Mi Young Kim

Homozygous deletion of CDKN2A (p16, p14) and CDKN2B (p15) genes is a poor prognostic factor in adult but not in childhood B-lineage acute lymphoblastic leukemia: a comparative deletion and hypermethylation study

The biological behavior of childhood B-lineage acute lymphoblastic leukemia (B-ALL) is different from that of adults. We performed a comprehensive analysis of the deletion and the methylation profile of CDKN2A (hereafter identified separately as p16 and p14, for the different proteins encoded) and CDKN2B (hereafter p15) in 91 newly diagnosed B-ALL patients (61 children, 30 adults). The prognostic significance of the profiles of these genes and the association between alterations in these genes and known cytogenetic prognostic factors (BCR/ABL; ETV6/RUNX1, formerly TEL/AML1; MLL rearrangement; and ploidy changes of chromosomes) were also assessed. The prevalence of homozygous deletion, hemizygous deletion, and no deletion of the 9p21 region was 11.5%, 16.4%, and 72.1%, respectively, in children and 30.0%, 20.0%, and 50.0%, respectively, in adults; the higher incidence of homozygous deletion in adults was significant (P=0.029). Homozygous deletion was associated with poor overall survival in adults (P=0.019), but not in children. The incidence of promoter methylation of p16, p14, and p15 was 34.4%, 14.8%, and 34.4%, respectively, in children and 26.7%, 10.0%, and 40.0%, respectively, in adults, with no significant difference between the two groups. No significant association was observed between deletion and methylation or with known cytogenetic prognostic factors. The difference in incidence, distribution, and prognostic effect of homozygous deletion in children and adults may explain the prognostic disparity.

Breast Cancer Detected with Screening US: Reasons for Nondetection at Mammography

PURPOSEnTo retrospectively review the mammograms of women with breast cancers detected at screening ultrasonography (US) to determine the reasons for nondetection at mammography.nnnMATERIALS AND METHODSnThis study received institutional review board approval, and informed consent was waived. Between 2003 and 2011, a retrospective database review revealed 335 US-depicted cancers in 329 women (median age, 47 years; age range, 29-69 years) with Breast Imaging Reporting and Data System breast density type 2-4. Five blinded radiologists independently reviewed the mammograms to determine whether the findings on negative mammograms should be recalled. Three unblinded radiologists re-reviewed the mammograms to determine the reasons for nondetection by using the reference location of the cancer on mammograms obtained after US-guided wire localization or breast magnetic resonance imaging. The number of cancers recalled by the blinded radiologists were compared with the reasons for nondetection determined by the unblinded radiologists.nnnRESULTSnOf the 335 US-depicted cancers, 63 (19%) were recalled by three or more of the five blinded radiologists, and 272 (81%) showed no mammographic findings that required immediate action. In the unblinded repeat review, 263 (78%) cancers were obscured by overlapping dense breast tissue, and nine (3%) were not included at mammography owing to difficult anatomic location or poor positioning. Sixty-three (19%) cancers were considered interpretive errors. Of these, 52 (82%) were seen as subtle findings (46 asymmetries, six calcifications) and 11 (18%) were evident (six focal asymmetries, one distortion, four calcifications).nnnCONCLUSIONnMost breast cancers (81%) detected at screening US were not seen at mammography, even in retrospect. In addition, 19% had subtle or evident findings missed at mammography.

Comparison of the MicroScan, VITEK 2, and Crystal GP with 16S rRNA sequencing and MicroSeq 500 v2.0 analysis for coagulase-negative Staphylococci

BackgroundThree phenotypic identification systems (MicroScan, VITEK 2, and Crystal GP) were evaluated for their accuracy to identify coagulase-negative staphylococci (CNS). A total of 120 clinical isolates confirmed to be CNS via 16S rRNA sequencing and analysis with the MicroSeq 500 v2.0 database were assessed.ResultsThe MicroScan, VITEK 2, and Crystal GP systems correctly identified 82.5%, 87.5%, and 67.5% of the isolates, respectively. Misidentification was the main problem in MicroScan (10.8%) and Crystal GP (23.3%) systems, whereas the main problem of VITEK 2 was low-level discrimination (7.5%).ConclusionNone of the 3 phenotypic systems tested could accurately and reliably identify CNS at the species level. Further verifications such as biochemical testing or 16S rRNA sequencing together with analysis using a comparable database might be helpful in this regard.

18F-FDG uptake in breast cancer correlates with immunohistochemically defined subtypes

AbstractObjectivesTo determine whether a correlation exists between maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the subtypes of breast cancer.MethodsThis retrospective study involved 548 patients (mean age 51.6xa0years, range 21–81xa0years) with 552 index breast cancers (mean size 2.57xa0cm, range 1.0–14.5xa0cm). The correlation between 18F-FDG uptake in PET/CT, expressed as SUVmax, and immunohistochemically defined subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative) was analyzed.ResultsThe mean SUVmax value of the 552 tumours was 6.07u2009±u20094.63 (range 0.9–32.8). The subtypes of the 552 tumours were 334 (60xa0%) luminal A, 66 (12xa0%) luminal B, 60 (11xa0%) HER2 positive and 92 (17xa0%) triple negative, for which the mean SUVmax values were 4.69u2009±u20093.45, 6.51u2009±u20094.18, 7.44u2009±u20094.73 and 9.83u2009±u20096.03, respectively. In a multivariate regression analysis, triple-negative and HER2-positive tumours had 1.67-fold (Pu2009<u20090.001) and 1.27-fold (Pu2009=u20090.009) higher SUVmax values, respectively, than luminal A tumours after adjustment for invasive tumour size, lymph node involvement status and histologic grade.ConclusionFDG uptake was independently associated with subtypes of invasive breast cancer. Triple-negative and HER2-positive breast cancers showed higher SUVmax values than luminal A tumours.Key Points• 18F-FDG PET demonstrates increased tissue glucose metabolism, a hallmark of cancers.n • Immunohistochemically defined subtypes appear significantly associated with FDG uptake (expressed as SUVmax).n • Triple-negative tumours had 1.67-fold higher SUVmaxvalues than luminal A tumours.n • HER2-positive tumours had 1.27-fold higher SUVmaxvalues than luminal A tumours.

Copy number variations associated with idiopathic autism identified by whole-genome microarray-based comparative genomic hybridization.

Objectives Autism spectrum disorder (ASD) has been thought to have strong genetic background, but major contributing genes or associated molecular–genetic pathways are yet to be identified. To explore the idiopathic ASD-associated copy number variations (CNVs), we conducted case–control study using whole-genome copy number analysis. Methods Whole-genome microarray-based comparative genomic hybridization was carried out on 28 children (24 boys and four girls) diagnosed as ASD and 62 Korean adults (45 males and 17 females) without any signs of abnormalities and family history of genetic disorders as normal controls. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism were used for quantitative verification of the ASD-associated CNVs. Results Thirty-eight CNVs were identified. Among them, the distributions of copy number loss CNVs on 8p23.1 (odds ratio: 5.1, 95% confidence interval: 1.7–14.5, P=0.003) and on 17p11.2 (odds ratio: uncalculable because of zero cell, P=0.008) were found to be significantly different between ASD and control groups. DEFENSIN family occurs in a cluster at 8p23.1 region. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism coherently showed reduced copy number of DEFENSIN in cases with 8p23.1 copy number loss CNV, which validated microarray-based comparative genomic hybridization results; but there are no known coding genes in the CNV on 17p11.2. Conclusion Our approach as well as results can help to elucidate the genetic mechanism of idiopathic ASD.

Sonoelastography in Distinguishing Benign from Malignant Complex Breast Mass and Making the Decision to Biopsy

Objective To evaluate the additional effect of sonoelastography on the radiologists ability for distinguishing benign from malignant complex breast masses and to decide whether to perform biopsy by B-mode US. Materials and Methods One hundred eighteen complex breast masses (15 malignant lesions, 103 benign lesions) were included. Five blinded readers independently assessed the likelihood of the malignancy score from 1 to 5 for two data sets (B-mode ultrasound alone and B-mode ultrasound with sonoelastography). Elasticity scores were categorized as 0, 1, or 2 based on the degree and distribution of strain of the echogenic component within complex masses. The readers were asked to downgrade the likelihood of the malignancy score when an elasticity score of 0 was assigned and to upgrade the likelihood of the malignancy score when an elasticity score of 2 was assigned. The likelihood of the malignancy score was maintained as it was for the lesions with an elasticity score of 1. The Az values, sensitivities, and specificities were compared. Results The Az value of B-mode ultrasound with sonoelastography (mean, 0.863) was greater than that of B-mode ultrasound alone (mean, 0.731; p = 0.001-0.007) for all authors. The specificity of B-mode ultrasound with sonoelastography (mean, 37.1%) was greater than that of B-mode ultrasound alone (mean, 3.8%; p < 0.001) for all readers. The addition of sonoelastography led to changes in decisions. A mean of 33.6% of benign masses were recommended for follow-up instead of biopsy. Conclusion For complex breast masses, sonoelastography allows increase in both the accuracy in distinguishing benign from malignant lesions and the specificity in deciding whether to perform biopsy.

PAX5 deletion is common and concurrently occurs with CDKN2A deletion in B-lineage acute lymphoblastic leukemia

The PAX5 is essential in normal B-cell lymphopoiesis and deregulation of PAX5 function is believed to contribute to leukemogenesis in B-ALL. We performed a comprehensive study using FISH, G-banding and IHC to identify PAX5 deletion and expression in 102 CD19+ clinical B-ALL cases (79 children and 33 adults) and investigated its relationship with common cytogenetic changes including BCR-ABL1, ETV6-RUNX1 and MLL rearrangements, and CDKN2A deletion. The incidences of translocations and deletions were 2.5% and 10.0% in children, and 0.0% and 18.2% in adults, respectively. The incidence of PAX5 deletion was higher than those of BCR-ABL1 (8.9%) or MLL rearrangements (5.1%) in children and than that of MLL rearrangement (3.1%) in adults. Most patients with PAX5 deletion (83.3% of children and 100.0% of adults with PAX5 deletion) had concurrent CDKN2A deletion. PAX5 deletions were detected both in patients with positive and negative PAX5 expression. In this study, we found that PAX5 is a common target in leukemogenesis of B-ALL along with CDKN2A. Owing to its frequent deletion in B-ALL, PAX5 could be used as one of the molecular markers in diagnosis and monitoring of the disease. No correlation between expression of PAX5 and deletion of PAX5 suggests allele-specific regulation.

Prevalence of hepatitis E virus and sapovirus in post-weaning pigs and identification of their genetic diversity

Hepatitis E virus (HEV) and sapovirus (SaV) induce acute hepatitis and gastroenteritis, respectively, in humans. As pigs have been recognized as an important reservoir for these viruses, we evaluated the infection rates of both viruses using fecal samples collected from post-weaning pigs via RT-PCR methods. In the five swine farms assessed in this study, 3 farms were found to be HEV-positive and 4 farms were SaV-positive. The overall prevalence of HEV and SaV in the pigs was 17.0 and 23.1%, respectively. Phylogenetic tree analysis revealed that the isolated swine HEVs belonged to genotype 3 and the porcine SaVs belonged to genogroup III. This study proved that both HEV and SaV are prevailing in post-weaning pigs in Korea.

Sociodemographic and Smoking Behavioral Predictors Associated with Smoking Cessation According to Follow-up Periods: A Randomized, Double-blind, Placebo-controlled Trial of Transdermal Nicotine Patches

This study investigated sociodemographic and smoking behavioral factors associated with smoking cessation according to follow-up periods. In this randomized, double-blind, placebo-controlled trial of transdermal nicotine patches, subjects were a total of 118 adult male smokers, who were followed up for 12 months. Univariable logistic regression analysis and stepwise multiple logistic regression analyses were performed to identify the predictors of smoking cessation. The overall self-reported point prevalence rates of abstinence were 20% (24/118) at 12 months follow-up, and there was no significant difference in abstinence rates between placebo and nicotine patch groups. In the univariable logistic regression analysis, predictors of successful smoking cessation were the low consumption of cigarettes per day and the low Fagerstrom Test for Nicotine Dependence (FTND) scores (p<0.05) at 3, 6, and 12 months follow-up. In the stepwise multiple logistic regression analyses, predictors of successful smoking cessation, which were different according to the follow-up periods, were found to be the low consumption of cigarettes per day at the short-term and midterm follow-up (≤6 months), older age, and the low consumption of cigarettes per day at the long-term follow-up (12 months).

Ultrasonographic assessment of breast density

Ultrasonographic (US) assessment of breast density has the potential to provide a nonionizing method. This study was to prospectively evaluate intermodality and interobserver agreements for assessment of breast density between US and mammography. Institutional review board approval was obtained. Forty-one women (mean 52.1xa0years; range 25–72xa0years) with variable breast density consented to participate. Eight radiologists blinded to mammographic information performed breast US for all participants and assessed each breast density using four categories based on the proportion of the breast occupied by the fibroglandular tissue. All participants underwent full-field digital mammography and mammographic density was independently assessed by eight radiologists 2xa0weeks after US using the breast imaging reporting and data system (BI-RADS) 4-category system. Intermodality agreements between US and mammographic assessments and interobserver agreements among radiologists were assessed using kappa statistics (к) and intraclass correlation coefficients (ICCs). There was substantial intermodality agreement between the US and mammographic assessments of breast density (кxa0=xa00.65 and ICCxa0=xa00.80), and 68xa0% (222/328) of the assessments had exact agreement. When categories were dichotomized into fatty (categories 1 and 2) and dense (categories 3 and 4), 86xa0% (282/328) of the assessments had exact agreement (кxa0=xa00.71). The interobserver agreement for the US assessments of breast density was substantial (average кxa0=xa00.63, ICCxa0=xa00.82) and not significantly different from that for the mammographic assessments (average кxa0=xa00.74, ICCxa0=xa00.85) (Pxa0=xa00.701). US and mammography demonstrated substantial intermodality and interobserver agreement for assessment of breast density.