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Clinical & Experimental Metastasis

, Volume 33, Issue 2, pp 133–141 | Cite as

Increased lymphangiogenesis in lung metastases from colorectal cancer is associated with early lymph node recurrence and decreased overall survival

  • Thomas Schweiger
  • Christoph Nikolowsky
  • Thomas Graeter
  • Gernot Seebacher
  • Jürgen Laufer
  • Olaf Glueck
  • Christoph Glogner
  • Peter Birner
  • György Lang
  • Walter Klepetko
  • Hendrik Jan Ankersmit
  • Konrad HoetzeneckerEmail author
Research Paper

Abstract

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.

Keywords

Pulmonary metastasectomy Colorectal cancer Podoplanin Lymphangiogenesis Lymphovascular invasion 

Notes

Acknowledgments

The work was supported by Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

10585_2015_9763_MOESM1_ESM.jpg (415 kb)
Supplementary Fig. 1 Schematic description of the total study cohort (n = 71) and studied sub-groups (n = 56/n = 15). Supplementary material 1 (JPEG 415 kb)
10585_2015_9763_MOESM2_ESM.jpg (236 kb)
Supplementary Fig. 2 Pulmonary metastases (A) and corresponding primary CRC. (B) samples with evidence of LVI exhibited significantly higher values of LMVD. Supplementary material 2 (JPEG 236 kb)
10585_2015_9763_MOESM3_ESM.jpg (322 kb)
Supplementary Fig. 3 LMVD (A) and LVI (B) of primary CRC and paired pulmonary metastases dependent on the primary tumor site (colon vs rectum). Supplementary material 3 (JPEG 322 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Thomas Schweiger
    • 1
    • 2
  • Christoph Nikolowsky
    • 1
    • 2
  • Thomas Graeter
    • 3
  • Gernot Seebacher
    • 3
  • Jürgen Laufer
    • 4
  • Olaf Glueck
    • 1
    • 2
  • Christoph Glogner
    • 1
    • 2
  • Peter Birner
    • 5
  • György Lang
    • 1
  • Walter Klepetko
    • 1
  • Hendrik Jan Ankersmit
    • 1
    • 2
  • Konrad Hoetzenecker
    • 1
    Email author
  1. 1.Department of Thoracic SurgeryMedical University of ViennaViennaAustria
  2. 2.Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and RegenerationMedical University of ViennaViennaAustria
  3. 3.Department of Thoracic and Vascular SurgeryKlinik LoewensteinLoewensteinGermany
  4. 4.Institute for PathologySLK-Kliniken HeilbronnHeilbronnGermany
  5. 5.Department of PathologyMedical University of ViennaViennaAustria

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