Prognostic significance of micropapillary pattern in lung adenocarcinoma and expression of apoptosis-related markers: caspase-3, bcl-2, and p53.

We evaluated the clinicopathological characteristics and prognostic significance of lung adenocarcinoma with micropapillary pattern (MPP) and analyzed the expression of apoptosis-related markers: caspase-3, bcl-2, and p53. A series of 166 lung adenocarcinoma that had been surgically resected between 2004 and 2009 were reviewed. Histopathologic patterns, presence of tumor necrosis, mitosis, lymphovascular and perineural invasion, the status of pleura, and tumor differentiation were examined. Of the 166 patients; 71 were stage I, 35 stage II, 51 stage III, and nine stage IV. Histologically they were divided into two groups: MPP-positive (n = 55) and MPP-negative (n = 111). The following items were significantly more frequent in the MPP positive group: female gender (p = 0.03), lymph node metastasis (p = 0.031), and pleural invasion (p = 0.045). Age, smoking status, tumor stage, lymphatic invasion, perineural invasion, mitotic count, and survival rates had no statistically significant difference between groups (p > 0.05). In MPP positive tumors, visceral pleural invasion was identified significantly more frequent than in MPP negative tumors, at stage I. Tumors with MPP showed elevated expressions of caspase-3 (94.5%), p53 (60%), and bcl-2 (54.5%). In MPP positive group, the expression of these three markers had no statistically significant impact on survival. In whole population, bcl-2 expression was correlated with a better outcome. We conclude that MPP is associated with poor prognostic factors both in early and late stages in lung adenocarcinoma. Bcl-2 provides prognostic information independent from the MPP.