Expression of mesenchymal markers vimentin and fibronectin: the clinical significance in esophageal squamous cell carcinoma.
BACKGROUND
The importance of mesenchymal characteristics has not been fully elucidated in esophageal cancer.


METHODS
Ten normal and 77 tumor specimens were collected. Microarray analysis was performed to analyze the expression patterns of epithelial markers, mesenchymal markers, epithelial mesenchymal transition (EMT)-related genes and stem cell markers. RT-PCR analysis was conducted to confirm the results of microarray analysis. Immunohistochemical analysis was performed to verify the level of protein expression. Statistical analysis was performed to investigate the correlation between selected genes and clinicopathological factors.


RESULTS
Microarray analysis showed that epithelial markers were significantly down-regulated whereas mesenchymal markers and EMT transcription factors were up-regulated in cancer cells. Two types of gene expression patterns were found in the clustering analysis, type 1 tumors and type 2 tumors. Type 1 tumor clusters did not reveal a fixed gene expression pattern whereas type 2 tumor clusters revealed up-regulation of mesenchymal markers EMT inducers and related genes. Vimentin and fibronectin were selected to distinguish between tumor types 1 and 2. Type 2 tumors showed significantly larger tumor sizes (p < 0.0001), wider ranges of lymph node metastasis (p = 0.0057), and a more severe clinical stage (p < 0.0001) than did type 1 tumors. The prognosis of patients with type 2 tumors was significantly worse than that of patients with type 1 tumors. Univariate and multivariate analyses revealed that classification of type 2 tumors was an independent prognostic factor.


CONCLUSIONS
The analysis of mesenchymal markers in esophageal cancer is useful in distinguishing patients with a poor prognosis.
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan, Ts401225@beppu.kyushu-u.ac.jp.
Tomoya
T
Sudo
Takeshi
T
Iwaya
Naohiro
N
Nishida
Genta
G
Sawada
Yusuke
Y
Takahashi
Masahisa
M
Ishibashi
Kohei
K
Shibata
Hiromasa
H
Fujita
Kazuo
K
Shirouzu
Masaki
M
Mori
Koshi
K
Mimori
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C067625:FN1 protein, human; D005353:Fibronectins; D012333:RNA, Messenger; D014746:Vimentin