Clinical application of prospective whole-exome sequencing in the diagnosis of genetic disease: Experience of a regional disease center in South Korea.

INTRODUCTION: Next-generation sequencing helps clinicians diagnose patients with suspected genetic disorders. The current study aimed to investigate the diagnostic yield and clinical utility of prospective whole-exome sequencing (WES) in rare diseases. METHODS: WES was performed in 92 patients who presented with clinical symptoms suggestive of genetic disorders. The WES data were analyzed using an in-house developed software. The patients' phenotypic characteristics were classified according to the human phenotype ontology. RESULTS: WES detected 64 variants, 13 were classified as pathogenic, 26 as likely pathogenic, and 25 as variants of uncertain significance. In 57 patients with these variants, 30 were identified as causal variants. The diagnostic yield was higher in patients with abnormalities in joint mobility and skin morphology than in those with cerebellar hypoplasia/atrophy, epilepsy, global developmental delay, dysmorphic features/facial dysmorphisms, and chronic kidney disease/abnormal renal morphology. CONCLUSION: In this study, a WES-based variant interpretation system was employed to provide a definitive diagnosis for 28.3% of the patients suspected of having genetic disorders. WES is particularly useful for diagnosing rare diseases with symptoms that affect more than one system, when targeted genetic panels are difficult to employ.

Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.

15-Keto prostaglandin E2 induces heme oxygenase-1 expression through activation of Nrf2 in human colon epithelial CCD 841 CoN cells.

Prostaglandin E2 (PGE2) plays a key role in inflammation-associated carcinogenesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE2 to generate 15-keto PGE2. 15-PGDH has been known as a tumor suppressor in various malignancies including colon cancer. However, the molecular mechanisms underlying the tumor-suppressive function of 15-PGDH remain largely unresolved. In this study, we found that 15-keto PGE2 upregulated the expression of heme oxygenase-1 (HO-1), a representative antioxidative and anti-inflammatory enzyme, at both transcriptional and translational levels, in human colon epithelial CCD 841 CoN cells. A redox-sensitive transcription factor, NF-E2-related factor (Nrf2) plays a critical role in the regulation of HO-1 and other cytoprotective proteins. 15-Keto PGE2 induced translocation of Nrf2 into the nucleus and antioxidant response element-driven luciferase activity. Furthermore, the silencing of the Nrf2 gene abolished 15-keto PGE2-induced HO-1 expression in CCD 841 CoN cells. 15-Keto PGE2 activated AKT signaling, and the pharmacological AKT inhibitor, LY294002 suppressed the 15-keto PGE2-induced HO-1 expression. 15-Keto PGE2 generates the reactive oxygen species which is suppressed by the general antioxidant N-acetyl-l-cysteine. N-acetyl-l-cysteine treatment attenuated the 15-keto PGE2-induced phosphorylation of GSK3ß, transcriptional activity of Nrf2, and subsequently HO-1 expression. However, 13,14-dihydro-15-keto PGE2 lacking the α,ß-unsaturated carbonyl moiety failed to induce intracellular production of reactive oxygen species, HO-1 expression and nuclear translocation of Nrf2. In conclusion, 15-keto PGE2 induces HO-1 expression through Nrf2 activation in human colon epithelial cells.

Tumour size, volume, and marker expression during radiation therapy can predict survival of cervical cancer patients: a multi-institutional retrospective analysis of KROG 16-01.

OBJECTIVE: The aim of this multi-institutional study was to determine the prognostic impact of tumour parameters, such as tumour size (TS), tumour volume (TV), and marker expression, on survival during radiation therapy (RT) for cervical cancer patients. METHODS: A total of 231 patients with histologically confirmed cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) Ib2-IVa, were enrolled in this study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) and squamous cell carcinoma antigen (SCC-ag) analysis were performed twice, during RT and just before brachytherapy. RESULTS: The median follow-up time was 27.8months (range, 2-116months). Multivariate analysis revealed that stage (odds ratio [OR], 2.936 and 95% confidence interval [CI], 1.119-7.707; P=0.029), tumour volume reduction rate (TVRR) (OR, 3.435 and 95% CI, 1.062-11.106; P=0.039), and SCC-ag reduction rate (SCCRR) (OR, 5.104 and 95% CI, 1.769-14.727; P=0.003) were independently associated with overall survival (OS), while pre-RT TS (OR, 2.148 and 95% CI, 1.221-3.810; P=0.009), mid-RT TV (OR, 3.106 and 95% CI, 1.685-5.724; P<0.0001) and SCCRR (OR, 1.954 and 95% CI, 1.133-3.369; P=0.016) were associated with progression-free survival (PFS). Based on the prognostic factor analysis, patients with the highest prognostic risk score of 3 showed poorer overall survival and progression free survival than patients with lower prognostic risk scores. CONCLUSION: We identified that tumour parameters such as TVRR, SCCRR, pre-RT TS, and mid-RT TV areindependent and strong prognostic parameters for patients with cervical cancer receiving RT. This scoring system-based prognostic factor analysis could be used to help develop optimized treatment plans for cervical cancer patients during RT.

Molecular Basis of Alcohol-Related Gastric and Colon Cancer.

Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of ß-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

Maximum Standardized Uptake Value of Pelvic Lymph Nodes in [18F]-Fluorodeoxyglucose Positron Emission Tomography Is a Prognostic Factor for Para-Aortic Lymph Node Recurrence in Pelvic Node-Positive Cervical Cancer Treated With Definitive Chemoradiotherapy.

OBJECTIVES: This study aimed to identify prognostic factors for para-aortic lymph node (PALN) recurrence and their effect on survival outcomes in patients with pelvic node-positive squamous cell carcinoma (SCC) of the cervix treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: Of the 116 patients with biopsy-proven SCC of the uterine cervix who underwent primary CCRT from 2007 to 2012, 48 patients with pelvic LN metastasis detected by [F]-fluorodeoxyglucose positron emission tomography (FDG PET) were retrospectively analyzed. Patients with evidence of para-aortic lymphadenopathy were excluded. The whole pelvis was the standard irradiation field for all patients. The associations of age, stage, serum SCC antigen (SCC-Ag) level, maximum standardized uptake value (SUVmax), hemoglobin level, overall treatment time, adjuvant chemotherapy, and pelvic LN status with PALN recurrence and survival outcomes were evaluated. RESULTS: At a median follow-up of 34.0 months (range, 8-73 months), 10 (20.8%) patients had developed PALN recurrences. The relationship between pelvic LN FDG uptake and PALN recurrence was evaluated by the cutoff value (SUVmax = 3.85) determined by receiver operating characteristic curve analysis. The independent risk factors for PALN recurrence were FDG-avid pelvic LN (SUVPLN) greater than 3.85 (hazard ratio, 13.12; P = 0.025) and posttreatment SCC-Ag level greater than 2.0 (ng/mL) (hazard ratio, 20.69; P = 0.019). Patients with an SUVPLN greater than 3.85 were found to have significantly worse 5-year distant metastasis-free (51.0% vs 79.0%, P = 0.016) and progression-free survival (38.7% vs 67.3%, P = 0.011) than those with an SUVPLN less than or equal to 3.85. CONCLUSIONS: SUVPLN is a statistically significant prognostic factor of PALN recurrence and survival after definitive CCRT for pelvic node-positive SCC of the uterine cervix.

Elevated H3K18 acetylation in airway epithelial cells of asthmatic subjects.

BACKGROUND: Epigenetic adjustments of the chromatin architecture through histone modifications are reactive to the environment and can establish chromatin states which are permissive or repressive to gene expression. Epigenetic regulation of gene expression is cell specific and therefore, it is important to understand its contribution to individual cellular responses in tissues like the airway epithelium which forms the mucosal barrier to the inhaled environment within the lung. The airway epithelium of asthmatics is abnormal with dysregulation of genes such as epidermal growth factor receptor (EGFR), the ΔN isoform of the transcription factor p63 (ΔNp63), and signal transducer and activator of transcription 6 (STAT6), integral to differentiation, proliferation, and inflammation. It is important to establish in diseases like asthma how histone modifications affect tissue responses such as proliferation and differentiation. OBJECTIVES: To characterize the global histone acetylation and methylation status in the epithelium of asthmatic compared to healthy subjects and to identify the impact of these variations on genes involved in epithelial functions. METHODS: Whole lungs were obtained from healthy and asthmatic subjects (n = 6) from which airway epithelial cells (AECs) were isolated and airway sections were taken for analysis of histone lysine acetylation and methylation by immunohistochemistry. AECs were subjected to chromatin immunoprecipitation (ChIP) using anti-H3K18ac and anti-H3K4me2 antibodies followed by RT-PCR targeting ΔNp63, EGFR, and STAT6. AECs were also treated with TSA and changes in ΔNp63, EGFR, and STAT6 expression were determined. RESULTS: We identified an increase in the acetylation of lysine 18 on histone 3 (H3K18ac) and trimethylation of lysine 9 on histone 3 (H3K9me3) in the airway epithelium of asthmatic compared to healthy subjects. We found increased association of H3K18ac around the transcription start site of ΔNp63, EGFR, and STAT6 in AECs of asthmatics. However, we were unable to modify the expression of these genes with the use of the HDAC inhibitor TSA in healthy subjects. DISCUSSION: The airway epithelium from asthmatic subjects displays increased acetylation of H3K18 and association of this mark around the transcription start site of ΔNp63, EGFR, and STAT6. These findings suggest a complex interaction between histone modifications and gene regulation in asthma.

Serial changes in serum procalcitonin, interleukin 6, and C-reactive protein levels according to non-specific surgical stimulation.

BACKGROUND: The aim of this study is to investigate useful perioperative monitoring markers by comparing serial levels of serum procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein (CRP) in routine surgical circumstances. METHODS: In 285 surgeries of 277 patients, blood samples were obtained serially, at least three times per patient: within 48 h before surgery, 0-6 h after surgery (post-OP1), >6-28 h after surgery (post-OP2), and/or later (post-OP3). PCT, IL-6, and CRP were measured. Their demographic, operative, laboratory, and clinical data were collected retrospectively. RESULTS: The systemic inflammatory response syndrome (SIRS) (n=39) and sepsis (n=11) groups showed higher post-operative values than the non-SIRS group (n=233). Their maximum significant median levels were 8.96 vs. 0.21 µg/L for post-OP2 PCT, 743.1 vs. 85.8 ng/L for post-OP1 IL-6, and 103.4 vs. 49.0 mg/L for post-OP2 CRP. Among non-SIRS patients, 12 patients developed undesirable post-operative events, including secondary surgery and death. The highest area under receiver operator characteristic curves was 0.92 at post-OP1 PCT (cut-off, 0.1 µg/L; sensitivity, 91.7%; specificity, 78.7%), and the next highest was 0.84 at post-OP1 IL-6 (cut-off, 359 ng/L; sensitivity, 66.7%; specificity, 91.9%). All biomarkers were increased by non-specific surgical stimuli; however, post-OP1/post-OP2 PCT were <1.0 µg/L (90th percentile) except major abdominal surgeries. CONCLUSIONS: Post-OP1 PCT measurement may be useful as a post-operative monitoring marker for the following reasons: pre-operative values less than the cut-off regardless of pre-operative state (age, malignancy, and American Society of Anesthesiologists class); minimal influence from surgical stimulus; and prediction of post-operative undesirable events.

Activity of ERK regulates mucin 3 expression and is involved in undifferentiated Caco-2 cell death induced by 3-oxo-C12-homoserine lactone.

The signal molecule, 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), is similar to a mammalian hormone in bacteria. Although most studies have examined the effects of high 3-oxo-C12-HSL concentrations (>200 µM) on mammalian cellular functions because ~600 µM 3-oxo-C12-HSL can be secreted in biofilms of Pseudomonas aeruginosa grown in vitro, we previously showed that a low 3-oxo-C12-HSL concentration (30 µM) induces the apoptosis of undifferentiated Caco-2 cells through suppressing Akt activity. Here, we found that a low concentration of 3-oxo-C12-HSL-activated ERK1/2 in undifferentiated Caco-2 cells. Incubating cells with the ERK pathway inhibitor U0126 for 30 min alleviated the mucin 3 (MUC3) expression suppressed by 3-oxo-C12-HSL, and the upregulation of MUC3 expression induced by a 48-h incubation with U0126-reduced cell death. Thus, altered MUC3 expression caused by long-term attenuated ERK1/2 activity might correlate with the death of undifferentiated Caco-2 cells induced by 3-oxo-C12-HSL.

Measurement of anterior scleral curvature using anterior segment OCT.

PURPOSE: To investigate and validate methods for measuring the radius of anterior scleral curvature using anterior segment optical coherence tomography images. METHODS: Twenty-four volunteers were enrolled in this study. Anterior segment optical coherence tomography images, centered on horizontal/vertical limbus, including adjacent anterior sclera, were obtained in addition to conventional images centered on the optical axis. Central horizontal, nasal, and temporal optical coherence tomography images were consolidated to a new image for subsequent analyses. The reference points of limbal surface and three scleral points were marked nasally and temporally. The radius of a best-fit circle to the six scleral points was derived (the BFC [best-fit circle] method) and the radii of two circles, the centers of which are on the optical axis and pass through the points of the scleral surface at 2 mm from the limbus nasally and temporally, were calculated (the axial method). To assess the reliability and accuracy of each method, intraobserver and interobserver agreements were analyzed and the radii of contact lenses with known curvatures were measured. RESULTS: The mean (±SD) radius of a BFC was 13.12 (±0.80) mm. The mean (±SD) radius of nasal anterior scleral curvature (13.33 ± 1.12 mm) was significantly greater than that of temporal anterior scleral curvature (12.32 ± 0.77 mm) (paired samples t test, p < 0.001). The BFC and axial methods showed excellent intraobserver and interobserver agreements for measurements (intraclass correlation coefficient > 0.75, p < 0.001), whereas both methods showed a tendency to slightly underestimate the actual curvature of a rigid contact lens of known dimensions (-0.07 ± 0.13 mm [the BFC method] and -0.19 ± 0.07 mm [the axial method], Wilcoxon signed rank test, p = 0.173 and p = 0.028, respectively). CONCLUSIONS: Anterior segment optical coherence tomography is a valuable tool for measuring the radii of anterior scleral curvatures by image processing and mathematical calculation and can provide useful information in specific clinical situations such as designing scleral lenses.

Sinus irrigation as an adjunctive therapy for odontogenic maxillary sinusitis - an in-depth analysis.

BACKGROUND: Odontogenic maxillary sinusitis (OMS) is widely acknowledged in both the dentistry and otolaryngology fields. Recently, iatrogenic odontogenic maxillary sinusitis cases can be encountered frequently. The purpose of this study was to evaluate the effect of intraoral sinus irrigation using the small lateral window approach in patients with odontogenic maxillary sinusitis by comparing pre- and postoperative volumetric measurement of CBCT and symptoms. We surveyed 21 patients who visited the Oral and Maxillofacial Surgery Department at PNUDH from 2016 to 2022. All the patients' information was extracted from an electronic database. The patients with a follow-up period of 2 months or more were included. The three-dimensional volumetric measurement was performed using the ImageJ program (National Institute of Health, University of Wisconsin). RESULTS: Among 21 patients, 16 (76.1%) were male, and 5 (23%) were female. The most common type of surgery was general anesthesia (16 cases) in which oroantral fistula was present in 7 cases. In the causes of maxillary sinusitis, there were seven implant-related patients, five patients of tooth extraction, seven patients of bone grafting, and two patients in other groups. Radiographic opacity decreased by 40.15% after sinus irrigation especially in bone graft and tooth extraction cases. Clinically, symptoms improved in 17 patients (80.9%). CONCLUSION: By this study, it can be concluded that maxillary sinus irrigation using the small lateral window approach is a clinically and radiologically effective treatment method for odontogenic maxillary sinusitis.

Establishment and characterization of six canine hepatocellular carcinoma cell lines.

Background: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. Methods: The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). Results: We established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial-mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Conclusion: Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

Coagulation Testing in Real-World Setting: Insights From a Comprehensive Survey.

The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea.Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022.The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea.Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing.

Contribution of the 7ß-hydroxysteroid dehydrogenase from Ruminococcus gnavus N53 to ursodeoxycholic acid formation in the human colon.

Bile acid composition in the colon is determined by bile acid flow in the intestines, the population of bile acid-converting bacteria, and the properties of the responsible bacterial enzymes. Ursodeoxycholic acid (UDCA) is regarded as a chemopreventive beneficial bile acid due to its low hydrophobicity. However, it is a minor constituent of human bile acids. Here, we characterized an UDCA-producing bacterium, N53, isolated from human feces. 16S rDNA sequence analysis identified this isolate as Ruminococcus gnavus, a novel UDCA-producer. The forward reaction that produces UDCA from 7-oxo-lithocholic acid was observed to have a growth-dependent conversion rate of 90-100% after culture in GAM broth containing 1 mM 7-oxo-lithocholic acid, while the reverse reaction was undetectable. The gene encoding 7ß-hydroxysteroid dehydrogenase (7ß-HSDH), which facilitates the UDCA-producing reaction, was cloned and overexpressed in Escherichia coli. Characterization of the purified 7ß-HSDH revealed that the kcat/Km value was about 55-fold higher for the forward reaction than for the reverse reaction, indicating that the enzyme favors the UDCA-producing reaction. As R. gnavus is a common, core bacterium of the human gut microbiota, these results suggest that this bacterium plays a pivotal role in UDCA formation in the colon.

Delirium After Traumatic Brain Injury: Prediction by Location and Size of Brain Lesion.

OBJECTIVE: To examine (1) the location of brain lesion that would predict post-traumatic delirium and (2) the association between volume of brain lesion and occurrence of delirium in patients with traumatic brain injury (TBI). METHODS: A retrospective study was conducted by reviewing medical records of 68 TBI patients, categorized into two groups: the delirious group (n=38) and non-delirious group (n=30). The location and volume of TBI were investigated with the 3D Slicer software. RESULTS: The TBI region in the delirious group mainly involved the frontal or temporal lobe (p=0.038). All 36 delirious patients had brain injury on the right side (p=0.046). The volume of hemorrhage in the delirious group was larger by about 95 mL compared to the non-delirious group, but this difference was not statistically significant (p=0.382). CONCLUSION: Patients with delirium after TBI had significantly different injury site and side, but not lesion size compared to patients without delirium.

The Oxford classification as a predictor of prognosis in patients with IgA nephropathy.

BACKGROUND: In 2009, the Oxford classification was developed as a pathological classification system for immunoglobulin A nephropathy (IgAN) to predict the risk of disease progression. The aim of this retrospective study was to evaluate the clinical and pathologic relevance of the Oxford classification in Korean patients with a pathologic diagnosis of IgAN. PATIENTS AND METHODS: We reviewed the renal pathology archives from January 2000 to December 2006 at Seoul St Mary's Hospital in Korea and identified 273 patients, who were diagnosed as having IgAN. We enrolled 197 patients who were available for further clinicopathologic analysis. All cases of IgAN were categorized according to the WHO classification, the semiquantitative classification and the Oxford classification. These pathologic classifications were compared. The clinical and laboratory findings at the time of biopsy were compared with those at the end of the follow-up according to the Oxford classification. RESULTS: When three pathologic classifications were compared, M1, S1, E1, T1 or T2 were associated with a higher score in the activity index. S1, T1 or T2 were associated with a higher score in the chronicity index and a higher grade in the WHO classification. The clinical and laboratory findings were compared according to the Oxford classification. At the time of biopsy, the proteinuria in patients with M1 was more than that of M0 (P = 0.035). At the end of follow-up, the number of antihypertensive drugs taken among patients with M1 was greater than that of patients with M0 (P = 0.001). At the time of biopsy, the proteinuria of patients with S1 was greater than that of S0 patients (P = 0.009). At the end of follow-up, the number of patients who received immunosuppressants was increased as the grade of T increased (P = 0.000). At the end point of the follow-up, the estimated glomerular filtration rate (eGFR) decreased as the grade of T increased (P = 0.008). The time-average proteinuria after adjusting the initial proteinuria increased significantly with increasing degree of T (P = 0.000). Levels of tubular atrophy/interstitial fibrosis were predictive for survival from end-stage renal disease or of having a 50% reduction of eGFR. CONCLUSION: The pathologic variables of the Oxford classification correlated significantly with other classifications (the WHO classification and the semiquantitative classification). The Oxford classification is a simple method for predicting renal outcome and differentiating between active and chronic lesions. We suggest that the Oxford classification offers an advantage for determining treatment policy for patients with IgAN.