1.Microsatellite Instability Is Associated with the Clinicopathologic Features of Gastric Cancer in Sporadic Gastric Cancer Patients.
Shin Hyuk KIM ; Byung Kyu AHN ; Young Su NAM ; Joo Youn PYO ; Young Ha OH ; Kang Hong LEE
Journal of Gastric Cancer 2010;10(4):149-154
PURPOSE: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. MATERIALS AND METHODS: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used. RESULTS: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. CONCLUSIONS: MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.
Colorectal Neoplasms
;
Humans
;
Microsatellite Instability
;
Microsatellite Repeats
;
Stomach Neoplasms
;
Succinimides
2.Qualitative and quantitative evaluation of root injury risk potentially burdening insertion of miniscrew implants.
Joanna ANTOSZEWSKA ; Paulina TRZESNIEWSKA ; Beata KAWALA ; Bjorn LUDWIG ; Hyo Sang PARK
Korean Journal of Orthodontics 2011;41(2):112-120
OBJECTIVE: Microscrew implants (MSIs) offer many advantages, but some complications are known to occur during their insertion. One of the most commonly reported complications is root injury. Our aim was to identify factors associated with root injury and to evaluate their qualitative and quantitative values. METHODS: Thirty-five orthodontists placed MSIs (AbsoAnchor(R), Dentos Co. Ltd, Daegu, Korea) in the upper jaw of typodonts, labially between the second premolar and the first molar, in low and high vertical positions. Root contacts were counted, and distances between MSI apices and roots were measured. Fear level of the orthodontists was surveyed before and after the experiment. Wilcoxon's test, chi-square test, and Mann-Whitney test were used for statistical analysis. RESULTS: Overall root contact rate of MSI insertion was 23.57%. The root contact rate was significantly higher in MSIs inserted at 90degrees (45.71%) than at 30degrees (1.43%). The distance between the dental root and MSI also increased significantly in MSIs inserted at 30degrees. Mean fear level before MSI insertion (4.6) significantly decreased after insertion (3.2); the causative factors were risk of injury to dental root and maxillary sinus or mandibular canal. CONCLUSIONS: Root injury is relatively rare, and oblique angulation reduces the risk of root and MSI contact.
Bicuspid
;
Evaluation Studies as Topic
;
Jaw
;
Maxillary Sinus
;
Molar
;
Succinimides
3.Loss of Heterozygosity on Chromosome 15q15 Near Thrombospondin-1 Gene in Breast Carcinomas.
Jeana KIM ; Kyoung Mee KIM ; Heejeong LEE ; Kyungji LEE ; Mun Gan RHYU ; Anhi LEE ; Seok Jin KANG ; Kyo Young LEE
Korean Journal of Pathology 2009;43(3):221-230
BACKGROUND: Chromosome 15q15 near the thrombospondin-1 (THBS-1) gene may be associated with tumor progression and metastasis. To clarify the potential role of the15q15 region in progression of breast carcinoma, we investigated the loss of heterozygosity (LOH) and the microsatellite instability (MSI) status of chromosome 15q15. Methods : LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. METHODS: LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. RESULTS: Of 77 breast carcinomas containing the heterozygous alleles, 25 (32%) showed LOH in at least one microsatellite marker. Partial LOH and total LOH were detected in 14 (18.27%) and 11 (14.3%) cases. The total LOH were inversely correlated with node metastasis. A single LOH at D15S514 was inversely correlated with nuclear grade and a single LOH at the D15S129 allele was associated with increased expression of the THBS-1 gene. MSI-positive breast carcinomas detected in 14 (17%) cases showed no correlation with any clinicopathologic feature. CONCLUSIONS: These results indicate that loss of the chromosome 15q15 region delays the progression of breast carcinoma because the magnitude of LOH is large and involves the THBS-1 gene and additional genetic elements. The genes located on chromosome 15q15 probably play a tissue-type-dependent role in malignant growth of the tumor.
Alleles
;
Breast
;
Breast Neoplasms
;
Loss of Heterozygosity
;
Microsatellite Instability
;
Microsatellite Repeats
;
Neoplasm Metastasis
;
Succinimides
4.Genetic Instability in Gastric Epithelial Neoplasias Categorized by the Revised Vienna Classification.
Woo Chul CHUNG ; Sung Hoon JUNG ; Kang Moon LEE ; Chang Nyol PAIK ; Jae Wuk KWAK ; Ji Han JUNG ; Jin Young YOO ; Min Kyoung LEE ; In Sik CHUNG
Gut and Liver 2010;4(2):179-185
BACKGROUND/AIMS: The aim of this study was to determine the structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), at multiple tumor suppressor gene loci in gastric epithelial neoplasia categorized by the revised Vienna classification. METHODS: All tissue samples were excised by endoscopic mucosal resection. Sixty category 3 (low-grade adenoma) tissue samples and 51 category 4 samples (high-grade adenoma and intramucosal carcinoma with adenoma) were examined at the 7 sets of microsatellite loci linked to the tumor suppressor gene locus. RESULTS: For category 3 and 4 tissue samples, there were no differences in the frequencies of LOH-positive chromosomes or the extent of chromosomal loss. The Helicobacter-pylori (H. pylori)-positive rate was significantly higher in MSI-positive category 4 samples than in category 3 samples (p=0.04). The frequency of MSI positivity was significantly higher in category 4 samples than in category 3 samples (p=0.003). CONCLUSIONS: H. pylori infection is associated with genetic instability of the premalignant lesion. MSI occurs in the early stages of gastric carcinogenesis and its occurrence increases during malignant transformation. Detection of MSI in premalignant gastric lesions may be a surveillant of risk of malignant transformation.
Adenoma
;
Chromosome Aberrations
;
Genes, Tumor Suppressor
;
Loss of Heterozygosity
;
Microsatellite Instability
;
Microsatellite Repeats
;
Succinimides
5.Regression of Hyperplastic Gastric Polyp after Helicobacter pylori Eradication.
Sang Ah LIM ; Jae Won YUN ; Daewoong YOON ; Wonjae CHOI ; Seung Han KIM ; Jung Wan CHOE ; Mi Na KIM ; Eun Joo KANG ; Jong Jae PARK ; Moon Kyung JOO ; Beom Jae LEE ; Young Tae BAK ; Sang Woo LEE ; Jong Tae PARK
Korean Journal of Gastrointestinal Endoscopy 2011;42(2):74-82
BACKGROUND/AIMS: Recent studies have suggested that the eradication of Helicobacter pylori (Hp) may lead to the regression of hyperplastic polyps (HPPs) in the stomach. We evaluated the sizes of HPPs after Hp eradication and we also compared the clinical parameters between the regression and non-regression groups. METHODS: We enrolled 187 patients who had HPPs in the stomach. The polyps were measured by using biopsy forceps, and the endoscopically observed changes of the polyps were assessed by two endoscopists. RESULTS: Total regression was observed in 68 patients of the eradicated group and in 6 patients in the non-eradicated group (42.5% vs. 22.2%, respectively, p<0.05). The non regression rate was significantly higher for the non-eradicated group than that for the eradicated group (33% vs. 10%, respectively, p<0.05). Comparing between the regression and non-regression groups, the incidence of polyps that were smaller than 10 mm in size and sessile was significantly higher in the regression group. Hp eradication was the only significant predictor of regression. CONCLUSIONS: Hp eradication could be a therapeutic option for Hp positive-hyperplastic gastric polyps, and especially for those that are less than 10 mm in size and sessile.
Biopsy
;
Helicobacter
;
Helicobacter pylori
;
Humans
;
Incidence
;
Polyps
;
Stomach
;
Succinimides
;
Surgical Instruments
6.Clinicopathological Characteristics of Colorectal Cancer according to Microsatellite Instability.
Ki Tae SUK ; Hyun Soo KIM ; Jin Hyung LEE ; Bo Ra KIM ; Moon Young KIM ; Jae Woo KIM ; Soon Koo BAIK ; Sang Ok KWON ; Yosep CHONG ; Mee Yon CHO
Intestinal Research 2009;7(1):14-21
BACKGROUND/AIMS: Microsatellite instability (MSI) is associated with mutations in the DNA mismatch repair system and accounts for 10-15% of all cases of sporadic colorectal cancer (CRC). However, the characteristics and role of MSI as a marker for predicting the prognosis and therapeutic effect on CRC remain unclear. METHODS: Between June 2003 and December 2007, 259 patients (males, 159 [61%]; age, 63 [+/-11] years) who underwent surgery for CRC were retrospectively enrolled. The clinicopathologic characteristics of patients with high-frequency MSI (MSI-H) CRC were reviewed and compared to patients with low-frequency MSI or microsatellite stable CRC. The patient characteristics and MSI-related data were recorded for the following variables: gender, age, clinicopathologic findings, chemotherapy response, recurrence, and survival. RESULTS: MSI-H CRC was diagnosed in 30 patients (12%), low-frequency MSI CRC was diagnosed in 10 patients (4%), and microsatellite stable CRC in was diagnosed in 219 patients (84%). The MSI-H group exhibited the following characteristics: large size, right colon location, positive response to chemotherapy, low recurrence, longer survival, less neural invasion, poor differentiation, diffuse lymphoid reaction, and mucin pool formation. However, in the chemotherapy group (n=180), MSI-H was not a marker of longer survival. Based on Cox-regression analysis, stage IV CRC (OR=6.66; 95% CI, 2.24-53.00), MSI-H (OR=0.17; 95% CI, 0.04-0.73), and a positive response to chemotherapy (OR=0.02; 95% CI, 0.01-0.11) were related to mortality. CONCLUSIONS: MSI-H CRC had less neural invasion and diffuse lymphoid reaction. Further studies regarding the relationship between those pathologic findings and survival are needed.
Colon
;
Colorectal Neoplasms
;
DNA Mismatch Repair
;
Humans
;
Microsatellite Instability
;
Microsatellite Repeats
;
Mucins
;
Prognosis
;
Recurrence
;
Retrospective Studies
;
Succinimides
7.Markers for Screening Lynch Syndrome Are Reliable and Useful for Identifying the Specimen Mislabeling.
Sun Ju BYEON ; Jiwoon CHOI ; Kyung Han NAM ; Bo Gun JANG ; Hee Eun LEE ; Min A KIM ; Woo Ho KIM
Korean Journal of Pathology 2012;46(2):131-136
BACKGROUND: During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs. METHODS: We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123). RESULTS: The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23x10(-4) and the combined power of exclusion was 0.99908. CONCLUSIONS: Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.
Biometric Identification
;
Colonic Neoplasms
;
Colorectal Neoplasms, Hereditary Nonpolyposis
;
Gene Frequency
;
Humans
;
Mass Screening
;
Microsatellite Instability
;
Microsatellite Repeats
;
Pathology, Surgical
;
Succinimides
8.Insulin Resistance in Children and Adolescents Born Small for Gestational Age.
Hye Jeen LEE ; Myung Ki JUNG ; Hong Kyu PARK ; Seung YANG ; Il Tae HWANG ; Hae Ran LEE
Journal of Korean Society of Pediatric Endocrinology 2008;13(1):86-93
PURPOSE: The aim of this study was to determine whether insulin resistance may be present and to analyze factors affecting the development of insulin resistance in children and adolescents born small for gestational age (SGA). METHODS: This study includes 24 children and 18 SGA adolescents and 13 children and 14 control adolescents. All patients underwent a standard, 2-hour oral glucose tolerance test (OGTT). Serum levels of fasting blood sugar, insulin, leptin, adiponectin, homeostasis model assessment-insulin resistance (HOMA- IR), quantitative insulin sensitivity check index (QUICKI), insulin sensitivity index (ISI), mean serum insulin (MSI) and mean serum glucose (MSG) were evaluated. RESULTS: The insulin responses at 30 min and 120 min after glucose load were significantly higher in pubertal SGA than control groups (P<0.05). Impaired glucose tolerance was found from 2 subjects (8.7 %) in prepubertal SGA group and from 3 subjects (15.0%) in pubertal SGA group. None of the patients had developed type 2 diabetes. MSI levels during OGTT were higher in pubertal SGA than in control. Pubertal SGA group had a significantly lower mean serum adiponectin level than control group (9.04+/-4.51 vs. 18.83+/-11.65 microgram/mL, P<0.05). Adiponectin level was correlated with HOMA-IR, QUICKI and ISI (r=-0.37, r=0.32, r=0.51, respectively, P<0.05). CONCLUSION: Adiponectin level was correlated with HOMA-IR, QUICKI and ISI. Pubertal SGA group had a significantly lower mean serum adiponectin level than control group. We suggest the check of insulin resistance using HOMA-IR, QUICKI, ISI and adiponectin is important for the prevention of metabolic syndrome (MS) in adolescents born SGA.
Adiponectin
;
Adolescent
;
Blood Glucose
;
Child
;
Fasting
;
Gestational Age
;
Glucose
;
Glucose Tolerance Test
;
Homeostasis
;
Humans
;
Infant
;
Insulin
;
Insulin Resistance
;
Leptin
;
Succinimides
9.Immunomodulatory effect of canine periodontal ligament stem cells on allogenic and xenogenic peripheral blood mononuclear cells.
Hak Sung KIM ; Kyoung Hwa KIM ; Su Hwan KIM ; Young Sung KIM ; Ki Tae KOO ; Tae Il KIM ; Yang Jo SEOL ; Young KU ; In Chul RHYU ; Chong Pyoung CHUNG ; Yong Moo LEE
Journal of Periodontal & Implant Science 2010;40(6):265-270
PURPOSE: The aim of this study was to investigate the immunomodulatory effects of canine periodontal ligament stem cells on allogenic and xenogenic immune cells in vitro. METHODS: Mixed cell cultures consisting of canine stem cells (periodontal ligament stem cells and bone marrow stem cells) and allogenic canine/xenogenic human peripheral blood mononuclear cells (PBMCs) were established following the addition of phytohemagglutinin. The proliferation of PBMCs was evaluated using the MTS assay. The cell division of PBMCs was analyzed using the CFSE assay. The apoptosis of PBMCs was assessed using the trypan blue uptake method. RESULTS: Periodontal ligament stem cells and bone marrow stem cells inhibited the proliferation of allogenic and xenogenic PBMCs. Both periodontal ligament stem cells and bone marrow stem cells suppressed the cell division of PBMCs despite the existence of a mitogen. No significant differences in the percentages of apoptotic PBMCs were found among the groups. CONCLUSIONS: Canine periodontal ligament stem cells have an immunomodulatory effect on allogenic and xenogenic PBMCs. This effect is not a product of apoptosis of PBMCs but is caused by the inhibition of cell division of PBMCs.
Apoptosis
;
Bone Marrow
;
Cell Culture Techniques
;
Cell Division
;
Diminazene
;
Fluoresceins
;
Humans
;
Immunomodulation
;
Ligaments
;
Periodontal Ligament
;
Stem Cells
;
Succinimides
;
Trypan Blue
10.Microsatellite Instability and p53 Gene Loss of Heterozygosity in Hepatocellular Carcinoma.
Jun Seok KIM ; Man Sup LIM ; Doo Jin KIM ; Joo Seop KIM ; Kwan Seok KIM ; Hong Ki KIM ; Seong Jin CHO ; Mi Jung KWON ; Eun Sook NAM ; Kyung Chan CHOI ; Hyung Sik SHIN ; Gi Bong CHAE
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2009;13(3):143-151
PURPOSE: Hepatocellular carcinoma (HCC) shows various molecular and genetic alterations in its development and progression. Recently, microsatellite instability (MSI) and the loss of heterozygosity (LOH), have been postulated as useful prognostic factors in many malignant tumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSI has been found to be the result of a mismatched DNA pairing. Our objectives were to evaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors. METHODS: MSI analysis was performed by using polymerase chain reaction with 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the 1998 NCI International Workshop) on 50 surgically resected tumors. p53 LOH was detected with 4 markers (D17S796, TP53, D17S5, D17S513). RESULTS: MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCs exhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53 markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequently detected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, p53 LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with higher tumor grade and invasiveness. LOH-High group showed a significant correlation with advanced HCCs and lymphovascular invasion. There was no demonstrated correlation between MSI and p53 LOH was not demonstrated. CONCLUSION: These results suggest that MSI may be involved to some extent in hepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a useful clinical indicator in determining the prognosis among patients with HCC.
Carcinoma, Hepatocellular
;
DNA
;
Genes, p53
;
Genes, Tumor Suppressor
;
Humans
;
Loss of Heterozygosity
;
Microsatellite Instability
;
Microsatellite Repeats
;
Polymerase Chain Reaction
;
Prognosis
;
Succinimides