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Coexpression of hypoxia‐inducible factor‐2α, TWIST2, and SIP1 may correlate with invasion and metastasis of salivary adenoid cystic carcinoma
Author(s) -
Zhou Chenchen,
Liu Jeffrey,
Tang Yaling,
Zhu Guiquan,
Zheng Min,
Jiang Jian,
Yang Jing,
Liang Xinhua
Publication year - 2012
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2011.01114.x
Subject(s) - adenoid cystic carcinoma , metastasis , perineural invasion , medicine , immunohistochemistry , adenoid , pathology , western blot , pathological , cancer research , salivary gland , epithelial–mesenchymal transition , carcinoma , oncology , biology , cancer , gene , biochemistry
J Oral Pathol Med (2012) 41 : 424–431 Background: Adenoid cystic carcinoma (ACC) of salivary gland is characterized by advanced local invasion and distant metastasis. Intratumoral hypoxia was reported to be associated with epithelial–mesenchymal transition (EMT) regulators. The purpose of this study was to evaluate the relationship between hypoxia‐inducible factor (HIF)‐2α, TWIST2, and SIP1 expression and the invasion and metastasis in ACC of salivary gland. Method: In vitro we first detected the expression of HIF‐2α, TWIST2, and SIP1 in two ACC cell lines by Western blot and real‐time RT‐PCR. Then, in vivo , a retrospective investigation of 121 patients with ACC from Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University between 1996 and 2005 was carried out using immunohistochemistry to analyze the association between the expression of these three factors and clinical–pathological factors of patients. Results: The protein and mRNA levels of HIF‐2α, TWIST2, and SIP1 in the high‐metastasis cell line (ACC‐M) were much higher than those of the low‐metastasis cell line (ACC‐2). The positive expression of HIF‐2α, TWIST2, and SIP1 (71.07%, 42.98%, and 38.02%, respectively) was associated with the perineural invasion, the local recurrence, and distant metastasis of patients with ACC ( P < 0.05). The patients with the positive coexpression of the three factors had a lower survival rate than those with the negative expression ( P < 0.05). Conclusion: It is proposed that the elevated expression of HIF‐2α, TWIST2, and SIP1 can contribute to invasion and metastasis of ACC, and there might be some correlation between the hypoxia microenvironment and EMT in ACC.