Oral Cancer (2018) 2:1–5
Loss of ARID1A, a component of the SWI/SNF chromatin remodeling
complex, at the invasion front is related to poor outcomes in oral
squamous cell carcinoma
· Kimika Hano
· Katsuaki Bunai
· Chiemi Saigo
· Yusuke Kito
· Toshiyuki Shibata
Received: 11 October 2017 / Accepted: 10 January 2018 / Published online: 19 January 2018
© Springer International Publishing AG, part of Springer Nature 2018
Purpose This study aimed to investigate the relationship between loss of AT-rich interactive domain-containing protein 1A
(ARID1A) expression and the prognosis of patients with oral squamous cell carcinoma (OSCC).
Methods Seventy-ﬁve OSCC tissue specimens were immunohistochemically stained with a speciﬁc antibody to ARID1A.
The immunoreactivity of ARID1A was then correlated with clinicopathological factors, including the prognosis of the
Results Non-tumorous oral squamous cells exhibited nuclear ARID1A staining, whereas the invasive OSCC cells showed
diﬀerent degrees of loss of ARID1A immunoreactivity. Little-to-no ARID1A immunoreactivity was found at the cancer inva-
sion front in 20 of the 75 OSCC tissue specimens, with signiﬁcant association with unfavorable patient outcomes. Notably,
downregulation of ARID1A immunoreactivity was also related to lymphovascular involvement and poor outcome in patients
with T1 and T2 OSCC without lymph node metastasis.
Conclusions The results suggest that loss of ARID1A expression at the cancer invasion front might be related to tumor
progression in many OSCCs.
Keywords Oral squamous cell carcinoma · ARID1A · Chromatin remodeling complex · Outcome
The incidence of oral squamous cell carcinoma (OSCC)
has increased in recent years , and despite progresses in
chemotherapy and radiotherapy, the prognosis of advanced
OSCC is still poor. To develop new targeted molecular
therapies, it is important to unravel the molecular pathways
of OSCC progression.
AT-rich interactive domain-containing protein 1A
(ARID1A; also known as BAF250a, p270, B120, and
SMARCF1) is a subunit of the switch/sucrose non-ferment-
able (SWI/SNF) chromatin remodeling complex, which pos-
sesses DNA-binding activity [2, 3]. Because mutation of the
ARID1A gene is frequently found in many malignant tumors
[4–8], it is now accepted that impaired ARID1A function
is related to the carcinogenesis of various malignancies.
However, the mechanisms by which insuﬃcient ARID1A
expression is linked to carcinogenesis instead of cancer cell
death remain largely unknown.
The prognostic value of impaired ARID1A expression
also remains debatable for many cancers. A meta-scale anal-
ysis did not indicate any prognostic value of ARID1A gene
mutation in head and neck squamous cell carcinoma . In
contrast, a previous tissue microarray study of OSCC, most
of which were at Stage IV (43 of 60 cases), reported that
a low level of ARID1A was related to poor prognosis .
Electronic supplementary material The online version of this
article (http s://doi.org/10.1007 /s415 48-018-0003 -2) contains
supplementary material, which is available to authorized users.
* Tamotsu Takeuchi
Department of Oral and Maxillofacial Surgery, Gifu
University Graduate School of Medicine, Yanagido,
Gifu 501-1193, Japan
Department of Pathology and Translational Research,
Gifu University Graduate School of Medicine, Yanagido,
Gifu 501-1193, Japan