The Laryngoscope
Lippincott Williams & Wilkins, Inc., Philadelphia
© 2002 The American Laryngological,
Rhinological and Otological Society, Inc.
Immunohistochemical Localization of
Interleukin-10 in Human Oral and
Pharyngeal Carcinomas
Stephen W. Chandler, MD; Christopher H. Rassekh, MD; Susan M. Rodman, EdD;
Barbara S. Ducatman, MD
Objectives/Hypothesis: Interleukin-10 (IL-10) is an
immunosuppressive cytokine with numerous, well-
described effects on the human cellular and humoral
immune response. The oncogenic potential of IL-10 has
been previously investigated in bronchogenic carci-
noma, nasopharyngeal carcinoma, Waldeyer’s ring car-
cinoma, and serum supernatants of patients with squa-
mous cell carcinoma of the head and neck (SCCHN).
The purpose of the study was to determine the preva-
lence and cellular localization of IL-10 in human SC-
CHN. Study Design: Immunohistochemistry of archival
tissues. Methods: Paraffin-embedded archival tissues
were retrospectively obtained from 98 patients with
oral and pharyngeal squamous cell carcinoma. Using a
standard immunohistochemical technique, these speci-
mens were stained with a polyclonal antibody to IL-10.
Results: Using these methods, we found specific local-
ization of antigenic IL-10 to individual tumor cells in
65% of tumors studied. Intensity of staining was signif-
icantly, but inversely, related to tumor grade and N
stage; there also existed a significant staining predispo-
sition for oral cavity lesions when samples from this site
were compared with tissues derived from elsewhere in
the pharynx. Furthermore, IL-10 was not localized to
normal epithelial keratinocytes or inflammatory cells
at the level of sensitivity achieved by the immunohisto-
chemical methods used in the study. Conclusions: The
findings demonstrate that IL-10 can be specifically lo-
calized to human oral and pharyngeal cancer cells.
These data also suggest an inverse association for both
tumor grade and N stage with specific tumor marker
staining. Future studies should investigate the role of
this cytokine in the pathogenesis of human SCCHN. Key
Words: Interleukin-10, cytokine, Waldeyer’s ring, squa-
mous cell cancer, head and neck malignancy, immuno-
histochemistry, oral cavity, oropharynx, nasopharynx.
Laryngoscope, 112:808–815, 2002
INTRODUCTION
Human squamous cell carcinoma of the head and
neck (SCCHN) displays a variable clinical course. Oral
and pharyngeal cancers represent a significant subset
of these malignancies with more than 30,000 new cases
diagnosed per year resulting in nearly 8000 deaths in
the United States.1 Variable tumor behavior may reflect
individual tumor attributes such as the ability to avoid
containment or detection by host immune responses.
Studies indicate that several factors may lead to a rela-
tively immunosuppressed state in patients with SCCHN.2
Such immunosuppression may exert its impact at either
the local (tissue) level or systemically. Soluble factors such
as cytokines may play a role in this phenomenon.
One immunomodulatory agent that has received
attention in oncology research recently is the cytokine
interleukin-10 (IL-10). This molecule was initially iso-
lated by Mosmann et al.3 in 1986 and Fiorentino et al.4
in 1989. Since then, it has been shown to have immu-
nosuppressive bioactivity against several aspects of the
cellular immune system. It was originally identified as
a product of CD4ϩ T-lymphocytes. It is also thought to
be secreted by a number of different cells including
keratinocytes.5
We became interested in such a cytokine after the
discovery that a subset of patients with aggressive na-
sopharyngeal carcinoma had dual infection with
Epstein-Barr virus (EBV) and human papillomavirus
(HPV).6 These “dual” virus cases were associated with
different histological and molecular changes than in the
cases with EBV alone, and some of the HPV subtypes
that were detected were unusual. We postulated that
the EBV might be producing a factor that facilitated
HPV infection. This theory led us to IL-10 because EBV
produces a viral IL-10 with a high degree of homology to
the human IL-10.7 Nasopharyngeal carcinoma speci-
Presented at the Meeting of the Southern Section of the Triological
Society, Marco Island, Florida, January 11, 2001.
Dr. Chandler is the recipient of the Lester Brown Award for Resident
Research.
From the Departments of Otolaryngology—Head and Neck Surgery
(S.W.C., C.H.R., S.M.R.) and Pathology (B.S.D.), West Virginia University,
Morgantown, West Virginia, U.S.A.
Editor’s Note: This Manuscript was accepted for publication December
7, 2001.
Send Correspondence to Christopher H. Rassekh, MD, Post Office Box
9200, Morgantown, WV 26506-9200, U.S.A. E-mail: crassekh@hsc.wvu.edu
Laryngoscope 112: May 2002
808
Chandler et al.: Oral and Pharyngeal Carcinomas