Molecular Medicine rePorTS 2: 999-1004, 2009
Abstract. The present study investigated multiple extragastroin-
testinal stromal tumors (egiSTs) occurring in the peritoneum,
identified their clinicopathologic and immunohistochemical
features, and examined their c-kiT gene mutations, clonal
status and clonal relationships. Fifteen different tumors of a
multiple egiST from the same female patient were examined
by microscopy and immunohistochemistry, then genomic
dna was isolated from the lesions and, as the control, the
surrounding fibrous connective tissues. PCR amplification
and sequencing were used to investigate the mutation status
of c-kiT gene exons 9, 11, 13 and 17. Finally, a clonality
assay was conducted based on X-chromosome inactivation
mosaicism in female somatic tissues and polymorphisms of
the phosphoglycerate kinase and androgen receptor genes.
immunohistochemical analysis revealed cd117- and cd34-
positive reactivity in the tumors. Mutation analysis identified
the c-kiT gene mutation in exon 13. The clonality assay
revealed a loss of X-chromosome inactivation mosaicism and
an identical inactivated allele in all 15 nodules. no similar
findings were observed in the surrounding fibrous connective
tissues. The c-kiT gene mutation was found in the multiple
egiSTs from the patient. The egiST, like most tumors, was
of monoclonal origin. This and the identical inactivated allele
found in the nodules indicated a common clonal origin for the
gastrointestinal stromal tumors (giSTs) are the most common
mesenchymal tumors of the gastrointestinal tract. it is now
known that their cells of origin are the interstitial cells of cajal.
The commonality of these tumors is immunohistochemical
staining positive for cd117, also known as c-kiT, which is
located at 4q11-12. Several studies have revealed various c-kiT
oncogene mutations, including exon 11 encoding the juxtamem-
brane domain, exon 9 encoding the extra-cellular domain, and
exons 13 and 17 encoding the tyrosine kinase domain (1).
giSTs can occur in the muscularis mucosa and muscularis
propria layers from the esophagus to the rectum, and in extra-
gastrointestinal locations such as the mesentery, omentum
and peritoneum (2-4). Their most common anatomic sites of
origin are the stomach (60-70%), small intestine (20-30%),
colon and rectum (5%), and abdominal cavity (5-7). omentum,
mesentery and retroperitoneal tumors constitute less than 5%
of giSTs (3,8,9).
Malignant giSTs generally metastasize to the omentum
and the mesentery. However, primary tumors may develop in
the omentum, mesentery and peritoneum. extragastrointestinal
stromal tumors (egiSTs) of the peritoneum are rare, and
multiple malignant egiSTs of the peritoneum have not
been reported in recent studies. Moreover, only a few cases
involving the clonality of multiple giSTs have been reported
in the literature (10,11). Here, we describe a case of multiple
and malignant egiSTs in the peritoneum, and elucidate their
immunohistochemical and clinicopathologic characteristics.
The clonality and relationships between these tumors were
additionally investigated to confirm their neoplastic nature.
Materials and methods
Case presentation. a 34-year-old female patient who had
been experiencing periodic abdominal pain for seven days
was admitted to the department of general Surgery, Tangdu
Hospital (Fourth Military Medical university, Xi'an, ShaanXi,
P.r. china). during physical examination, two masses of 10 cm
and 7 cm in diameter were identified in the left upper and left
lower quadrant of the abdomen, respectively. abdominal ultra-
sonography and computed tomography (cT) revealed multiple
round and well-defined soft-tissue masses with homogenous
and heterogeneous patterns in the uterus and spleen, between
the uterus and bladder, in the right lobe of the liver and in the
parietal peritoneum. The cT did not reveal liver metastases
and lymph nodes of pathological size. laboratory tests were
normal, including levels of AFP <10 µg/l, CEA <7.0 µg/l, and
c-KIT gene mutation and clonal origin of multiple
gastrointestinal stromal tumors occurring in the peritoneum
li gong1*, yan-Hong li1,2*, Jun Wang1, Xiao-yan liu1 and Wei ZHang1
departments of 1Pathology, and 2gynaecology and obstetrics, Tangdu Hospital,
Fourth Military Medical university, Xi'an 710038, Shaanxi, P.r. china
received december 22, 2008; accepted July 13, 2009
Correspondence to: Professor Wei Zhang, department of
Pathology, Tangdu Hospital, Fourth Military Medical university,
Xi'an 710038, Shaanxi, P.r. china
Key words: multiple extragastrointestinal stromal tumors, monoclo-
nality, c-kiT gene mutation
gong et al: c-kiT MuTaTion and clonaliTy oF giSTs1004
15. corless cl, Mcgreevey l, Haley a, Town a and Heinrich Mc: kiT
mutations are common in incidental gastrointestinal stromal tumors
one centimeter or less in size. am J Pathol 160: 1567-1572, 2002.
16. Miettinen M, Sobin lH and Sarlomo-rikala M: immunohisto-
chemical spectrum of giSTs at different sites and their differential
diagnosis with a reference to cd117 (kiT). Mod Pathol 13:
17. yamamoto H, oda y, kawaguchi k, nakamura n, Takahira T,
Tamiya S, Saito T, oshiro y, ohta M, yao T and Tsuneyoshi M:
c-kiT and PdgFra mutations in extragastrointestinal stromal
tumor (gastrointestinal stromal tumor of the soft tissue). am J
Surg Pathol 28: 479-488, 2004.
18. Su Q: Precancerous lesions of human hepatocellular carcinoma.
Zhen duan Bing li Xue Za Zhi 10: 112-115, 2003.
19. vogelstein B and Fearon er: use of restriction fragment length
polymorphism to determine the clonal origin of human tumors.
Science 227: 642-644, 1985.
20. allen rc, Zoghbi Hy and Moseley aB: Methylation of Hpaii
and Hhai sites near the polymorphic cag repeat in the human
androgen-receptor gene correlates with X chromosome inactiva-
tion. am J Hum genet 51: 1229-1239, 1992.
21. Su Q, liu Q and Wang SF: clonality analysis technology based on
X chromosome genetic polymorphism and application. Zhonghua
Bing li Xue Za Zhi 31: 162-164, 2002.
22. cai yr, diao Xl, Wang SF, Zhang W, Zhang HT and Su Q:
X-chromosomal inactivation analysis of uterine leiomyomas
reveals a common clonal origin of different tumor nodules in
some multiple leiomyomas. int J oncol 31: 1379-389, 2007.