PURPOSE: Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. METHODS: IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. RESULTS: Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20-0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03-0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively). CONCLUSION: Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information.
Breast Neoplasms* ; Breast* ; Chromatin Assembly and Disassembly ; Humans ; Immunohistochemistry ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Phenobarbital ; Prognosis* ; Retrospective Studies ; Survival Rate

A glomus tumor in the mediastinum is very uncommon, and only five cases have been reported in the English literature. We recently encountered a 21-year-old woman with an asymptomatic mediastinal mass that measured 5.3 x 4.0 cm. Surgical excision was performed, and the tumor was finally diagnosed as mediastinal glomus tumor with an uncertain malignant potential. After reviewing this case and previous reports, we analyzed the clinicopathologic features associated with progression of such a tumor.
Female ; Glomus Tumor* ; Humans ; Mediastinum ; Young Adult

PURPOSE: The AT-rich interactive domain 1A (ARID1A) gene encodes BRG1-associated factor 250a, a component of the SWItch/Sucrose NonFermentable chromatin remodeling complex, which is considered a tumor suppressor in many tumors. We aimed to investigate the prognostic significance of ARID1A expression in gastric cancers and explore its relationship with clinicopathologic parameters such as mismatch repair protein expression. MATERIALS AND METHODS: Four tissue microarrays were constructed from 191 resected specimens obtained at Soonchunhyang University Cheonan Hospital from 2006 to 2008. Nuclear expression of ARID1A was semiquantitatively assessed and binarized into retained and lost expression. RESULTS: Loss of ARID1A expression was observed in 62 cases (32.5%). This was associated with more frequent vascular invasion (P=0.019) and location in the upper third of the stomach (P=0.001), and trended toward more poorly differentiated subtypes (P=0.054). ARID1A loss was significantly associated with the mismatch repair-deficient phenotype (P=0.003). ARID1A loss showed a statistically significant correlation with loss of MLH1 (P=0.001) but not MSH2 expression (P=1.000). Kaplan-Meier survival analysis showed no statistically significant difference in overall survival; however, patients with retained ARID1A expression tended to have better overall survival than those with loss of ARID1A expression (P=0.053). In both mismatch repair-deficient and mismatch repair-proficient groups, survival analysis showed no differences related to ARID1A expression status. CONCLUSIONS: Our results demonstrated that loss of ARID1A expression is closely associated with the mismatch repair-deficient phenotype, especially in sporadic microsatellite instability-high gastric cancers.
Chromatin Assembly and Disassembly ; Chungcheongnam-do ; DNA Mismatch Repair* ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Phenotype ; Stomach ; Stomach Neoplasms*

Thymic carcinomas are uncommon malignant tumors, and thymic adenocarcinomas are extremely rare. Here, we describe a case of primary thymic adenocarcinoma in a 59-year-old woman. Histological examination of the tumor revealed tubular morphology with expression of cytokeratin 20 and caudal-type homeobox 2 according to immunohistochemistry, suggesting enteric features. Extensive clinical and radiological studies excluded the possibility of an extrathymic primary tumor. A review of the literature revealed only two global cases of primary tubular adenocarcinomas of the thymus with enteric immunophenotype.
Adenocarcinoma* ; Female ; Genes, Homeobox ; Humans ; Immunohistochemistry ; Keratin-20 ; Middle Aged ; Thymoma ; Thymus Gland*

PURPOSE: Recent studies have revealed recurrent alterations in the cell adhesion gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4 (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which is involved in the control of organ size. Here, we investigated the loss of FAT4 expression and its association with clinicopathological risk factors in gastric cancer. MATERIALS AND METHODS: We assessed the expression of FAT4 by using immunohistochemistry on three tissue microarrays containing samples from 136 gastric cancer cases, radically resected in the Soonchunhyang University Cheonan Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4 was semi-quantitatively scored using the H-score system. An H-score of > or =10 was considered positive for FAT4 expression. RESULTS: Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score <10). Loss of FAT4 expression was associated with an increased rate of perineural invasion (H-score <10 vs. > or =10, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. > or =10, mean survival 62.7+/-7.3 months vs. 79.1+/-3.1 months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival. CONCLUSIONS: Loss of FAT4 expression appears to be associated with invasiveness in gastric cancer.
Cell Adhesion ; Chungcheongnam-do ; Classification ; Cytoplasm ; Disease-Free Survival ; Genes, Tumor Suppressor ; Immunohistochemistry ; Organ Size ; Risk Factors ; Stomach Neoplasms*

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
Humans ; Risk Factors

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
Humans ; Risk Factors

BACKGROUND: The family medicine residency program consists mainly of clinical rotations in other specialties and the family medicine-specific training. We conducted this study to investigate how family medicine residents evaluated their training program that include family-oriented medicine, clinical preventive medicine, behavioral science and research in primary care. METHODS: In 2009, third-year residents of 129 training hospitals in Korea were surveyed to investigate the current state and their expectation of the residency program. The contents of questionnaires included training periods, conferences, procedures, interview techniques, outpatient and inpatient consultations, and written thesis. RESULTS: Total 133 out of 142 residents (93.7%) responded that 3 years of training is ideal or pertinent. Residents responded that the types of conference that they need most are journal review (81%), staff lecture (73.2%), and clinical topic review (73.2%), in that order. Procedures and interview techniques that the residents want to learn most were gastroscopy (72.5%), abdominal ultrasonography (65.2%), and pain management (46.4%). Hospitals where family medicine residents do not see hospitalized patients or patients in the outpatient clinic were 7.9% and 6.5%, respectively, whereas hospitals that maintain continuous family medicine outpatient clinics were only 40.8%. Education in outpatient clinic and articlewriting seminars was done less frequently in the secondary hospitals than in the tertiary hospitals. CONCLUSION: Evaluation and quality improvement of family medicine training program as well as specialty rotations should be considered in order to foster better family physicians. The efforts have to be made to minimize the difference in quality of each family medicine residency program.
Ambulatory Care Facilities ; Behavioral Sciences ; Clinical Medicine ; Congresses as Topic ; Family Practice ; Gastroscopy ; Humans ; Inpatients ; Internship and Residency ; Korea ; Outpatients ; Pain Management ; Physicians, Family ; Preventive Medicine ; Quality Improvement ; Referral and Consultation

BACKGROUND: Hemoglobin A1c (HbA1c) was adopted as a new standard criterion for diagnosing diabetes. We investigated the diagnostic utility of HbA1c by comparing the 2003 American Diabetes Association (ADA) diagnostic criteria of diabetes with HbA1c of 6.5%. Furthermore, the cut-off value for HbA1c was investigated using receiver operating characteristic curves. METHODS: This study included 224 subjects without a history of diabetes that had a fasting plasma glucose level of above 100 mg/dL. The subjects had undergone a 75 g oral glucose tolerance test, and diabetes was defined as according to 2003 ADA criteria. RESULTS: The prevalence of newly diagnosed diabetes was 58.2% by the 2003 ADA criteria, and 47.8% by HbA1c of 6.5%, which underestimated the prevalence of diabetes. Compared with the 2003 ADA criteria, the sensitivity and specificity of HbA1c of 6.5% were 73.5% and 89.1%, respectively. The kappa index of agreement between 2003 ADA and HbA1c criteria was 0.60. The cut-off point of HbA1c for diagnosing diabetes was 6.45% (sensitivity, 73.3%; specificity, 88.2%; area under the curve, 0.85). HbA1c was significantly associated with fasting glucose (r = 0.82, P < 0.01), postprandial glucose (r = 0.78, P < 0.01), and homeostasis model assessment of insulin resistance (r = 0.16, P < 0.05). CONCLUSION: For high risk patients whose fasting glucose was more than 100 mg/dL, HbA1c criterion underestimated the prevalence of newly diagnosed diabetes compared to the 2003 ADA criteria, and showed moderate agreement. The cut-off value for HbA1c was 6.45%, which was similar to the recommended diagnostic criterion of HbA1c by the 2009 ADA.
Fasting ; Glucose ; Glucose Tolerance Test ; Hemoglobin A, Glycosylated ; Hemoglobins ; Homeostasis ; Humans ; Insulin Resistance ; Plasma ; Prevalence ; ROC Curve ; Sensitivity and Specificity

BACKGROUND/AIMS: Recent studies have shown that serum interferon gamma-inducible protein-10 (IP-10) concentration decreased after pegylated interferon and ribavirin therapy, and was associated with a sustained virologic response (SVR). The aim of this study was to investigate the clinical significance of the pretreatment IP-10 level and change in serum IP-10 level between 1 month before and after treatment and its association with various virologic responses in patients having chronic hepatitis C (CHC) with genotype 1 undergoing pegylated interferon and ribavirin therapy. METHODS: Thirty-six patients having CHC with genotype I undergoing pegylated interferon and ribavirin therapy who had available stored sera 1 month before and after treatment were enrolled retrospectively. Serum IP-10 levels were measured by ELISA. Serum HCV RNA was measured by RT-PCR (detection limit<50 IU/mL). RESULTS: The mean age of patients (n=36; 21 men) was 53.5 years, and the mean of pretreatment HCV RNA levels was 5.7 log10 IU/mL. The serum IP-10 level at 1 month after treatment significantly decreased from 432.2 to 306.5 pg/mL (p=0.033). The rate of rapid virologic response (RVR), early virologic response (EVR), end-of-treatment response (ETR), and SVR were 58%, 83%, 74%, and 57%, respectively. No significant difference in pretreatment IP-10 levels was observed between the patients with (RVR, EVR, ETR, and SVR) and without various virologic responses (p>0.05). The change in serum IP-10 between 1 month before and after treatment had no clinical meaning based on various virologic responses (p>0.05). CONCLUSIONS: The level of pretreatment IP-10 and change in IP-10 level between 1 month before and after treatment were not predictive factors of a SVR. Additional large-scale studies to determine the SVR-predicting role of serum IP-10 levels in patients with CHC are needed.
Enzyme-Linked Immunosorbent Assay ; Genotype ; Hepatitis C, Chronic ; Hepatitis, Chronic ; Humans ; Interferons ; Retrospective Studies ; Ribavirin ; RNA