[Double strand break of DNA in gastric adenoma and adenocarcinoma].

BACKGROUND/AIMS: DNA double strand break (DSB) is one of the critical types of DNA damage. When unrepaired DSB is accumulated in the nucleus of the cells having mutations in such genes as p53, it will lead to chromosomal instability and further more to mutation of tumor-activating genes resulting in tumorogenesis. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. The aim of this study was to define the differences in expression of 53BP1 and gamma-H2AX, the markers of DSB, among normal, gastric adenoma, and gastric adenocarcinoma tissues. METHODS: Tissue microarray was made with the tissues taken from 121 patients who underwent gastrectomy for gastric adenocarcinoma, and 51 patients who underwent endoscopic mucosal resection for gastric adenoma. Immunochemical stain was performed for the marker of DSB, 53BP1 and gamma-H2AX in the tissue microarray. The normal tissues were collected from histologically confirmed tissues with no cellular atypia obtained from the patients with gastric adenocarcinoma. RESULTS: In gastric carcinoma cells, 53BP1 and gamma-H2AX were highly expressed as compared to normal epithelial cells and gastric adenoma (p<0.01). There were no differences in the expression of 53BP1 and gamma-H2AX between normal epithelium and gastric adenoma. The expression of 53BP1 in the adenoma with grade II and III atypism was more elevated than in those with grade I atypism. The expression of 53BP1 and gamma-H2AX were not significantly different according to the clinicopathologic parameters in the patients with gastric adenocarcinoma. CONCLUSIONS: The DSB in DNA seems to be associated with the development of gastric adenocarcinoma, but does not affect the premalignant adenoma cells.

Overexpression of protein phosphatase non-receptor type 11 (PTPN11) in gastric carcinomas.

BACKGROUND: Tyrosine phosphorylation and dephosphorylation by protein tyrosine kinases and phosphatases (PTPs), respectively, play crucial roles in cellular signal transduction. Protein phosphatase non-receptor type 11 (PTPN11) is a positive signaling PTP that activates RAS and ERK signaling. Also, the PTPN11 binds with CagA of Helicobacter pylori in gastric epithelial cells. AIM: The aim of this study was to explore whether alteration of PTPN11 protein expression is a feature of gastric cancer cells. METHODS: We analyzed PTPN11 expression in 92 gastric cancer tissues by immunohistochemistry using a tissue microarray method. RESULTS: The gastric cancers expressed PTPN11 in 78 (87%) specimens, while the epithelial cells in normal gastric mucosa did not display any PTPN11 immunoreactivity. The PTPN11 expression in the cancers was associated with the tubular morphology (versus signet ring cell type), the Lauren's intestinal type (versus diffuse type), and the advanced gastric cancer type (versus early gastric cancer type). CONCLUSION: Our data indicate that gastric cancers display a higher expression of PTPN11 protein than the normal cells, suggesting that neo-expression of this positive signaling protein in the cells might play a role in the cancer development. Also, the higher expression of PTPN11 in tubular and intestinal types, where Helicobacter pylori has a definite role in the development of the cancers, suggest a possibility that PTPN11 might play a role in regulation in Helicobacter pylori pathogenesis the gastric cancers.

[A case of non-traumatic hemobilia due to warfarin therapy].

Hemobilia is a hemorrhage into the biliary tract that may follow surgical trauma, liver biopsy, aneurysms, extra- or intra-hepatic tumors of the biliary tract, gallstones, and inflammatory lesion of liver, especially helminthic or pyogenic. Sometimes, it is associated with primary liver cancer. An 84 year-old woman was admitted because of continuous right upper quadrant pain 4 days before admission. Physical examination revealed decreased skin turgor, icteric sclerae and severe tenderness on right upper quadrant abdomen. She had no hepatosplenomegaly, and no rebound tenderness. She has been taking warfarin for 3 weeks before admission because of atrial fibrillation. On admission, serum bilirubin and transaminase were elevated. The level of hemoglobin and hematocrit were 11.3 g/dL and 37.4%, respectively. HBsAg was negative, but IgG anti-HBc and anti-HBs were positive and anti-HCV was negative. Parasite skin test and stool ova count demonstrated non-specific findings. Stool occult blood was strongly positive, and prothrombin time was markedly prolonged. According to endoscopic retrograde cholangiopancreatography, common bile duct was dilated, and filled with blood clot but there was no stone in bile tree. After two weeks, serum transaminase, bilirubin, hemoglobin, hematocrit, and CA19-9 were normalized. We report a case of hemobilia, occurring in a patient with continuous warfarin use.

The first case of intraperitoneal bronchogenic cyst in Korea mimicking a gallbladder tumor.

We present a case of an intraperitoneal bronchogenic cyst located at inferior surface of the liver, next to the gallbladder which clinically mimicked a gallbladder tumor. This is the first case reported in Korea, and we offer reviews of the related literatures. A 48-yr-old woman was admitted to our hospital because of intermittent abdominal pain in right upper quadrant. Computed tomography showed a large mass along-side the gallbladder. During laparotomy, the mass showed an ovoid cystic nature, which was attached to the normal gallbladder and liver bed. Cyst excision with cholecystectomy was performed, and histopathological examination revealed a broncho-genic cyst. Most bronchogenic cysts have a benign nature, but malignant changes have also been reported. Therefore, if a cystic tumor in the abdomen is suspected during preoperative diagnosis, a bronchogenic cyst should be considered in the differential diagnosis.

[The changes of ammonia and epidermal growth factor concentration in gastric juice before and after the Helicobacter pylori eradication].

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is the cause of peptic ulcer diseases, and gastric cancer. Hydrolysis of urea generating ammonia may cause cytotoxic effects on the gastric epithelium. The ammonia may induce the synthesis of epidermal growth factor (EGF) in gastric epithelium as an adaptive cytoprotective mechanism. The first aim was to examine the concentration of ammonia and EGF in gastric juice before and after H. pylori eradication in functional dyspepsia patients. The second aim was to examine the correlation among ammonia concentration, EGF concentration, and inflammatory score of gastritis. METHODS: The concentration of ammonia and EGF were measured by ELISA. The grade and severity of gastritis were measured according to the updated Sydney system. RESULTS: The concentration of ammonia in gastric juice was much higher in the H. pylori positive subjects (10,787 +/- 6,584 micro mol/L) than in the negative subjects (2,339 +/- 1,158 micro mol/L, p<0.0001). The concentrations of EGF in gastric juice was much higher in the positive subjects (1,462 +/- 393 pg/mL) than in the negative subjects (1,088 +/- 499 pg/mL, p<0.005). The concentration of ammonia and EGF in gastric juice showed significant correlation (r=0.63, p<0.0001). The concentrations of ammonia and histologic severities showed significant correlation (r=0.41, p<0.0001). Moreover, the level of EGF in gastric juice and histologic severities showed positive correlation (r=0.20, p<0.005). CONCLUSIONS: As the concentration of ammonia in gastric juices increased, the concentration of EGF was also increased in functional dyspepsia with H. pylori infection. The concentration of EGF in gastric juice may play a role in the adaptive cytoprotection in H. pylori- induced gastritis.

Deep venous thrombosis caused by congenital absence of inferior vena cava, combined with hyperhomocysteinemia.

We present a case of suprarenal and infrarenal absence of the inferior vena cava, combined with hyperhomocysteinemia in a 39-year-old woman who presented with symptoms of deep venous thrombosis. The patient also had a homozygous mutation of C677T methylenetetrahydrofolate reductase. Deep vein thrombosis has a multifactorial etiology involving both genetic and acquired factors. Absence of the inferior vena cava is a rare congenital anomaly, but recently it was confirmed as an important risk factor for the development of deep vein thrombosis, especially in young persons. Hypercoagulability due to hyperhomocysteinemia with a tendency toward venous stasis, mediated by congenital absence of the inferior vena cava is thought to have caused deep vein thrombosis in our patient. To our knowledge, this association has not yet been reported. The clinical features and prognosis of the entity are discussed.

Phakomatosis pigmentovascularis IIb with hypoplasia of the inferior vena cava and the right iliac and femoral veins causing recalcitrant stasis leg ulcers.

We present a patient with phakomatosis pigmentovascularis (PPV) type IIb accompanied with venous hypoplasia, from the inferior vena cava to the superficial femoral vein. Although it is not obvious whether this vascular anomaly, which is probably congenital, is coincidental or not, it is possible that the 2 diseases have some relationship each other, because PPV is thought to result from abnormal vasomotor activity during the embryonic period. In the diagnosis of type II PPV, careful examination and several studies are required to determine systemic involvement that may include large vessel changes.

A Clinical Analysis of PTEN Expressions in Breast Cancers.

PURPOSE: The PTEN gene, a novel tumor suppressor, is localized to chromosome 10q23.3 and shares extensive homology with the cytoskeletal protein, tensin. A high frequency of mutations at the PTEN locus has been described in a variety of neoplasms including breast cancer and Cowden Disease. However, the role of PTEN alterations and its association with clinicopathological factors have not been well established. We investigated the relationship between the PTEN expression and clinicopathological factors. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues from 105 women with breast cancer were evaluated for the PTEN expression and were scored semi-quantitatively based on staining intensity and distribution. RESULTS: were statistically compared with clinicopathological factors. RESULTS: Forty-seven (45%) of the 105 breast cancers had a loss of the PTEN expression. In the recurrent group, 19 of 32 (59%) patients showed a loss of the PTEN expression, whereas in the non-recurrent group, only 28 of 73 (38%) patients showed a loss of the PTEN expression. The loss of PTEN expression correlated with estrogen receptors (ER) (p=0.027), recurrence (p=0.046), HER-2/neu overexpression (p=0.016), disease-free survival (p=0.0163), and overall survival (p=0.0357). In particular, when HER-2/ neu was overexpressed, the overall survival rate correlated with the loss of PTEN expression statistically (p=0.0454), whereas when HER-2/neu was negative, there was no correlation (p=0.9808). Progesterone receptor (PR) and disease stage had no relationship with the PTEN expression. CONCLUSION: Our results support that PTEN plays a role as a tumor suppressor in breast cancer and is a prognostic factor in predicting recurrence.

p53 mutations and microsatellite instabilities in the subtype of intestinal metaplasia of the stomach.

To investigate the potential implication of the subtype of intestinal metaplasia in the progression to the gastric carcinoma, we analyzed the mutations of the p53 gene and microsatellite instability (MSI) both in the complete type (type I) and in the sulphomucin-secreting incomplete type (type III) intestinal metaplasia located adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma. The difference between p53 mutations observed in type I and type III intestinal metaplasia was not statistically significant. No identical mutation of the p53 gene was found in the intestinal metaplasia and carcinoma specimens from the patients. There was no case of intestinal metaplasia showing MSI. In gastric carcinomas, MSI was observed in six cases (40%). The cases harboring BAT-26 instability did not have the mutation of the p53 gene. These data suggest that intestinal metaplasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the genetic alterations as showing in their carcinoma tissues.