title: Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung.
abstract: Tumor budding is morphologically defined as infiltration by small clusters of cancer cells. While the biological properties of budding cells in adenocarcinoma (decreased expression of adhesion molecules and of differentiation markers) have been elucidated, those of the cells in squamous cell carcinoma (SqCC) of the lung still remain to be clarified. We examined the clinicopathological data of 217 patients with SqCC of the lung. Furthermore we evaluated the immunohistochemical properties of the budding cells. Tumor budding was observed in 83 (38.2%) patients. A statistically significant difference was observed in overall 5-year survival rates between the cases showing tumor budding and the cases not showing budding (45.6% vs. 64.0%, p<0.001). As compared with cancer cells forming solid nests, budding cells (BCs) exhibited reduced expression levels of the cellular adhesion molecules (E-cadherin; p=0.004, β-catenin; p=0.002) and increased expression levels of laminin-5γ2 (p=0.001). On the other hand, no significant differences in the staining scores for differentiation markers (p63 and podoplanin) were found between BCs and cancer cells forming nests. Multivariate analysis revealed that tumor budding was a significant independent prognostic factor in patients with SqCC of the lung (p=0.022). Tumor budding is an independent adverse prognostic factor in patients with SqCC of the lung. Although budding cells in SqCC exhibited reduced expression levels of the cellular adhesion molecules, the expression levels of specific differentiation markers were retained, suggesting that the budding mechanism in SqCC may differ, at least in part, from that in adenocarcinoma.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Taira
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017978:Receptors, Growth Factor / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D017978:Receptors, Growth Factor