Association of c-Met Activation with Micropapillary Pattern and Small Cluster Invasion in pT1 Lung Adenocarcinoma.
Kaori Koga, Makoto Hamasaki, Fumiaki Kato, Hiroyuki Hayashi, Akinori Iwasaki, Hiroaki Kataoka, Kazuki Nabeshima. Fukuoka University Hospital and School of Medicine, Japan; Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Background: Lung adenocarcinomas with micropapillary pattern (MPP) are associated with frequent nodal metastasis. However, little is known about the mechanisms that underlie MPP-associated nodal metastasis. We have previously reported that carcinomas with MPP tend to undergo small cluster invasion (SCI) in scars and invade lymphatics in pT1 lung adenocarcinomas [Modern Pathology (2007) 20: 514, Virchows Arch (2009) 454: 61]. SCI was defined as markedly resolved acinar-papillary tumor structures with single or small clusters of carcinoma cells invading stroma within fibrotic foci. In this study, we hypothesized that c-Met activation may be involved in the MPP-SCI sequence, since the c-Met tyrosine-kinase receptor and its ligand hepatocyte growth factor play an important role in tumor cell motility and invasion. We tested this hypothesis by analyzing the c-Met activation status immunohistochemically.
Design: We analyzed 146 cases of pT1 lung adenocarcinomas with reference to the presence of MPP, small cluster invasion (SCI), and lymphatic involvement. Expressions of c-Met protein and phosphorylated c-Met were so far examined immuno- histochemically using monoclonal antibodies (c-28, Santa Cruz; No. 248 (Tyr 1235), IBL) in 53 of the 146 cases.
Results: SCI was significantly more frequent in the MPP-positive group (P<0.0001) and was significantly associated with lymphatic involvement (P<0.0001) and nodal metastasis (P=0.0073). c-Met protein was detected in all cases examined as membranous and cytoplasmic staining. Phospho-c-Met was positive in 51/53 cases (96%), and was expressed at high levels in 36/53 cases (68%). High levels of phospho-c-Met expression was significantly associated with MPP (P=0.0054) and SCI (P=0.0009). Patients of the high phospho-c-Met expression group tended to show shorter overall survival compared with those of the low expression group.
Conclusions: C-met activation may play roles in the sequencial process of MPP-SCI-lymph node metastasis.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 258, Tuesday Afternoon