Relationship between Tumor Angiogenesis and Micrometastases in The Regional Lymph Nodes of Patient with Stage I Non-Small Cell Lung Cancer

Roh, Mee Sook; Lee, Jae Ik; Choi, Phil Jo

Abstract

PURPOSE: This study was performed to evaluate the relation between nodal micrometastasis and tumor angiogenesis, and to assess potential molecular markers pertaining to the development of nodal micrometastasis.
MATERIALS AND METHODS
Immunohistochemical studies were performed to evaluate the expression patterns of Phosphatase, and its Tensin homolog, deleted from chromosome TEN (PTEN), and the vascular endothelial growth factor (VEGF) and microvessel density (MVD) in 41 stage I non-small cell lung cancer (NSCLC), using anti-PTEN monoclonal, anti-VEGF polyclonal and anti-CD34 monoclonal antibodies, respectively. The occult micrometastasis in 503 dissected regional lymph nodes were also evaluated using anti-cytokeratin (CK) monoclonal antibody.
RESULTS
CK positive cells were identified in 13 (31.7%) of the 41 cases and in 23 (4.6%) of the 503 lymph nodes. There were 19 and 22 cases with positive and negative VEGF expressions, respectively, and 10 (52.7%) and 3 (13.6%) of these, respectively, showed nodal micrometastasis (p<0.05). There were 9 cases with loss of PTEN expression, and 4 of these showed nodal micrometastasis, whereas 9 (21.8%) of 32 positive PTEN expression cases showed nodal micrometastasis (p<0.05). The MVD in the tumors with nodal micrometastasis was 60.4+/-22.6, whereas that in the tumors without nodal micrometastasis was 52.0+/-18.2. The loss of PTEN expression, an increased VEGF expression and a high MVD, within primary tumors, were significantly associated with nodal micrometastasis.
CONCLUSION
The results indicate a possible value in using these biological markers, associated with tumor angiogenesis, for predicting the risk of nodal micrometastasis in NSCLC.