Prognostic Significance of Expression of the Epithelial-Mesenchymal Transition-Related Factor Brachyury in Intrathoracic Lymphatic Spread of Non-Small Cell Lung Cancer.
Brachyury is a transcriptional regulator that plays important roles in epithelial mesenchymal transition (EMT) during development and has been reported to be essential for mesoderm formation in the early human embryo. We investigated Brachyury protein expression in hilar and mediastinal metastatic lymph nodes of non-small cell lung cancer patients and the prognostic significance of Brachyury expression at metastatic sites.



Expression of Brachyury in 115 surgically resected primary lung cancer and corresponding metastatic lymph node samples was evaluated by immunohistochemical staining. The relationships between Brachyury protein expression and the patient's clinicopathological factors and prognosis were analyzed.



Brachyury expression in metastatic lymph nodes was significantly higher than that in the primary tumor (p = 0.012). Patients with high Brachyury expression in the metastatic lymph nodes had significantly poor prognoses (p = 0.0236) compared with patients with low expression. In addition, patients with larger differences in Brachyury expression between metastatic lymph nodes and the primary tumor had significantly poorer prognoses compared with patients with smaller differences (p = 0.0146). The Brachyury protein expression level in metastatic lymph nodes was significantly associated with the protein expression levels of other EMT-related factors (E-cadherin [inverse association], p = 0.0265; Slug, p = 0.029; and interleukin-8, p = 0.0135).



High expression of Brachyury protein in metastatic carcinoma cells in the intrathoracic lymph nodes was associated with poor prognosis of lung cancer patients. Increased Brachyury expression during the metastatic process may confer further potential for invasion and metastasis of cancer cells.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shinichiro
S
Shimamatsu
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. tatsuro@surg2.med.kyushu-u.ac.jp.
Tatsuro
T
Okamoto
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akira
A
Haro
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hirokazu
H
Kitahara
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mikihiro
M
Kohno
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yosuke
Y
Morodomi
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tetsuzo
T
Tagawa
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shinji
S
Okano
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshinao
Y
Oda
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshihiko
Y
Maehara
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000556:secondary*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008482:Mediastinum; D008875:Middle Aged; D011379:Prognosis; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D015996:Survival Rate; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098908:Brachyury Protein
D015820:Cadherins; D005326:Fetal Proteins; D016209:Interleukin-8; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C000604407:SNAI1 protein, human