Human Leukocyte Antigen-G (HLA-G) Polymorphism and Expression in Breast Cancer Patients

Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3′ untranslated region (UTR) 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407). Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL) compared to the control group (median 10.1 U/mL, P<0.001). The area under the receiver operating characteristic curve (AU-ROC) values of sHLA-G for differentiating breast cancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.ope

Routine chromosomal microarray analysis is necessary in Korean patients with unexplained developmental delay/mental retardation/autism spectrum disorder

BACKGROUND: All over the world, chromosomal microarray (CMA) is now the first tier diagnostic assay for genetic testing to evaluate developmental delay (DD), mental retardation (MR), and autism spectrum disorder (ASD) with unknown etiology. The average diagnostic yield of the CMA test is known to be about 12.2%, while that of conventional G-banding karyotype is below 3%. This study aimed to assess the usefulness of CMA for the purpose of clinical diagnostic testing in the Korean population. METHODS: We performed CMA and multiplex ligation-dependent probe amplification (MLPA) tests in 96 patients with normal karyotype and unexplained DD, MR, or ASD. The CMA was conducted with CytoScan 750K array (Affymetrix, USA) with an average resolution of 100 kb. RESULTS: Pathogenic copy number variations (CNVs) were detected in 15 patients by CMA and in two patients by MLPA for four known microdeletion syndromes (Prader-Willi/Angelman syndrome, DiGeorge syndrome, Miller-Dieker syndrome and Williams syndrome) designated by National Health Insurance system in Korea. The diagnostic yield was 15.6% and 2.1%, respectively. Thirteen (13.5%) patients (excluding cases with pathogenic CNVs) had variants of uncertain clinical significance. There was one patient with a 17.1-megabase (Mb) region of homozygosity on chromosome 4q. CONCLUSIONS: Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD, MR, and ASD in Korea.ope

유방암 환자에서 사람백혈구항원-G의 다형성과 발현

Dept. of Medicine/박사Human leukocyte antigen-G (HLA-G) is implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate the influence of HLA-G polymorphism and expression on breast cancer. Eighty patients with breast cancer and 80 healthy individuals were included in this study. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples, and soluble HLA-G (sHLA-G) was detected by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in 73 breast cancer lesions was also analyzed by immunohistochemistry staining. The HLA-G 3'' untranslated region (UTR) 14 bp sequence insertion was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P=0.0407). Levels of sHLA-G were higher in the breast cancer group (median sHLA-G=117.2 U/mL) compared to the control group (median sHLA-G=10.1 U/mL, P<0.0001) and also presented a significant difference between the ductal carcinoma in situ and control (P<0.0001). The area under the receiver operating characteristic curve (AU-ROC) value of sHLA-G for distinguishing breast cancer from normal controls was 0.89. A similar AU-ROC value was observed for detecting metastasis from all other groups (0.89, P<0.0001), which was greater than that of the current tumor marker CA15-3 (0.54, P<0.0001). Thus, HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.restrictio

Evaluation of peptide nucleic acid-mediated multiplex real-time PCR kits for rapid detection of carbapenemase genes in gram-negative clinical isolates

The emergence of clinical isolates of carbapenemase-producing microbes confers multidrug-resistance to these bacteria and renders them difficult to treat. This study was performed to evaluate peptide nucleic acid (PNA) probe-based multiplex real-time PCR kits used to detect carbapenemase genes. In total, 324 carbapenemase genes, collected from 318 gram-negative clinical isolates in 36 different hospital laboratories, were assayed to evaluate multiplex real-time PCR kits (PANAGENE; Daejeon, Korea). The nine most prevalent carbapenemase genes (KPC, OXA-48, GES, IMP, VIM, NDM, ISAba1-OXA-51, OXA-23, and OXA-58) were included in this study. The sensitivity and specificity of the multiplex real-time PCR assay to all of the carbapenemase genes were above 99.0%, except for ISAba1-OXA-51. The detection limit of the assay was 100 target copies per 25 μL of reaction volume for all of the nine genetic types of carbapenemases, and the genes were all detected in a single three-hour PCR. The assay also showed considerable efficiency (above 80.0%), stable reproducibility (coefficient of variation, below 5.0%) and a long shelf-life (more than eight months) with no cross reactivity. The developed PNA-mediated multiplex real-time PCR assay was useful for the rapid, accurate and simultaneous identification of nine carbapenemase genes in gram-negative clinical isolates, suggesting its potential to help choose the appropriate antibiotics and aid the control of carbapenemase genes.ope

Differences in clinical chemistry values according to the use of two laxatives for colonoscopy

OBJECTIVES: Polyethylene glycol-electrolyte lavage solutions (PEG-ELSs) and sodium phosphate formulations (NaPs) are two major colon cleansing laxatives used in preparation for endoscopic examinations of the gastrointestinal tract. PEG-ELSs are osmotically balanced preparations, whereas NaPs are hyperosmotic purgatives. This study aimed to evaluate the effects of these two laxatives on routine chemistry tests. DESIGN AND METHODS: We retrospectively reviewed 9366 clinical records of patients who had health checkups with or without colonoscopy from July 2010 to June 2011. We compared the values of 19 clinical chemistry parameters in the NaPs group (n=3239) and the PEG-ELSs group (n=1279) with those of controls (without colonoscopy, n=4848). RESULTS: Compared with controls, the NaPs group had higher mean values of inorganic phosphate, sodium, chloride, creatinine, total protein, AST, and ALT, and lower mean values of calcium and potassium, exceeding acceptable biases. Notably, inorganic phosphate showed the largest % bias (51.14%). In the PEG-ELSs laxative group, higher mean values of inorganic phosphorus, creatinine, uric acid, AST, and total bilirubin and a lower mean value of potassium were observed compared with controls, exceeding acceptable biases. The effects of NaPs on inorganic phosphate, calcium, and electrolyte levels exceeded those of PEG-ELSs. CONCLUSIONS: PEG-ELSs rather than NaPs are recommended as the first choice for bowel preparation, taking safety concerns and the reliability of laboratory values into account. Blood chemistry data from blood samples drawn after the ingestion of laxatives for colonoscopy should be interpreted with caution.ope