Tohoku J. Exp. Med., 2015 March, 235(3)

Decreased Expression of ARID1A Contributes to Infiltrative Growth of Esophageal Squamous Cell Carcinoma

YOHEI OZAWA,1,2 YASUHIRO NAKAMURA,2 FUMIYOSHI FUJISHIMA,3 SAULO J.A. FELIZOLA,2 KENICHIRO TAKEDA,2 HIROSHI OKAMOTO,1 KEN ITO,1,3 HIROTAKA ISHIDA,1,2 TAKURO KONNO,1,3 TAKASHI KAMEI,1 NORIAKI OHUCHI1 and HIRONOBU SASANO2,3

1Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
2Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
3Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan

The clinical outcome for esophageal squamous cell carcinoma (ESCC) patients is often poor because of the invasive nature of this tumor type. AT-rich interactive domain 1A (ARID1A) functions as a tumor suppressor, and its gene mutation has been reported in various human malignancies. ARID1A is a non-catalytic subunit of the SWItch/Sucrose Non Fermentable (SWI/SNF) chromatin-remodeling complex that regulates gene transcription. Decreased expression of ARID1A protein has been reported to decrease the expression of E-cadherin, an adhesion protein. However, the correlation between ARID1A and E-cadherin expression status in ESCC remains largely unknown. To address this issue, we examined the expression of ARID1A and E-cadherin in tumor specimens excised from 83 ESCC patients using immunohistochemical analysis. The intensity of the ARID1A immunoreactivity was significantly lower in tumors with a growth pattern characterized by ill-defined borders than that in tumors with an expansive growth pattern having a well-demarcated border or tumors with an intermediate growth pattern. Thus, decreased ARID1A immunoreactivity correlated with infiltrative growth of ESCC. In contrast, E-cadherin status did not correlate with the infiltrative growth pattern of ESCC. Moreover, ARID1A expression status did not significantly correlate with any of other clinicopathological factors, E-cadherin expression levels, or the clinical outcome of the patients. On the other hand, the patients with tumors expressing low levels of E-cadherin exhibited significantly lower survival rates than those with high expression. In conclusion, reduced ARID1A expression in tumor tissues contributes to infiltrative growth of ESCC, irrespective of E-cadherin expression levels.

keywords —— AT-rich interactive domain 1A; E-cadherin; epithelial-mesenchymal transition; esophageal squamous cell carcinoma; infiltrative growth pattern

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Tohoku J. Exp. Med., 2015, 235, 185-191

Correspondence: Yohei Ozawa, Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: ozawa.youhei@opal.plala.or.jp