Research Article
Hypoxia-Inducible Factor-1 Expression in Indonesian
Laryngeal Squamous Cell Carcinoma Patients
Agus Surono, Priyanto Priyanto, and Sagung Rai Indrasari
Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medicine, Universitas Gadjah Mada,
Yogyakarta, Indonesia
Correspondence should be addressed to Agus Surono; agus srn@yahoo.com
Received 16 August 2016; Revised 6 October 2016; Accepted 16 October 2016
Academic Editor: Michiel W. M. van den Brekel
Copyright © 2016 Agus Surono et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objectives. Tis research aimed to determine the association between hypoxia-inducible factor-1 (HIF-1) expression and
laryngeal squamous cell carcinoma clinical stage. Methods. We retrospectively analyzed parafn-embedded tissue from 47 laryngeal
squamous cell carcinoma (LSCC) patients from 2011 to 2014. HIF-1 expression was analyzed by immunohistochemistry using an
anti-HIF-1 mouse monoclonal antibody. Te association between HIF-1 expression and clinical stage was analyzed using the
chi square test. Results. Te glottis was the predominant site of laryngeal squamous cell carcinoma occurrence, and 43/47 (91.5%)
patients presented at an advanced stage. Of the advanced stage patients, 27/43 stained positive for HIF-1 expression and 16/43
stained negative. Of the early stage patients, 2/4 stained positive for HIF-1 expression and 2/4 stained negative. Statistical analysis
did not demonstrate signifcant association of HIF-1 expression. Conclusion. Tere was no statistically signifcant association
between HIF-1 expression and the clinical stage or histological diferentiation of LSCC.
1. Introduction
Laryngeal cancer is common worldwide; it is the third most
common head and neck malignancy, afer nasopharyngeal
and sinonasal tumors [1]. Every year, approximately 12,760
new cases of laryngeal cancer are diagnosed in the United
States, and estimated 3560 deaths are caused by the disease
[2]. Te most common type of laryngeal cancer is squamous
cell carcinoma (SCC), which can range from carcinoma in
situ to poorly diferentiated carcinoma. Laryngeal cancer is
three times more likely to arise in the glottis than the supra-
glottis; cancer in the subglottis is extremely rare and accounts
for just 2% of all laryngeal cancers [3].
A number of factors are believed to contribute to survival
afer laryngeal cancer diagnosis; the tumor stage, tumor site,
treatment strategy, and patient’s age and comorbidities are all
thought to play a role [4]. Tumor hypoxia is a characteristic of
many solid tumors. Te causes of hypoxia are multifactorial
and include abnormal or chaotic tumor vasculature, impaired
blood perfusion, reduced oxygen consumption, and anemia
[5]. Severe tumor hypoxia ultimately leads to tissue necrosis,
but nonlethal levels of hypoxia can impact tumor cell biol-
ogy. Hypoxia-inducible factor-1 (HIF-1) is a transcription
factor that mediates adaptive responses to hypoxia. HIF-
1 activity is increased as a result of genetic alteration
or intratumoral hypoxia in many human cancers. HIF-1
activates gene transcription to increase oxygen availability;
HIF-1 can stimulate angiogenesis or reprogram cellular
metabolism to adapt to reduced oxygen availability [6]. Te
regulation of HIF-1 subunits forms part of the oxygen
response pathway regulation. In the presence of oxygen,
the HIF-1 subunits are hydroxylated and are consequently
degraded. However, in hypoxic conditions, they are not
hydroxylated; HIF-1 is stabilized and can stimulate gene
expression. HIF-1 regulates several important biological
pathways, including those involved in cellular proliferation,
angiogenesis, cell metabolism, apoptosis, and migration [7].
However, the role of HIF-1 activity in laryngeal cancer is
poorly understood, and very few studies regarding HIF-1
in Indonesian laryngeal cancer patients have been published.
Te aim of this study was to determine HIF-1 expression in
laryngeal SCC (LSCC).
Hindawi Publishing Corporation
Journal of Oncology
Volume 2016, Article ID 3215463, 4 pages
http://dx.doi.org/10.1155/2016/3215463