Cell Membrane ; metabolism ; Gastrointestinal Stromal Tumors ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-kit ; analysis

OBJECTIVETo define the frequency and spectrum of c-kit gene mutations in gastrointestinal stromal tumors (GIST).

METHODSFifty two cases of GIST and 28 cases of other tumors were examined for mutations in exon 11, 9 and 13 of c-kit gene using PCR amplification and DNA sequencing.

RESULTSFourteen out of 25 malignant GIST (56%), while 2 of 27 benign and borderline GIST (7.4%) revealed mutations in exon 11 of c-kit gene (P < 0.01). Most of the mutations consisted of in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, but none of the mutations disrupted the downstream reading frame of the gene. Point mutation and deletion concentrated at 550 - 570 codons but replication clustered within 570 - 585 codons. The mutation pattern in recurrence tissues was the same as the primary ones. Normal tissues adjacent to GIST with or without c-kit gene mutations showed wild type c-kit gene sequence. No mutation was found in exon 9 and 13. Neither c-kit gene expression nor gene mutations was found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 intra-abdomenal fibromitoses and 8 adenocarcinomas.

CONCLUSIONThe mutations in exon 11 of c-kit gene might partially represent one of the molecular mechanisms of GIST. It can be used as a marker for distinguishing benignancy and malignancy of GIST. The mutations did not involve the reading frame. Except for long frame deletion, most mutations also did not affect protein expression. Mutation of c-kit gene in GIST provides a new genotypic marker to distinguish GIST from authentic leiomyomas, leiomyosarcomas, schwannomas and etc.

Base Sequence ; Gastrointestinal Neoplasms ; genetics ; Humans ; Molecular Sequence Data ; Mutation ; Proto-Oncogene Proteins c-kit ; analysis ; genetics ; Proto-Oncogenes

A primary benign schwannoma of the liver is extremely rare. Only nine cases have been reported in the medical literature worldwide and no case has been reported in Korea previously. A 36-yr-old woman was admitted to our hospital with vague epigastric pain. The ultrasound and computed tomography scan revealed a multiseptated cystic mass in the right lobe of the liver. The mass was resected; it was found to be a 5x4x2 cm mass filled with reddish yellow fluid. The histological examination confirmed the diagnosis of a benign schwannoma, proven by positive immunoreaction with the neurogenic marker S-100 protein and a negative response to CD34, CD117 and smooth muscle actin. This is the first report of a benign schwannoma of the liver parenchyma in a Korean patient.
Adult ; Antigens, CD34/analysis ; Female ; Humans ; Liver Neoplasms/diagnosis/*pathology ; Neurilemmoma/diagnosis/*pathology ; Proto-Oncogene Proteins c-kit/analysis

BACKGROUND/AIMS: As the relationship between gastrointestinal stromal tumors (GIST) and interstitial cells of Cajal had become clear, GIST is defined as CD117 positive mesenchymal tumors, and recognized as a new distinct entity among mesenchymal tumors presenting as gastrointestinal submucosal tumors (SMT). To evaluate GISTs in the category of SMTs, we analyzed mesenchymal SMTs immunohistochemically and clinicopathologically. METHODS: Forty-five patients with mesenchymal SMTs, who received surgical or endoscopic resection were retrospectively analyzed for clinical parameters. Immunohistochemical staining for CD117, CD34, NSE, SMA, and S-100 was also performed. RESULTS: Among 45 tumors, 41 (91.1%) expressed CD117 and were diagnosed as GIST. The most frequent location was the gastric body. Except esophageal location (73.3%), GISTs accounted for 100% of SMTs in the gastrointestinal tract. The mixed myoid-neural differentiated type and the spindle cell shape were most common. Metastasis was observed in 5 patients (11%). All of them had tumors larger than 5 cm and died. Their mean survival was 4.6 months. CONCLUSIONS: GIST accounted for majority (91.1%) of SMTs. The presence of metastasis and tumor size at the time of diagnosis indicate poor prognostic factors. Immunohistochemical study is necessary for exact diagnosis of GIST.
Adult ; Aged ; Female ; Gastrointestinal Neoplasms/*chemistry/diagnosis/pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-kit/analysis

Pterygium is a proliferative disease. Recent research has reported that stem cells are involved in the pathogenesis of various proliferative diseases, including solid tumors and diabetic proliferate vitreoretinopathy. In previous literature, we hypothesized that adult stem cells originated from bone marrow were involved in the pathogenesis of pterygium. We proved this by immunohistochemical staining with various stem cell markers. The staining showed adult stem cells in the pterygium. c-kit positive cells were observed primarily in the stroma, and some cells were also found in the basal epithelium. AC133 and CD34 positive cells were primarily found in the basal epithelium and were ovoid shaped, similar to the c-kit cells. However, some cells were found in vascular endothelium. STRO-1 positive cells were found mainly in the stroma and were spindle shaped. In recurrent pterygium, cells were more scattered and the expression pattern was denser. Therefore, we suggest a new theory of pterygium pathogenesis. Inflammation caused by environmental factors triggers the abnormal production of some growth factors and cytokines in order to recover from cellular damage. If these healing signals are excessive, limbal basal cells will be changed to abnormally-altered pterygial cells. The excessive wound healing process and remnant altered cells result in recurrence using the same mechanism.
Stem Cells/*physiology ; Pterygium/*etiology ; Proto-Oncogene Proteins c-kit/analysis ; Peptides/analysis ; Middle Aged ; Humans ; Glycoproteins/analysis ; Bone Marrow Cells/*physiology ; Antigens, CD34/analysis ; Antigens, CD/analysis

We describe an unusual case of extragastrointestinal stromal tumor (EGIST) presenting as a scrotal mass. A 71-year-old man presented with a gradually enlarging scrotal mass with a 20-year duration. Physical examination revealed a huge (as large as volleyball), round, nontender mass occupying the whole scrotum, which was resected completely. Clinical and radiological findings did not comply with any other primary site disease. Under histological examination, the tumor showed a spindle cell pattern with low cellularity, absence of necrotic and mitotic features. immunohistochemical analysis revealed the tumor reactive for CD117 and CD34, while negative for smooth muscle actin, desmin and S-100 protein. To our knowledge, this is the first reported case of an EGIST involving the scrotum.
Aged ; Antigens, CD34 ; analysis ; Gastrointestinal Stromal Tumors ; diagnosis ; Humans ; Immunohistochemistry ; Male ; Proto-Oncogene Proteins c-kit ; analysis ; Scrotum ; pathology ; Sex Cord-Gonadal Stromal Tumors ; chemistry ; pathology

OBJECTIVETo study the clinical significance of interstitial cell of Cajal (ICC) in spontaneous neonatal gastric perforation by examining the expression of c-kit and Cx43 in neonates with this disorder.

METHODSThe gastric specimens of 19 cases of neonatal gastric perforation from 2001 to 2010 and 8 cases of accidental death without digestive tract malformations (control) were collected. Immunohistochemical staining was employed to examine the expression of c-kit and Cx43 (immunomarkers of ICCs) in gastric tissues.

RESULTSThe muscular layer of the stomach wall became thinner or deficient in the gastric perforation group. C-kit and Cx43 positive cells in gastric tissues decreased significantly in the gastric perforation group compared with those in the control group (P＜0.01).

CONCLUSIONSThe development of spontaneous neonatal gastric perforation is associated with the decreased quantity of ICCs and damaged gap junction structure of the stomach wall.

Connexin 43 ; analysis ; Female ; Humans ; Infant, Newborn ; Interstitial Cells of Cajal ; pathology ; Male ; Proto-Oncogene Proteins c-kit ; analysis ; Rupture, Spontaneous ; Stomach ; chemistry ; Stomach Rupture ; congenital ; metabolism ; pathology

Adult ; Appendiceal Neoplasms ; immunology ; pathology ; Dendritic Cell Sarcoma, Follicular ; immunology ; pathology ; Humans ; Immunohistochemistry ; Male ; Proto-Oncogene Proteins c-kit ; analysis ; Receptors, Complement 3b ; analysis

OBJECTIVETo detect the gene mutation of a family with piebaldism.

METHODSDiagnosis of a patient with piebaldism was constructed by pathology, ultrastructural examination and typical clinical-phenotype. Detection of gene mutation was carried out by PCR and DNA sequencing.

RESULTSG 2528A substitution transition in the KIT gene was found in the proband of the family with piebaldism. This mutation resulted in S850N substitution in protein product of KIT gene. No mutation was found in 100 normal individuals and other family members.

CONCLUSIONThe mutation of S850N maybe one cause of clinical phenotype of the family with piebaldism.

Adult ; Base Sequence ; China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mutation, Missense ; Pedigree ; Piebaldism ; genetics ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-kit ; genetics ; Sequence Analysis, DNA

OBJECTIVETo detect gene mutation in proband and his mother from a family with piebaldism.

METHODSDiagnosis of a patient with piebaldism was validated by pathology, ultrastructural examination and the typical clinical manifestation. PCR and DNA sequencing were carried out to detect gene mutation of a family with piebaldism.

RESULTSG1833A transition in the KIT gene was found in the proband of the family with piebaldism. This mutation resulted in V604I substitution in KIT gene. No mutation was found in 100 normal individuals and other family members.

CONCLUSIONThe mutation of V604I is the cause of clinical phenotype of the family with piebaldism.

Base Sequence ; Child ; DNA Mutational Analysis ; Female ; Humans ; Male ; Mutation ; Piebaldism ; genetics ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-kit ; genetics