Am J Clin Pathol 2005;123:376-381
© American Society for Clinical Pathology
Anatomic Pathology / HARD KERATIN–EXPRESSING TUMORS
Expression of Hard α α-Keratins in Pilomatrixoma,
Craniopharyngioma, and Calcifying Odontogenic Cyst
Kaoru Kusama, DDS, PhD,1Yoichi Katayama, MD, PhD,2Keiko Oba, DDS,1Toshiyuki Ishige, DDS,1
Yumiko Kebusa, DDS, PhD,1Jiro Okazawa, DDS, PhD,1Takao Fukushima, MD, PhD,2
and Atsuo Yoshino, MD, PhD2
Key Words: Hard α-keratin; Shadow cell; Ghost cell; Pilomatrixoma; Craniopharyngioma; Calcifying odontogenic cyst;
A b s t r a c t
To examine the properties of shadow and ghost
cells, 3 kinds of antibodies were raised against human
hair proteins and their immunoreactivity was examined
in tumors expressing those cells: pilomatrixoma, 14
cases; craniopharyngioma, 17 cases; and calcifying
odontogenic cyst (COC), 14 cases. Sodium dodecyl
sulfate–polyacrylamide gel electrophoresis and Western
blot analyses demonstrated that 2 polyclonal
antibodies, PA-HP1 and PA-HP 2, reacted strongly with
type I acidic and type II neutral/basic hard α-keratins.
The other monoclonal antibody, MA-HP1, reacted with
type II neutral/basic hard α-keratins. Immunohisto-
chemical examination revealed that all 3 antibodies
reacted only with the hair shaft in sections of normal
skin and dermoid cyst. In all pilomatrixoma cases, 3
antibodies reacted with the cytoplasm of transitional
and shadow cells but not with that of basophilic cells.
Positive reactions were found only in shadow cells of all
13 adamantinomatous craniopharyngiomas. In all
COCs, the antibodies reacted only with ghost cells, not
with other epithelial components. Immunoreactivity for
phosphothreonine, detected in hard α-keratins, also
was found in transitional, shadow, and ghost cells. The
appearance of shadow or ghost cells might represent
differentiation into hair in these 3 kinds of tumors.
In pilomatrixoma, a common benign tumor with hair
matrix cell differentiation, tumor nests are composed of
basophilic, transitional, and shadow cells, corresponding to the
epithelial components of mature hair follicles.1The appearance
of shadow cells in the tumor might represent the endpoint of
hard keratinization of matrix cells into hair cortex.1,2
There are 2 other tumors displaying shadow cells or their
analogue, ghost cells: craniopharyngioma of the pituitary
gland3,4and calcifying odontogenic cyst (COC) of the jaw.5
Recent studies have documented the similarity of the accumu-
lation and alteration of β-catenin in these 3 types of tumors,
suggesting an important role of activation of the Wnt-β-
catenin-TCF-Lef (T-cell factor/lymphoid enhancer factor)
pathway in the pathogenesis of these tumors.6-10It has been
reported that this activated pathway induces differentiation to
hair shafts.8-14Cribier et al2demonstrated the expression of
messenger RNA for human hair keratin basic 1 in transitional
cells by in situ hybridization and suggested that the expression
of hard keratins in transitional cells might resemble the matu-
ration process of the hair shaft. Tateyama et al15demonstrated
immunohistochemically the expression of human hard α-ker-
atins in shadow cells of adamantinomatous craniopharyn-
gioma and proposed that this tumor might show hair follicle
differentiation. Although there have been no English-language
articles on the expression of hard α-keratins in ghost cells,
melanin pigmentation as seen in cortex cells of the normal hair
shaft occasionally is observed in some COC cases.16,17These
findings suggest that differentiation into hair occurs in COC.
To examine the properties of shadow and ghost cells in
pilomatrixoma, craniopharyngioma, and COC, 2 polyclonal
antibodies and 1 monoclonal antibody were raised against
human hair proteins, and their immunoreactivity was tested on
Am J Clin Pathol 2005;123:376-381 381
© American Society for Clinical Pathology
Anatomic Pathology / ORIGINAL ARTICLE
antibodies, the positive reaction for phosphothreonine,
detected in hard α-keratins,18also was found in transitional,
shadow, and ghost cells in the tumors. These findings suggest
that the appearance of shadow or ghost cells might represent
differentiation into hair in the 3 types of tumors.
From the Departments of 1Oral Pathology, Meikai University
School of Dentistry, Saitama, Japan; and 2Neurological Surgery,
Nihon University School of Medicine, Tokyo, Japan.
Address reprint requests to Dr Kusama: Dept of Oral
Pathology, Meikai University School of Dentistry, 1-1, Keyakidai,
Sakado-shi, Saitama, 350-0283, Japan.
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