Increased lymphangiogenesis in lung metastases from colorectal cancer is associated with early lymph node recurrence and decreased overall survival.
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.
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.
Thomas
T
Schweiger
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.
Christoph
C
Nikolowsky
Department of Thoracic and Vascular Surgery, Klinik Loewenstein, Loewenstein, Germany.
Thomas
T
Graeter
Department of Thoracic and Vascular Surgery, Klinik Loewenstein, Loewenstein, Germany.
Gernot
G
Seebacher
Institute for Pathology, SLK-Kliniken Heilbronn, Heilbronn, Germany.
Jürgen
J
Laufer
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.
Olaf
O
Glueck
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.
Christoph
C
Glogner
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Peter
P
Birner
Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
György
G
Lang
Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Walter
W
Klepetko
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.
Hendrik Jan
HJ
Ankersmit
Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. konrad.hoetzenecker@meduniwien.ac.at.
Konrad
K
Hoetzenecker
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies
Colorectal cancer; Lymphangiogenesis; Lymphovascular invasion; Podoplanin; Pulmonary metastasectomy