Lymphatic invasion of micropapillary cancer cells is associated with a poor prognosis of pathological stage IA lung adenocarcinomas

Abstract

The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component.

Prevalent and up‐regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance

“…In the present study, we clearly demonstrated that vimentin expression was very prevalent in MPC and was detected in 95/101 (94.1%) AC‐MPC, in accordance with the results of the recent study of Hirano et al . Furthermore, the expression levels were also markedly up‐regulated in MPC, and the vimentin scores of MPC were significantly higher than those of the well‐ and moderately differentiated CAC, as well as the background non‐MPC of the AC‐MPC.…”

“…first suggested the prognostic significance of MPC in lung cancers, especially the risk of highly frequent metastasis, because 33 of their 35 AC‐MPC developed metastases . Most, if not all, subsequent studies have shown that MPC was an adverse prognostic indicator in lung cancers . In the present study, the OS and DFS of AC‐MPC were also significantly worse than those of CAC.…”

“…However, accumulating data have shown that it is also expressed in epithelial cells under some physiological and pathological situations, such as a requirement for migration and/or the acquisition of invasive properties . Several studies have mentioned vimentin expression in lung cancers, although the incidences much varied in the literatures . In the present study, with staining in >1% cells as the cut‐off point, vimentin was positive in 65.5% (78/119) of CAC.…”

“…In the literature, an adverse influence of MPC on patient survival was shown to be closely associated with severer vascular invasion and more advanced node involvement, implying an increase in the invasiveness of MPC . Kawakami et al .…”

“…We subsequently validated this finding in vivo by immunohistochemistry in 101 AC‐MPC and in 119 control CAC. Similar results were observed for CAC with apparent MPC (defined as MPC comprising more than 5% of the tumor cells) in a recent study of Hirano et al ., although only a relative small number of cases and Stage IA disease were investigated …”