Neonatal Morbidities Associated with Histologic Chorioamnionitis Defined Based on the Site and Extent of Inflammation in Very Low Birth Weight Infants

Kim, Su Yeong,Choi, Chang Won,Jung, Euiseok,Lee, Juyoung,Lee, Jin A,Kim, Haeryoung,Kim, Ee-Kyung,Kim, Han-Suk,Kim, Beyong Il,Choi, Jung-Hwan The Korean Academy of Medical Sciences 2015 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.30 No.10

Expression Profiles of Epithelial-Mesenchymal Transition-Associated Proteins in Epithelial Ovarian Carcinoma

Kim, Mi-Kyung,Kim, Min A,Kim, Haeryoung,Kim, Yong-Beom,Song, Yong-Sang Hindawi Publishing Corporation 2014 BioMed research international Vol.2014 No.-

<P>Epithelial-mesenchymal transition (EMT) has been suggested to contribute to tumor progression and acquisition of therapeutic resistance. To assess the clinical significance of EMT-associated proteins, we evaluated the expression of Snail and Slug, the key regulators of EMT, in the primary ovarian cancer samples (<I>n</I> = 103) by immunohistochemistry. Snail was differentially expressed according to the histologic subtype (<I>P</I> = 0.001) and was predominantly expressed in serous and endometrioid types. In the serous and endometrioid adenocarcinomas, the expression of Snail remained high across the stage and grade, suggesting its role in the early phase of carcinogenesis. However, the expression of Snail and Slug was not related to chemoresistance and poor prognosis and did not serve as independent predictive or prognostic marker.</P>

Tumour Epithelial and Stromal Characteristics of Hepatocellular Carcinomas with Abundant Fibrous Stroma: Fibrolamellar versus Scirrhous Hepatocellular Carcinoma

( Haeryoung Kim ),( Young-joo Kim ),( Hyungjin Rhee ),( Jeong Eun Yoo ),( Venancio A. F. Alves ),( Gi Jeong Kim ),( Hye Min Kim ),( Paulo Herman ),( Aline Chagas ),( Young Nyun Park ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterised by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. Methods: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for K7, K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67. Results: FL-HCC patients were younger than S-HCC patients (p<0.001), and chronic liver disease was seen in the background of 88.2% of S-HCC and in none of the FL-HCC. CD68 and CD163-positive tumour-infiltrating macrophages and FAP-positive cancer-associated fibroblasts (CAFs) were more abundant in the stroma of S-HCCs compared to FL-HCCs (p<0.05, all). Tumour epithelial K19 expression was more frequent in S-HCCs compared to FL-HCCs (p=0.023). Significant positive correlations were seen between pSTAT3 expression status in tumour epithelial cells and CAFs, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, EpCAM, CD56/NCAM, CCN2 expression and Ki-67 labelling index between S-HCCs and FL-HCCs. Conclusions: S-HCC and FL-HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL-HCC is composed of dense lamellated collage nous bands with sparse cellular components, S-HCC demonstrates more abundant CAF and tumour-infiltrating macrophages, and stemness- related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of these tumours.

Association of overexpression of hexokinase II with chemoresistance in epithelial ovarian cancer.

Suh, Dong Hoon,Kim, Min A,Kim, Haeryoung,Kim, Mi-Kyung,Kim, Hee Seung,Chung, Hyun Hoon,Kim, Yong-Beom,Song, Yong Sang Springer-Verlag Italia 2014 Clinical and experimental medicine Vol.14 No.3

<P>This aim of this study was to evaluate the relationship between hexokinase II expression and chemoresistance in epithelial ovarian cancer. One hundred and eleven paraffin-embedded specimens from patients with epithelial ovarian cancer were immunohistochemically stained for hexokinase II. Subsequently, the association between hexokinase II overexpression and clinicopathologic characteristics including chemoresistance was assessed. Survival analyses were also performed for evaluating the prognostic value of hexokinase II overexpression. Tumor recurrence within 6 months after termination of first-line chemotherapy was considered to indicate chemoresistance. Hexokinase II overexpression was associated with chemoresistance (p = 0.029) and was an independent risk factor for chemoresistance [odds ratio (OR) 3.37; 95 % confidence interval (CI) 1.07-10.62; p = 0.038] along with non-optimal debulking surgery (OR 4.93; 95 % CI 1.43-16.98; p = 0.011). Hexokinase II overexpression was significantly associated with decreased progression-free survival (p = 0.002) and showed a similar trend for overall survival (p = 0.101). Cox regression analysis revealed that hexokinase II overexpression was an independent prognostic factor for early recurrence (hazard ratio 2.63; 95 % CI 1.40-4.92; p = 0.002). Our findings suggest that hexokinase II overexpression is associated with short progression-free survival, which could be associated with chemoresistance in epithelial ovarian cancer.</P>

Overexpression of hexokinase II as a poor prognostic marker for recurrence in epithelial ovarian cancer

( Dong Hoon Suh ),( Min A Kim ),( Haeryoung Kim ),( Mi Kyung Kim ),( Hee Seung Kim ),( Hyun Hoon Chung ),( Yong Beom Kim ),( Yong Sang Song ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.98 No.-

Overexpression of hexokinase (HK) II in many cancer cells is thought to provide cancer cells with an anti-apoptotic feature. This study aimed to evaluate the prognostic values of the HK II overexpression in relation to the chemoresistance in epithelial ovarian cancer (EOC). One hundred eleven paraffin embedded specimens from patients with EOC were immunohistochemically stained for HK II protein. Staining patterns were analyzed according to clinicopathologic characteristics including chemoresistance, defined as tumor recurrence <6 months after last chemotherapy. Overexpression of HK II was detected in 48.2% of all patients. Cytoplasmic and nuclear expressions of HK II were observed in 83 (75.5%) and 34 (30.9%), respectively. At a median follow-up of 39 months (range 0-94 months), tumor recurred in 55 (49.5%) and 29 (26.1%) were chemoresistant. HK II overexpression was significantly associated with chemoresistance and recurrence (p=0.029 and p=0.022, respectively), however, advanced stage with a marginal significance (p=0.055). Advanced stage (odds ratio [OR] 6.83; 95% confidence interval [CI] 1.14-41.07; p=0.036) and non-optimal debulking (OR 4.61; 95% CI 1.30-16.30; p=0.018), but not HK II overexpression (OR 2.79, 95% CI 0.88-8.81; p=0.082), were the independent risk factors for chemoresistance. Nevertheless, progression-free survival (PFS) was shorter for patients with HK II overexpression than those without overexpression (p=0.030). Cox proportional hazard regression analysis revealed that HK II overexpression was the independent prognostic factor for recurrence (hazard ratio [HR] 3.30; 95% CI 1.78-6.10; p=0.014). Nuclear expression of HK II was observed significantly more in advanced stage tumor than early stage tumor (p=0.044). Our findings suggest that overexpression of HK II might be a useful prognostic marker for predicting recurrence, but not chemoresistance, in patients with EOC.

A Feasibility Study of Adenosine Triphosphate-based Chemotherapy Response Assay (ATP-CRA) as a Chemosensitivity Test for Lung Cancer

Shin Myung Kang,Moo Suk Park,Joon Chang,Haeryoung Kim,Dong-Hwan Shin,Se Kyu Kim,Kyung Young Chung,Dae Joon Kim,Joo Hyuk Sohn,최성호,Jeongmi Kim,Eun Jin Yoon,Joo-Hang Kim 대한암학회 2005 Cancer Research and Treatment Vol.37 No.4

Purpose: A chemosensitivity test can reflect the differences in responses of individual cancer patients to chemotherapeutic agents. The adenosine triphosphatebasedchemotherapy response assay (ATP-CRA)is an accurate method, which does not require a large amount of tissue specimen. So far, no studies have evaluated the utility of the ATP-CRA in Korea. Therefore, we investigated the clinical usefulness of the ATP-CRA in 53 patients with lung cancer.Materials and Methods: Tumor tissues were obtained from bronchoscopic biopsies or surgical resections. The validity of ATP-CRA was assessed focusing on the success rate, experimental error level (intraassay mean coefficient of variation [CV]) and reproducibility.Results: The overall success rate of ATP-CRA was 90.6% (48/53). Normal cells were effectively eliminated from the tumor tissues with the use of ficoll gradient centrifugation and immunomagnetic separation, which was confirmed using loss of heterozygosity analysis of the 3p deletion. The mean CV of ATP assays was 10.5± 4.6%. The reproducibility of ATP assays was 94±3.8%. The results of the ATP assays were reported to physicians within 7 days of specimen collection. More than 6 anticancer drugs were tested on the tumor specimens obtained from bronchoscopic biopsies.Conclusion: The ATP-CRA is a stable, accurate and potentially practical chemosensitivity test in patients with lung cancer.

HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c‐myc during tumor formation

Kim, Se‐,Heon,Koo, Bon‐,Seok,Kang, Suki,Park, Kyeongmee,Kim, Haeryoung,Lee, Kyung Ryul,Lee, Moo Joo,Kim, Jong Man,Choi, Eun Chang,Cho, Nam Hoon Wiley Subscription Services, Inc., A Wiley Company 2007 International journal of cancer: Journal internati Vol.120 No.7

<P><B>Abstract</B></P><P>The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV‐related molecules between TC and tonsillitis (CFT), p16, survivin, HIF‐1α, skp‐1, cyclin A, cyclin B1, c‐myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% <I>vs.</I> 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV‐negative TC, HPV‐positive TC showed a strong association with p16 overexpression (<I>p</I> < 0.0001), and an inverse association with EGFR amplification (<I>p</I> = 0.0478). HPV‐16 integration status was strongly associated with c‐myc amplification (<I>p</I> = 0.034) and HIF‐1α overexpression (<I>p</I> = 0.022). HPV‐16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1‐S phase. © 2006 Wiley‐Liss, Inc.</P>

Update on pancreatic cystic fluid analysis

Haeryoung Kim 한국간담췌외과학회 2015 한국간담췌외과학회 학술대회지 Vol.2015 No.9

Human hepatocellular carcinomas with “Stemness”‐related marker expression: keratin 19 expression and a poor prognosis

Kim, Haeryoung,Choi, Gi Hong,Na, Deuk Chae,Ahn, Ei Young,Kim, Gwang Il,Lee, Jae Eun,Cho, Jai Young,Yoo, Jeong Eun,Choi, Jin Sub,Park, Young Nyun Wiley Subscription Services, Inc., A Wiley Company 2011 Hepatology Vol.54 No.5

<P><B>Abstract</B></P><P>There is a recently proposed subtype of hepatocellular carcinoma (HCC) that is histologically similar to usual HCC, but characterized by the expression of “stemness”‐related markers. A large‐scale study on two different cohorts of HCCs was performed to investigate the clinicopathologic features and epithelial‐mesenchymal transition (EMT)‐related protein expression status of this subtype of HCCs. The expression status of stemness‐related (e.g., keratin 19 [K19], cluster of differentiation [CD]133, epithelial cell adhesion molecule [EpCAM], and c‐kit) and EMT‐related markers (e.g., snail, S100A4, urokinase plasminogen activator receptor [uPAR], ezrin, vimentin, E‐cadherin, and matrix metalloproteinase [MMP]2) were examined using tissue microarrays from cohort 1 HCCs (n = 137). K19 protein expression in cohort 2 HCCs (n = 237) was correlated with the clinicopathologic parameters and messenger RNA (mRNA) levels of K19, uPAR, VIL2, Snail, Slug, and Twist. K19, EpCAM, c‐kit, and CD133 positivity were observed in 18.2%, 35.0%, 34.3%, and 24.8%, respectively. K19 was most frequently expressed in combination with at least one other stemness‐related marker (92.0%). K19‐positive HCCs demonstrated more frequent major vessel invasion and increased tumor size, compared to K19‐negative HCCs (<I>P</I> < 0.05). K19 was most significantly associated with EMT‐related protein expression (e.g., vimentin, S100A4, uPAR, and ezrin) (<I>P</I> < 0.05) and a poor prognosis (overall survival: <I>P</I> = 0.018; disease‐free survival: <I>P</I> = 0.007) in cohort 1. In cohort 2, HCCs with high K19 mRNA levels demonstrated higher mRNA levels of Snail, uPAR, and MMP2 (<I>P</I> < 0.05). K19‐positive HCCs demonstrated more frequent microvascular invasion, fibrous stroma, and less tumor‐capsule formation, compared to K19‐negative HCCs (<I>P</I> < 0.05). K19 expression was a significant independent predictive factor of poor disease‐free survival (<I>P</I> = 0.032). <I>Conclusion:</I> K19 was well correlated with clinicopathologic features of tumor aggressiveness, compared to other stemness‐related proteins. K19‐positive HCCs showed significantly increased EMT‐related protein and mRNA expression, suggesting that they may acquire more invasive characteristics, compared to K19‐negative HCCs through the up‐regulation of EMT‐associated genes. (H<SMALL>EPATOLOGY</SMALL> 2011;)</P>

Combined Hepatocellular-Cholangiocarcinoma: Changes in the 2019 World Health Organization Histological Classification System and Potential Impact on Imaging-Based Diagnosis

Kim Tae-Hyung,Kim Haeryoung,Joo Ijin,Lee Jeong Min 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.10

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver cancer (PLC) with both hepatocytic and cholangiocytic phenotypes. Recently, the World Health Organization (WHO) updated its histological classification system for cHCC-CCA. Compared to the previous WHO histological classification system, the new version no longer recognizes subtypes of cHCC-CCA with stem cell features. Furthermore, some of these cHCC-CCA subtypes with stem cell features have been recategorized as either hepatocellular carcinomas (HCCs) or intrahepatic cholangiocarcinomas (ICCs). Additionally, distinctive diagnostic terms for intermediate cell carcinomas and cholangiolocarcinomas (previous cholangiolocellular carcinoma subtype) are now recommended. It is important for radiologists to understand these changes because of its potential impact on the imagingbased diagnosis of HCC, particularly because cHCC-CCAs frequently manifest as HCC mimickers, ICC mimickers, or as indeterminate on imaging studies. Therefore, in this review, we introduce the 2019 WHO classification system for cHCC-CCA, illustrate important imaging features characteristic of its subtypes, discuss the impact on imaging-based diagnosis of HCC, and address other important considerations.