patients staged as N0 at the time of PM. This lymphangiogenic phenotype has a strong impact on patients' prognosis. Our findings may have impact on the post-surgical therapeutic management of CRC patients with pulmonary spreading.
肺转移瘤切除术(PM)是结直肠癌(CRC)肺转移患者公认的一种治疗方式。PM时胸内淋巴结阳性与预后不良及5年生存率<20%相关。肺转移灶中淋巴管生成增加可能是随后淋巴管源性播散的起始步骤。我们旨在评估接受PM的临床淋巴结阴性患者中淋巴管生成的存在情况及其对预后参数的影响。本双中心研究纳入了71例行PM治疗CRC转移瘤的患者。通过免疫组织化学评估肺转移瘤组织标本及相应的原发肿瘤组织标本的淋巴管微血管密度(LMVD)和淋巴管侵犯(LVI)。结果与临床预后参数相关。转移瘤及相应原发CRC的LMVD分别为13.9±8.1和13.3±8.5个微血管/视野(均值±标准差);LVI分别在46.5%的转移瘤和58.6%的相应原发CRC中可见。LMVD高的样本LVI可能性更高。LVI与胸内淋巴结早期肿瘤复发及总生存期降低相关(p<0.001和p=0.029)。在此,我们在一个明确界定的患者群体中首次证明,在PM时分期为N0的患者的肺转移瘤亚型中已存在淋巴管生成增加。这种淋巴管生成表型对患者预后有重大影响。我们的发现可能会影响CRC肺转移患者术后的治疗管理。