Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society.

BACKGROUND: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody-drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. METHODS: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan-Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. RESULTS: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019). CONCLUSIONS: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Postnatal Imaging for Prediction of Outcome in Patients with Left-sided Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate associations between postnatal imaging features and outcome of left-sided congenital diaphragmatic hernia, as defined by overall survival and a requirement for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Newborns diagnosed prenatally with left-sided congenital diaphragmatic hernia between January 2013 and September 2021 were studied retrospectively. The esophageal deviation index was newly defined as the largest diameter from the midline to deviated gastric tube divided by the largest transverse diameter of the thoracic cavity on the radiograph. Regression analyses were performed to identify postnatal imaging features associated with overall survival and a requirement for ECMO. The predictive power (ie, area under the curve [AUC] of a time-dependent receiver operating characteristic curve) of prenatal, postnatal, and intraoperative findings for predicting survival were calculated. RESULTS: Ninety-seven patients (54 males; mean gestational age, 38.3 ± 1.9 weeks; mean birth weight, 2956.5 ± 540.0 g) were analyzed. The esophageal deviation index (adjusted hazard ratio [HR], moderate [≥0.19 to <0.24], 6.427 [P = .029]; severe [≥0.24], 33.007 [P < .001]) and right pneumothorax (adjusted HR, 8.763; P = .002) were associated with overall survival and with a requirement for ECMO. Liver herniation on postnatal ultrasound also was associated with overall survival (P < .001) and need for ECMO (P = .001). In addition, the AUC for prediction of 1-year survival from postnatal ultrasound was comparable with that of prenatally or intraoperatively detected liver herniation (0.93; 95% CI, 0.88-0.97). CONCLUSIONS: The esophageal deviation index, right pneumothorax, and liver herniation observed by postnatal imaging have prognostic value in patients with left-sided congenital diaphragmatic hernia.

Fetal cardiac parameters for predicting postnatal operation type of fetuses with tetralogy of Fallot.

BACKGROUND: To assess fetal cardiac parameters predictive of postnatal operation type in fetuses with tetralogy of Fallot (TOF). METHODS: Echocardiographic data obtained in the second and third trimesters were retrospectively reviewed for fetuses diagnosed with TOF between 2014 and 2018 at Asan Medical Center. The following fetal cardiac parameters were analyzed: 1) pulmonary valve annulus (PVA) z-score, 2) right pulmonary artery (RPA) z-score, 3) aortic valve annulus (AVA) z-score, 4) pulmonary valve peak systolic velocity (PV-PSV), 5) PVA/AVA ratio, and 6) RPA/descending aorta (DAo) ratio. These cardiac parameters were compared between a primary corrective surgery group and a palliative shunt operation followed by complete repair group. RESULTS: A total of 100 fetuses with TOF were included. Only one neonatal death occurred. Ninety patients underwent primary corrective surgery and 10 neonates underwent a multistage surgery. The PVA z-score, RPA z-score, and RPA/DAo ratio measured in the second trimester and the PVA z-score, RPA z-score, and PVA/AVA raio measured in the third trimester were significantly lower in the multistage surgery group, while the PV-PSV as measured in both trimesters were significantly higher in the multistage surgery group. CONCLUSION: Fetal cardiac parameters are useful for predicting the operation type necessary for neonates with TOF.

Extremely Rare Case of Fetal Anemia Due to Mitochondrial Disease Managed with Intrauterine Transfusion.

This report describes a rare case of fetal anemia, confirmed as a mitochondrial disease after birth, treated with intrauterine transfusion (IUT). Although mitochondrial diseases have been described in newborns, research on their prenatal features is lacking. A patient was referred to our institution at 32 gestational weeks owing to fetal hydrops. Fetal anemia was confirmed by cordocentesis. After IUT had been performed three times, the anemia and associated fetal hydrops showed improvement. However, after birth, the neonate had recurrent pancytopenia and lactic acidosis. He was eventually diagnosed with Pearson syndrome and died 2 months after birth. This is the first case report of fetal anemia associated with mitochondrial disease managed with IUT.

Inhibition of STAT3 enhances sensitivity to tamoxifen in tamoxifen-resistant breast cancer cells.

BACKGROUND: The mechanisms of endocrine resistance are complex, and deregulation of several oncogenic signalling pathways has been proposed. We aimed to investigate the role of the EGFR and Src-mediated STAT3 signalling pathway in tamoxifen-resistant breast cancer cells. METHODS: The ER-positive luminal breast cancer cell lines, MCF-7 and T47D, were used. We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. Cell viability was determined using an MTT assay, and protein expression levels were determined using western blot. Cell cycle and annexin V staining were analysed using flow cytometry. RESULTS: TamR cells showed decreased expression of estrogen receptor and increased expression of EGFR. TamR cells showed an acceleration of the G1 to S phase transition. The protein expression levels of phosphorylated Src, EGFR (Y845), and STAT3 was increased in TamR cells, while phosphorylated Akt was decreased. The expression of p-STAT3 was enhanced according to exposure time of tamoxifen in T47D cells, suggesting that activation of STAT3 can cause tamoxifen resistance in ER-positive breast cancer cells. Both dasatinib (Src inhibitor) and stattic (STAT3 inhibitor) inhibited cell proliferation and induced apoptosis in TamR cells. However, stattic showed a much stronger effect than dasatinib. Knockdown of STAT3 expression by siRNA had no effect on sensitivity to tamoxifen in MCF-7 cells, while that enhanced sensitivity to tamoxifen in TamR cells. There was not a significant synergistic effect of dasatinib and stattic on cell survival. TamR cells have low nuclear p21(Cip1) expression compared to MCF-7 cells and inhibition of STAT3 increased the expression of nuclear p21(Cip1) in TamR cells. CONCLUSIONS: The EGFR and Src-mediated STAT3 signalling pathway is activated in TamR cells, and inhibition of STAT3 may be a potential target in tamoxifen-resistant breast cancer. An increase in nuclear p21(Cip1) may be a key step in STAT3 inhibitor-induced cell death in TamR cells.

Prognostic value of noggin protein expression in patients with resected gastric cancer.

BACKGROUND: Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. METHODS: A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. RESULTS: RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P <  0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P <  0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35-0.97, P <  0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81-2.26, P = 0.251). CONCLUSIONS: Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.

Ultrasonographic evaluation of ovarian mass for predicting malignancy in pregnant women.

OBJECTIVE: The purpose of this study is to compare ultrasonographic ovarian mass scoring systems in pregnant women. STUDY DESIGN: This multicenter study included women with an ovarian mass during pregnancy who were evaluated using ultrasound and underwent surgery in 11 referral hospitals. The ovarian mass was evaluated and scored using three different scoring systems(International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adnexa[IOTA ADNEX], Sassone, and Lerner). The final diagnosis was made histopathologically. Receiver operating characteristic(ROC) curves were generated for each scoring system. RESULTS: During the study period, 236 pregnant women underwent surgery for an ovarian mass, including 223 women(94.5%) with a benign ovarian mass and 13 women(5.5%) with a malignant ovarian mass. Among 10 ultrasound image findings, six findings were different between benign and ovarian masses(maximal diameter of mass, maximal diameter of solid mass, wall thickness of mass, inner wall structure, thickness of septations, and papillarity). In all three scoring systems, the ovarian mass scores were significantly higher in malignant masses than in benign masses, with the highest area under the ROC curve(AUROC) in the Sassone scoring system(AUROC: 0.831 for Sassone, 0.710 for Lerner vs 0.709 for IOTA ADNEX; p < 0.05, between the Sassone and Lerner/ IOTA ADNEX). A combined model was developed with the six different ultrasound findings, and the AUROC of the combined model was 0.883(p = not significant between the combined model and Sassone). CONCLUSION: In pregnant women, malignant ovarian tumors can be predicted with high accuracy using either the Sassone scoring system or the combined model.

Mid-pregnancy PM2.5 exposure affects sex-specific growth trajectories via ARRDC3 methylation.

Prenatal particulate matter <2.5 µm (PM2.5) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.

Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center's experience.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement. METHODS: We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors. RESULTS: A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50. CONCLUSIONS: The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.

Novel Technique for the Measurement of Fetal Right Modified Myocardial Performance Index Using Synchronized Images of Right Ventricular Inflow and Outflow and Clinical Application to Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the reproducibility of the fetal right modified myocardial performance index (Mod-MPI) obtained by synchronizing the inflow and outflow images of the right ventricle (RV) and to evaluate its feasibility through clinical application to twin-to-twin transfusion syndrome (TTTS). METHODS: We prospectively evaluated 77 normal fetuses. Two experienced operators individually measured the right Mod-MPI using two different methods: (1) separate recording of the RV inflow and outflow using pulsed-wave Doppler (conventional method) and (2) synchronization of RV inflow and outflow images using the MPI + ™ function based on the closure click of the pulmonary valve (new method). To evaluate the clinical utility of the new method, we measured the right Mod-MPI in 33 TTTS fetuses using the new method before and after the fetoscopic laser coagulation (FLC). RESULTS: There was no statistical difference in Mod-MPI values between the two methods (p = .242). For both operators, the intra- and interoperator reproducibility of Mod-MPI was high with both methods (ICCs >0.950). Among the components of Mod-MPI measured using the new method, ejection time showed the highest reproducibility, whereas isovolumetric relaxation time demonstrated the lowest reproducibility. In TTTS fetuses, the Mod-MPI significantly decreased after FLC in recipients, and there was no difference in MPI values before and after FLC in donors. CONCLUSION: Right Mod-MPI measurement after the synchronization of RV inflow and outflow images is a reliable technique for evaluating fetal right cardiac function. This novel method can also independently evaluate the systolic and diastolic functions of the right heart.

Prenatal PM2.5 exposure and vitamin D-associated early persistent atopic dermatitis via placental methylation.

BACKGROUND: The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 µm to 2.5 µm (PM2.5) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM2.5 exposure and AD in an offspring. OBJECTIVE: To determine the critical windows of prenatal PM2.5 exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring. METHODS: Mother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM2.5 was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician's diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta. RESULTS: PM2.5 exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM2.5 exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM2.5 and low CB vitamin D. CONCLUSION: Higher PM2.5 during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.

Female reproductive factors and the risk of Parkinson's disease: a nationwide cohort study.

There are conflicting finds in the literature regarding the association of female estrogen status and the incidence of Parkinson's disease (PD). We aimed to investigate whether female reproductive factors are associated with PD. Using the Korean National Health Insurance System database, 4,729,546 postmenopausal women without PD were identified. The new incidence of PD was defined as subjects with an ICD-10 code for PD (G20) and with a rare intractable disease registration code for PD (V124). The Cox proportional hazard models were used to evaluate the associations of various reproductive factors with incidence of PD. During the median follow-up of 5.84 years, 20,816 individuals were diagnosed with PD. An increased risk of PD was observed in subjects with a later age at menarche (≥ 17 years) compared with reference subjects (13 years ≤ age at menarche ≤ 14 years) (adjusted hazard ratio, aHR 1.10, 95% confidence interval, CI 1.05-1.16). As age at menopause increased, risk of PD decreased (P for trend 0.019). Consistently, decreased risk of PD was observed (aHR 0.91, 95% CI 0.85-0.96) in subjects with longer duration of fertility (≥ 40 years of age) compared with shorter duration of fertility (< 30 years of age). Hormone replacement therapy and oral contraceptives independently increased the risk of PD by 17% and 7%, respectively. Female reproductive factors are independent risk factors for PD, with higher risk associated with shorter lifetime exposure to endogenous estrogen.

Fatal hemolytic disease of the fetus and newborn caused by anti-Jra antibody: A case report and literature review.

The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.

Comparison of the Prognostic Factors of Fetuses With Congenital Pulmonary Airway Malformations According to Type.

OBJECTIVES: To compare the prognostic factors of fetuses with microcystic and macrocystic congenital pulmonary airway malformations (CPAMs). METHODS: We retrospectively evaluated fetuses with CPAMs at Asan Medical Center. The CPAM size, mass effect, and maximum cyst size in macrocystic CPAMs were evaluated prenatally. The adverse postnatal outcomes, including respiratory symptoms, mechanical ventilation, and surgery, were evaluated. RESULTS: In 118 cases, 2 fetal deaths and 1 neonatal death occurred. All cases of fetal hydrops and complete regression after birth were in the macrocystic and microcystic CPAM groups, respectively. Twenty-four neonates (20.7%) had respiratory symptoms, and 18 (15.5%) required mechanical ventilation. Sixty-three neonates (54.3%) underwent surgery, of whom 21 (33.3%) required surgery in the neonatal period. The maximum congenital pulmonary airway malformation volume ratio was significantly associated with all postnatal outcomes (P < .05), and the optimal cutoff values were lower for respiratory symptoms, mechanical ventilation, and neonatal surgery in the macrocystic CPAMs. The maximum cyst size was also associated with all postnatal outcomes in macrocystic CPAMs (P < .05). CONCLUSIONS: Different cutoff values for the maximum congenital pulmonary airway malformation volume ratio should be applied according to the CPAM type for the prediction of postnatal outcomes. The maximum cyst size can also be a useful prognostic factor in macrocystic CPAMs.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth.

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB). METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy. RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633-5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915-405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy. CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Prenatal sonographic markers of the outcome in fetuses with bronchopulmonary sequestration.

PURPOSE: To evaluate the prenatal sonographic predictive markers of the outcome in fetuses with bronchopulmonary sequestration (BPS). METHODS: BPS size and diameter of the feeding artery (FA) were measured prenatally and postnatally. Velocity of the FA and the left ventricular-modified myocardial performance index (LV mod-MPI) were also evaluated prenatally. RESULTS: Forty-seven women were included in the study. Mean gestational age, mass size, diameter and velocity of the FA, and LV mod-MPI at prenatal diagnosis were 23.5 ± 2.2 weeks, 3.6 ± 8.3 cm, 2.3 ± 0.6 mm, 46.6 ± 15.4 cm/s, and 0.46 ± 0.06, respectively. Mean mass diameter and FA diameter measured on postnatal CT examinations were 3.8 ± 1.0 cm and 2.3 ± 0.7 mm, respectively. Five patients had respiratory symptoms after birth. Twenty children (43%) underwent or were scheduled to undergo mass excision, and the remaining 27 (57%) were doing well without any intervention. There was no neonatal death. LV mod-MPI at diagnosis, the FA diameter after birth and the serial change in the FA size were significantly associated with postnatal mass excision. CONCLUSION: The FA diameter and LV mod-MPI may be additional markers for predicting whether fetuses with BPS should undergo mass excision in early childhood or conservative care.

Prospective clinical evaluation of Momguard non-invasive prenatal test in 1011 Korean high-risk pregnant women.

Clinical performance of the Momguard non-invasive prenatal test (NIPT) was evaluated in a cohort of Korean pregnant women. The foetal trisomies 21, 18 and 13 (T21, T18 and T13) were screened by low-coverage massive parallel sequencing in the maternal blood. Among the 1011 confirmed samples, 32 cases (3.2%) had positive NIPT results. Of these positive cases, 20 cases of T21, all cases of T18 and two cases of T13 had concordant karyotype findings. Only one case out of the remaining 979 negative NIPT samples showed a false negative result. The overall sensitivity and specificity of Momguard to detect the three chromosomal aneuploidies were 96.8% and 99.8%, respectively. Momguard is a clinically useful tool for the detection of T21, T18 and T13 in singleton pregnancy. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.Impact StatementWhat is already known on this subject? The NIPT approach using massive parallel sequencing (MPS) showed high sensitivity and specificity in various clinical studies. These results are based on analysis systems using their own bioinformatics algorithms.What the results of this study add? When this NIPT technology was introduced in Korea, the first biological specimens collected in Korea were transported overseas for processing in overseas laboratories and analysed by other country's analysis methods. We needed our own NIPT algorithm and developed Momguard NIPT for the first time in Korea. This study attempted to evaluate this Momguard NIPT protocol prospectively in a large number of samples obtained from three Korean hospitals.What the implications are of these findings for clinical practice and/or further research? The overall sensitivity and specificity to identify T13, T18 and T21 were 96.8% and 99.8%, respectively. These accuracy values were comparable to that of other studies. From this study, we found that Momguard is a clinically useful tool for the detection of three chromosomal aneuploidies. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.

QKI, a miR-200 target gene, suppresses epithelial-to-mesenchymal transition and tumor growth.

The microRNA-200 (miR-200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well-known regulators of the epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR-200 family members control RNA-binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR-200a and miR-200b could recognize QKI 3'-UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR-200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR-200 overexpression, and the 3'-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR-200 form a negative feedback loop to maintain homeostatic responses to EMT-inducing signals.

Prognostic value of Dickkopf-1 and ß-catenin expression in advanced gastric cancer.

BACKGROUND: Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. METHODS: In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. RESULTS: DKK1 expression was high in 73 (46.2%) patients, while ß-catenin expression was positive in 51 (32.3%) patients. The expression of DKK1 was positively correlated with that of ß-catenin (P < 0.001). The combined expression of DKK1 and ß-catenin was significantly associated with high N stage (N2 and N3) (P = 0.042). In addition, patients with high DKK expression demonstrated poorer overall (OS) (P < 0.001) and disease-free survival (DFS) (P = 0.001). However, there were no differences between high DKK1 expression with ß-catenin positivity and high DKK1 expression with ß-catenin negativity (OS, P = 0.379: DFS, P = 0.255). Multivariate analysis revealed that high DKK1 alone or high DKK1 with ß-catenin positivity were independent prognostic factors for both OS (high DKK1: hazard ratio [HR], 2.130; 95% confidence interval [CI]; 1.370-3.312, P = 0.001; high DKK1 with ß-catenin positivity: HR, 2.140; 95% CI, 1.343-3.409: P = 0.001) and DFS (high DKK1: HR, 2.092; 95% CI, 1.180-3.708; P = 0.012; high DKK1 with ß-catenin positivity: HR, 2.357; 95% CI, 1.291-4.306; P = 0.005). CONCLUSION: Our results indicate that high DKK1 expression regardless of ß-catenin positivity is a crucial prognostic factor for predicting tumor recurrence and survival in patients with resected AGC.

Perinatal Outcomes of Fetal Lower Urinary Tract Obstruction After Vesicoamniotic Shunting Using a Double-Basket Catheter.

OBJECTIVES: To evaluate the perinatal survival and renal function of fetuses with lower urinary tract obstruction (LUTO) who underwent vesicoamniotic shunting using a double-basket catheter METHODS: We retrospectively reviewed 32 fetuses with LUTO who underwent vesicoamniotic shunting using a double-basket catheter between 1998 and 2013. RESULTS: Among the 32 fetuses examined, 5 died because of termination of pregnancy, and 2 died in utero. The median gestational age at diagnosis was 15.5 (range, 10.0-27.3) weeks, and that at initial shunting was 17.1 (range, 12.3-32.2) weeks. Shunt dislocation or occlusion occurred in 18 of 42 procedures (42.8%). The median gestational age at delivery for the 25 live births was 35.5 (range, 28-40) weeks. Postnatal diagnosis revealed posterior urethral valves in 15 fetuses, a cloacal anomaly in 7, and urethral stenosis in 3. Three neonatal deaths occurred, resulting in an overall perinatal survival rate of 68.8% (22 of 32). The rates of normal renal function were 40.6% (13 of 32) at 28 days and 40% (10 of 25) at 2 years after birth. The absence of oligohydramnios after shunting was the only prognostic factor for normal renal function at 2 years (P < .05). CONCLUSIONS: Vesicoamniotic shunting may be helpful for fetuses with LUTO.