Relationship of Lymph Node Micrometastasis and Micropapillary Component and Their Joint Influence on Prognosis of Patients With Stage I Lung Adenocarcinoma

This study aimed to investigate the relationship between lymph node micrometastasis and histologic patterns of adenocarcinoma, with a particular focus on their joint effect on prognosis. We retrospectively reviewed 235 patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis on prognosis. Lymph node micrometastasis was observed in 35 patients (15%). Patients with micrometastasis had significantly worse recurrence-free survival (P<0.001) and overall survival (P<0.001) compared with those without micrometastasis. Micropapillary component was confirmed as an independent predictor of increased frequency of micrometastasis (P<0.001). Among 62 patients with adenocarcinoma with a micropapillary component, 23 (37%) had lymph node micrometastasis. Micropapillary-positive/micrometastasis-positive patients had significantly worse survival compared with micropapillary-positive/micrometastasis-negative patients (RFS, P=0.039; OS, P=0.002) and micropapillary-negative patients (recurrence-free survival, P<0.001; overall survival, P<0.001). Moreover, the presence of micrometastasis correlated with a higher risk of locoregional recurrence (P=0.031) rather than distant recurrence (P=0.456) in micropapillary-positive patients. In summary, lymph node micrometastasis was more frequently observed in adenocarcinoma with a micropapillary component. Moreover, lymph node micrometastasis could provide helpful prognostic information in patients with resected stage I lung adenocarcinoma with a micropapillary component; thus, immunohistochemical detection of micrometastatic tumor cells in lymph nodes should be recommended.