Lymphangiogenesis in patients undergoing pulmonary metastasectomy from metastatic colorectal carcinoma with negative thoracic lymph node staging

Zielsetzung: Pulmonary metastasectomy is an important surgical approach in various metastatic primary tumors. Besides other clinical prognostic factors in patients with pulmonary metastases (PM) of primary colorectal cancer (CRC), positive intrathoracic lymph nodes are thought to be associated with worse clinical outcome in these patients. Therefore, enhanced lymphangiogenesis might pose a crucial step in the disease progression of these patients, even without clinically verified lymph node metastases. We aimed to describe lymphangiogenesis by immunohistochemistry in lymph node negative patients undergoing pulmonary metastasectomy.

Methode: A positive vote of the institutional review board was obtained (Ek1035/2014). Appropriate tissue specimen of 51 pulmonary metastases and 29 corresponding primary tumors were assessed by immunohistochemical staining for podoplanin. Lymphatic microvessel density (LMVD) and lymph-invasion (LI) was determined and correlated with clinicopathological findings.

Ergebnis: Mean LMVD was 12.7 and 13.3 in the PM and primary CRC, respectively. LI was evident in 18 (35.3%) and 17 (58.6%) of PM and corresponding primary tumors, respectively. Samples with evidence of LI had a significantly higher LMVD (p < 0.001). Moreover, LMVD and LI of the primary tumor did not correlate with the corresponding PM. Neither LMVD, nor LI was associated with decreased time to pulmonary recurrence in our study cohort.

Schlussfolgerungen: Herein we could describe that increased lymphangiogenesis and invasion are already present in patients with PM and negative intra-thoracic lymph node staging. Excessive lymphangiogenesis was a prerequisite for histologically evident invasion into the lymphatic system. Interestingly, PMs as hematogenous metastases, displayed another lymphatic phenotype as the corresponding primary CRC.