Young Hyeh Ko

Sungkyunkwan University, Sŏul, Seoul, South Korea

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Publications (124)392.6 Total impact

  • Mineui Hong · Young Hyeh Ko
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    ABSTRACT: Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self-limited, ulcerative lesion of the oral cavity. The pathogenesis of this condition is unknown but falls within the spectrum of CD30(+) T-cell lymphoproliferative disease (LPD) of the oral mucosa. We report two cases in children diagnosed with EUOM and CD30(+) T-cell LPD. Retrospective analysis revealed that a majority of infiltrated atypical T-cells were positive for Epstein-Barr virus (EBV). This finding suggests that the pathogenesis and etiology of EUOM or CD30(+) T-cell LPD occurring in children are different from those in adults. CD30(+) T-cell LPD in children is a manifestation of EBV-positive T-cell LPD and should therefore be distinguished from EUOM or CD30(+) T-cell LPD in adults.
    09/2015; DOI:10.4132/jptm.2015.07.13
  • Haematologica 09/2015; DOI:10.3324/haematol.2015.133074 · 5.81 Impact Factor
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    ABSTRACT: Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification, primarily H3K27me3, and deregulation of PRC pathways leads to tumorigenesis. In the present study, activation of PRC2, H3K27me3, and BMI1 was investigated by immunohistochemistry in 175 cases of T and natural killer (NK) cell lymphoma. Activation of PRC proteins was analyzed according to c-MYC activation, Epstein-Barr virus (EBV) infection, CD30 activation, and survival. Among all T and NK cell lymphomas, high expression rates of 54.7 % for EZH2, 33.3 % for SUZ12, 85.7 % for EED, 40.5 % for H3K27me3, and 30.9 % for BMI1 were discovered. Activation of PRC2, H3K27me3, and BMI1 showed positive correlations (P < 0.05). Activation of c-MYC was associated with activation of SUZ12 and triple coactivation of all PRC2 protein subunits (EZH2(high)/SUZ12(high)/EED(high)) (P < 0.05). In EBV-positive tumors, activation of EZH2 and H3K27me3 showed greater association (P < 0.05). H3K27me3 and BMI1 showed a negative association in tumors expressing CD30 (P < 0.05). With respect to survival, BMI1 activation was independently associated with poor prognosis in T and NK cell lymphomas (P = 0.002). In conclusion, T and NK cell lymphomas were associated with activation of PRC pathway markers, for which c-MYC activation and EBV infection could be suggested as possible causes. PRC pathway markers may be potential therapeutic targets and prognostic markers in T and NK cell lymphoma.
    Tumor Biology 09/2015; DOI:10.1007/s13277-015-3977-y · 3.61 Impact Factor
  • Jung Yong Hong · Young Hyeh Ko · Seok Jin Kim · Won Seog Kim
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    ABSTRACT: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an EBV-positive monoclonal large B-cell proliferative disease that arises in elderly patients older than 50 years. Updated knowledge on geographical/ethnical variations in the prevalence and prognostic impact of EBV positivity, the genetic mechanisms of lymphomagenesis, and the validity of the disease is available. The poor prognostic impact of EBV positivity is consistent among Asian populations, but not in Western populations. CD30 may be associated with this geographical/ethnical variation. Gene expression analyses have confirmed the enhanced activity of the NF-κB and JAK/STAT pathways and more frequent expression of CD30 in EBV-positive DLBCL of the elderly. A substantial proportion of cases of EBV-positive DLBCL of the elderly occur in young immunocompetent adults; moreover, EBV-positive DLBCL in young adults has a distinct clinical course compared with EBV-positive DLBCL of the elderly. Further research is anticipated, as follows: first, identifying geographical/ethnical differences in gene expression profiles and CD30 coexpression in EBV-positive DLBCL of the elderly; second, feasibility of the revision of the current disease entity confined to elderly patients; and third, novel therapeutic approaches targeting CD30 and the NF-κB and JAK/STAT pathways in EBV-positive DLBCL of the elderly.
    Current opinion in oncology 09/2015; 27(5):392-398. DOI:10.1097/CCO.0000000000000210 · 4.47 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):3897-3897. DOI:10.1158/1538-7445.AM2015-3897 · 9.33 Impact Factor
  • International journal of radiation oncology, biology, physics 07/2015; DOI:10.1016/j.ijrobp.2015.07.2267 · 4.26 Impact Factor
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    ABSTRACT: Endoscopic findings of extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, are heterogeneous, but not fully understood. The objective of this study was to evaluate the role of nasal endoscopic examination and its implications for treatment of stage I/II ENKTL. This retrospective study included 60 consecutive patients diagnosed with stage I/II ENKTL, nasal type, from 2000 to 2011. The endoscopic findings were classified into early (45%) and advanced (55%) lesions. Furthermore, the primary tumor extent assessed by endoscopy was significantly correlated with the radiologic imaging (p < 0.001). The results of univariate analysis showed that the patients with advanced lesions had worse overall survival (p = 0.004) and disease-free survival (p = 0.001) than those with early lesions. In multivariate analysis, advanced lesions on nasal endoscopy was an independent prognostic factor (p = 0.024; hazard ratio 5.29; 95% confidence interval, 1.25-22.39). We found that nasal endoscopic findings were important prognostic factors in stage I/II ENKTL, nasal type, suggesting that comprehensive endoscopic evaluation of primary tumor should be performed in this setting. © 2015 ARS-AAOA, LLC.
    International Forum of Allergy and Rhinology 06/2015; DOI:10.1002/alr.21564 · 2.37 Impact Factor
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    ABSTRACT: The purpose of the present study was to compare microarray gene-expression profiling data between primary central nervous system (CNS) lymphoma and non-CNS lymphomas. We performed whole-genomic cDNA-mediated annealing, selection and ligation assay with 177 formalin-fixed paraffin-embedded tumor samples. We identified 20 differentially expressed genes out of which 5 were predominantly expressed in CNS DLBCL compared to non-CNS DLBCL (C16orf59, SLC16A9, HPDL, SPP1, and MAG). SLC16A9 may be involved in aerobic glycolysis of malignant tumors. The alteration in gene expression of SPP1 in primary CNS lymphoma is involved in biological activity, such as CNS tropism, B-cell migration, proliferation, and aggressive clinical behavior. MAG may be an important adhesion molecule that contributes to perineural cancer invasion. Genomic differences between CNS and non-CNS DLBCL exist and the most prominent genes are SPP1 and MAG. SPP1 may play a key role in CNS tropism of primary CNS lymphoma. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 06/2015; 35(6):3333-3340. · 1.83 Impact Factor
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    ABSTRACT: The Glasgow Prognostic Score (GPS) measures inflammation and proves its prognostic value in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL) which is commonly combined with inflammatory lesion. Given inflammatory chemokines play an important role in tumor progression, we hypothesized that chemokines might influence ENKTL aggressiveness through interaction with their receptors in the tumor tissue. We measured the serum levels of C-X-C motif ligand 13 (CXCL13) in 69 patients with ENKTL who received non-anthracycline-based chemotherapy and/or concurrent chemoradiotherapy because CXCL13 is thought to have a pro-tumor effect through interaction with its receptor, the C-X-C chemokine receptor 5 (CXCR5). We analyzed the association of serum CXCL13 with the GPS, and their prognostic relevance. The levels of CXCL13 were measured using a multiplex chemokine assay on archived frozen serum samples. Patients were categorized into high and low CXCL13 groups if they had CXCL13 levels above or below the median value of 29.1 pg/mL, respectively. The high CXCL13 group and grouping by the GPS showed a significant association with poor progression-free survival. The elevated serum levels of CXCL13 were also significantly associated with a high score of the GPS. High CXCL13 levels and GPS were significantly associated with high tumor burden predicting poor prognosis including stages III/IV, extranasal presentation, bone marrow invasion, and presence of Epstein-Barr virus (EBV) DNA in blood. Furthermore, serum CXCL13 and GPS discriminated patients at risk of treatment failure among patients with low tumor burden (stage I/II) and non-detectable EBV DNA. Serum levels of CXCL13 were associated with the prognostic value of GPS. Grouping by the serum CXCL13 might predict survival outcomes in patients with ENKTL, suggesting that it is a potential therapeutic target.
    Journal of Hematology & Oncology 05/2015; 8(1):49. DOI:10.1186/s13045-015-0142-4 · 4.81 Impact Factor
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    ABSTRACT: Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin lymphoma that more frequently occurs in East Asia and Latin America. Even though its molecular background has been discussed in the last few years, the current knowledge does not explain the disease pathogenesis in most cases of ENKL. Here, we performed multiple types of next-generation sequencing on 34 ENKL samples, including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines), targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and 4 cancer cell lines). Mutations were found most frequently in 3 genes, STAT3, BCOR, and MLL2 (which were present in 9, 7, and 6 cancer samples, respectively), whereas there were only 2 cases of JAK3 mutation. In total, JAK/STAT pathway- and histone modification-related genes accounted for 55.9% and 38.2% of cancer samples, respectively, and their involvement in ENKL pathogenesis was also supported by gene expression analysis. In addition, we provided 177 genes upregulated only in cancer tissues, which appear to be linked with angiocentric and angiodestructive growth of ENKL. In this study, we propose several novel driver genes of ENKL, and show that these genes and their functional groups may be future therapeutic targets of this disease.
    Oncotarget 04/2015; 6(19). DOI:10.18632/oncotarget.3776 · 6.36 Impact Factor
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    ABSTRACT: Background: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway of B-cell receptor (BCR) signaling pathway and plays a crucial role in the pathogenesis of B-cell lymphoma. However, there have been preclinical data showing PI3K/AKT pathway activation in T-cell lymphoma, with in different mechanisms from those in B-cell lymphoma. In this study, we investigated the impact of p-AKT expression on clinical outcomes of peripheral T-cell lymphoma (PTCL). Materials and methods: We analyzed 63 patients with PTCL [PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) or extranodal natural kiler T-cell lymphoma (NKTCL)]. To define the clinical implications of p-AKT expression in PTCL, we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression. Results: Based on a cutoff value of the upper limit of the third quartile (Q3) of the AU, 12 patients were classified into the high p-AKT group, while the remaining 51 patients were classified into the low p-AKT group. The overall response rate to frontline chemotherapy was significantly lower in the high p-AKT group than in the low p-AKT group (20.0% vs. 71.1%, p=0.004). The high p-AKT group showed substantially worse overall survival (OS) (median OS=2.3 vs. 25.2 months, p<0.001) and progression-free survival (PFS) (median PFS=1.6 vs. 8.8 months, p<0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT expression remained a significant independent poor prognostic factor for OS (hazard ratio (HR)=7.0; 95% confidence interval (CI)=3.0-16.6; p<0.001) and PFS (HR=6.8; 95% CI=3.0-15.2; p<0.001). Conclusion: PTCL patients with high p-AKT expression showed aggressive clinical courses with significantly worse OS and PFS and a poor chemotherapy response rate. We suggest that targeting the PI3K/AKT pathway may be a promising therapeutic strategy for PTCL.
    Anticancer research 04/2015; 35(4):2465-74. · 1.83 Impact Factor
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    ABSTRACT: The risk factors for venous thromboembolism (VTE) in diffuse large B-cell lymphoma (DLBCL) are not clear although thrombosis can be associated with host status, tumor burden and inflammatory activity. We assessed the effect of those factors on VTE in a cross-sectional study of patients enrolled in a prospective cohort study. We analyzed the occurrence of VTE in 322 patients with newly diagnosed DLBCL who received R-CHOP (rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone) between 2008 and 2011. Serum levels of inflammatory cytokines were measured from serum samples archived at diagnosis. With a median follow-up duration of 41.9 months, VTE was documented in 34 patients (10.6%). A comparison of baseline characteristics indicated the group with VTE had higher percentage of old age, stage III/IV and extranodal involvements than the group without VTE (P < 0.05). Thus, the International Prognostic Index was significantly associated with VTE, but the Khorana score was not. A univariate competing risk factor analysis for VTE revealed that increased levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 were also associated with VTE (P < 0.05) in addition to host and tumor burden. However, a multivariate analysis showed that two host factors including age ( 60 years) and poor performance were independent risk factors for VTE. s Among potential risk factors for VTE including tumor burden and inflammatory activity, age and performance status had a strong impact on the occurrence of VTE in patients with DLBCL who received R-CHOP.
    Cancer Research and Treatment 03/2015; DOI:10.4143/crt.2014.266 · 3.32 Impact Factor
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    ABSTRACT: Viral oncogenes and host immunosenescence have been suggested as causes of Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV + DLBCL) of the elderly. To investigate the molecular genetic basis of immune evasion and tumor outgrowth, we analyzed copy number alterations (CNAs) and gene expression profiles in EBV + DLBCL samples compared with EBV - DLBCL. There were relatively few genomic alterations in EBV + DLBCL compared with those detected in EBV-negative DLBCL. The most frequent CNAs (>30%) in EBV + DLBCLs were gains at 1q23.2-23.3, 1q23.3, 1q32.1, 5p15.3, 8q22.3, 8q24.1-24.2, and 9p24.1; losses at 6q27, 7q11.2, and 7q36.2-36.3 were also recurrent. A gene expression profile analysis identified the host immune response as a key molecular signature in EBV + DLBCL. Antiviral response genes, proinflammatory cytokines, and chemokines associated with the innate immune response were overexpressed, indicating the presence of a virusinduced inflammatory microenvironment. Genes associated with the B-cell receptor signaling pathway were downregulated. An integrated analysis indicated that SLAMF1 and PDL2 were key targets of the gains detected at 1q23.2-23.3 and 9p24.1. The chromosomal gain at 9p24.1 was associated with poor overall survival. Taken together, our results led to the identification of recurrent copy number alterations and distinct gene expression associated with the host immune response in EBV + DLBCL. We suggest that the upregulation of PDL2 on 9p24.1 promotes immune evasion and is associated with poor prognosis in EBV + DLBCL. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 03/2015; 54(6). DOI:10.1002/gcc.22249 · 4.04 Impact Factor
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    ABSTRACT: Clinical features and treatment outcomes of primary cutaneous B-cell lymphoma (PCBCL) have rarely been reviewed, due to the rarity and pathologic obscurity of this disease. We reviewed 21 patients who were pathologically diagnosed with PCBCL from Samsung Medical Center's lymphoma cohort, following the WHO-EORTC classification system: primary cutaneous follicle-center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT), and cutaneous diffuse large B-cell lymphoma, other (PCDLBCL, other). Of 2831 B-cell lymphoma cases, PCBCL comprised only 0.74 % of cases (N = 21, eight PCLBCL, LT (0.28 %), 10 PCMZL (0.35 %), two PCDLBCL, other (0.06 %), and one PCFCL (0.03 %)). Eighteen of 21 patients received treatment for PCBCL (12 chemotherapy alone, three radiotherapy alone, three chemotherapy following radiotherapy) and complete response (CR) was observed in 17 patients. The median progression-free survival was 44 months [95 % confidence interval (CI): 11-61 months]. Two patients had died at the time of analysis, with a median follow-up duration of 85 months [95 % confidence interval (CI): 55-118 months]. PCBCL cases in this study have a higher proportion of disseminated PCMZL and PCLBCL, LT, and excellent outcomes were observed with chemotherapy, including R-CHOP or R-CVP irrespective of staging and pathologic subtype.
    International Journal of Hematology 03/2015; 101(3). DOI:10.1007/s12185-014-1728-2 · 1.92 Impact Factor
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    ABSTRACT: Assessment of tumour viability after treatment is essential for prediction of treatment failure in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We aimed to assess the use of the post-treatment Deauville score on PET-CT and Epstein-Barr virus DNA as a predictor of residual tumour, to establish the risk of treatment failure in patients with newly diagnosed ENKTL.
    02/2015; 2(2). DOI:10.1016/S2352-3026(15)00002-2
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    ABSTRACT: - Copyright © 2014, Ferrata Storti Foundation.
    Haematologica 12/2014; 100(3). DOI:10.3324/haematol.2014.116087 · 5.81 Impact Factor
  • Seung Eun Lee · So Young Kang · Kengo Takeuchi · Young Hyeh Ko
    Hematological Oncology 12/2014; 32(4). DOI:10.1002/hon.2125 · 3.08 Impact Factor
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    Mineui Hong · Won Seog Kim · Young Hyeh Ko
    The Korean Journal of Pathology 12/2014; 48(6):430-3. DOI:10.4132/KoreanJPathol.2014.48.6.430 · 0.17 Impact Factor
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    ABSTRACT: Background Salivary duct carcinoma (SDC) is a highly aggressive subtype of salivary gland cancers and there is no established standard therapy for this disease. Thus, development of molecular markers for SDC will be important to guide the diagnosis and therapy of this aggressive tumor.Methods We performed next-generation sequencing using the Ion Torrent AmpliSeq cancer panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes, and we analyzed copy number variations (CNVs) of 21 genes by NanoString nCounter for 37 patients with SDC. Fluorescent in situ hybridization was also conducted to confirm ERBB2 gene amplification. Clinical records and tumor histopathology of the patients were retrospectively reviewed.ResultsGenetic alterations were detected in 29 of 37 (78.3%) tumors, including mutations in PIK3CA (N¿=¿9, 24.3%), ERBB2 (N¿=¿4, 10.8%), and EGFR (N¿=¿4, 10.8%). To our knowledge, this is the first time that ERBB2 mutations have been reported in this tumor type. Both PIK3CA and ERBB2 mutation status were associated with poor overall survival, but without statistical significance. ERBB2 amplification was strong and common in SDC and almost all cases also exhibited EGFR and ERBB3 amplifications.Conclusions This study reports the largest and most comprehensive analysis of DNA aberrations in SDC. Our results show that PIK3CA and/or ERBB2 alterations in the development of SDC might be a useful diagnostic tool and could serve as a potential therapeutic target.
    Journal of Translational Medicine 10/2014; 12(1):299. DOI:10.1186/s12967-014-0299-6 · 3.93 Impact Factor
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    ABSTRACT: Background: The simultaneous presentation of systemic diffuse large B cell lymphoma (DLBCL) with central nervous system (CNS) disease is not well controlled by either R-CHOP or systemic methotrexate (MTX) alone. Methods: We conducted a pilot trial with 6 patients who were initially diagnosed with systemic DLBCL with CNS involvement. Patients were treated with a systemic MTX plus R-CHOP regimen. Results: The overall response rate was 4/6 (66.7%). The CNS response rate and systemic response rate were 4/6 (66.7%) and 5/6 (83.3%), respectively. The median response duration of the 4 patients with complete remission at completion was 25.5 months, and the median survival of all patients was 25.1 months. CNS lesions progressed in all relapsed and refractory patients, while systemic disease progression was observed in 1 patient. No fatal hematologic adverse effects, hepatotoxicity or nephrotoxicity were observed. Conclusions: The dose of systemic MTX (1∼1.5 g/m(2)) or dose intensity (4-week interval in 4 patients) used in this trial was considered insufficient. Therefore, the dose of MTX or interval of each chemotherapy cycle should be modified in future trials to control CNS disease involved with DLBCL.
    Acta Haematologica 10/2014; 133(2):179-182. DOI:10.1159/000362149 · 1.12 Impact Factor

Publication Stats

1k Citations
392.60 Total Impact Points


  • 2002–2015
    • Sungkyunkwan University
      • • School of Medicine
      • • Department of Pathology
      • • Department of Radiology
      Sŏul, Seoul, South Korea
  • 1998–2015
    • Samsung Medical Center
      • Department of Pathology
      Sŏul, Seoul, South Korea
  • 2009
    • Gyeongsang National University
      Shinshū, Gyeongsangnam-do, South Korea
  • 2001
    • Western Diagnostic Pathology
      Perth City, Western Australia, Australia
  • 1993
    • Hanyang University
      • College of Medicine
      Ansan, Gyeonggi, South Korea