Journal of Pathology and Translational Medicine

Woon Sup Han

31 Articles

Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer.: Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung; Korean J Pathol. 2011;45(1):53-61.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.53

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BACKGROUND
Triple negative breast cancer (TNBC) is defined as a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. Many TNBCs show a profound infiltration of tumor infiltrating lymphocytes (TILs). It is still uncertain whether these TILs are protumoral or antitumoral. Regulatory T cells (Tregs) play a role in inducing immune tolerance to antigens, and they may be selectively recruited by cancer cells. This study was conducted to evaluate the significance of TILs with an emphasis on forkhead box p3 (Foxp3), which is a marker for CD25+CD4+ Treg in TNBC.
METHODS
We investigated the Foxp3, CD8 and CD4 expressions in 100 cases of TNBC by immunohistochemistry and using a tissue microarray. The Foxp3 expression was divided as the high and low infiltration groups (cut-off value=20).
RESULTS
The high infiltration group was correlated with higher histologic and nuclear grades. However, Foxp3+ Tregs were decreased in the T3 and T4 TNBCs as compared to that of the T1 and T2 TNBCs. No significant differences were found for the nodal status, lymphovascular invasion, stage, recurrence and overall survival.
CONCLUSIONS
High Foxp3+ Treg infiltration in TNBC is correlated with the nuclear and histologic grades, but there was no relation to recurrence and overall survival.

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Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer
In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee
Cancer Research and Treatment.2017; 49(2): 399. CrossRef
Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer
Sewha Kim, Anbok Lee, Woosung Lim, Sanghui Park, Min Sun Cho, Heasoo Koo, Byung-In Moon, Sun Hee Sung
Journal of Breast Cancer.2014; 17(1): 8. CrossRef

Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics.: Harin Cheong, Hanna Kang, Hyung Kyung Kim, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo; Korean J Pathol. 2010;44(3):243-251.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.243

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Abstract PDF

BACKGROUND
This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size < or = 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm).
METHODS
We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining.
RESULTS
Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression. There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions.
CONCLUSIONS
Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.

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Freeze-dried bovine amniotic membrane as a cell delivery scaffold in a porcine model of radiation-induced chronic wounds
Daemyung Oh, Daegu Son, Jinhee Kim, Sun-Young Kwon
Archives of Plastic Surgery.2021; 48(4): 448. CrossRef
Polydeoxyribonucleotide Improves Peripheral Tissue Oxygenation and Accelerates Angiogenesis in Diabetic Foot Ulcers
Seoyoung Kim, Junhyung Kim, Jaehoon Choi, Woonhyeok Jeong, Sunyoung Kwon
Archives of Plastic Surgery.2017; 44(06): 482. CrossRef

Frequency of Intrahepatic FoxP3+ Regulatory T cells during the Natural Course of Chronic Hepatitis B: An Immunohistochemical Study Using Needle-Biopsied Liver Tissue.: Ji Yoon Bae, Hyung Kyung Kim, Hanna Kang, Ha Rin Cheong, Dong Eun Song, Sun Hee Sung, Heasoo Koo, Woon Sup Han, Jeong Kyong Lee, Tae Hun Kim, Kyu Won Chung, Min Sun Cho; Korean J Pathol. 2010;44(2):132-140.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.132

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Abstract PDF

BACKGROUND
Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized.
METHODS
Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry.
RESULTS
The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load.
CONCLUSIONS
FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.

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Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer
Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung
The Korean Journal of Pathology.2011; 45(1): 53. CrossRef

Histopathological Evaluation of Pediatric Intestinal Pseudo-Obstruction: Quantitative Morphometric Analysis of Pathological Changes in the Enteric Nervous System.: Hyung Kyung Kim, Harin Cheong, Hanna Kang, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo; Korean J Pathol. 2010;44(2):162-172.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.162

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Abstract PDF

BACKGROUND
This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis.
METHODS
We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC).
RESULTS
Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group.
CONCLUSIONS
Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.

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Histomorphology of enteric neurons and enteric ganglia in different layers of human fetal colon
Chacchu Bhattarai, Phanindra P. Poudel, Arnab Ghosh, Sneha G. Kalthur
Journal of Taibah University Medical Sciences.2022; 17(4): 556. CrossRef
Diagnostic utility of Bcl-2 immunohistochemical expression in pediatric functional bowel obstruction cases with ganglionated specimens
Lobna Abd El Fattah Mohamed, Nedal Ahmed Hegazy, Faten Abd El Aziz Ghazal, Ahmed Mohy El Din Zaki, Ahmed Bassiouny Radwan, Sarah Adel Hakim
Annals of Pediatric Surgery.2022;[Epub] CrossRef
PTEN Immunohistochemistry
Simone Antunes Terra, Pedro Luiz Toledo de Arruda Lourenção,, Maria Aparecida Marchesan Rodrigues
Archives of Pathology & Laboratory Medicine.2022; 147(5): 577. CrossRef
Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells
Simone Antunes Terra, Anderson Cesar Gonçalves, Pedro Luiz Toledo de Arruda Lourenção, Maria Aparecida Marchesan Rodrigues
World Journal of Gastroenterology.2021; 27(44): 7649. CrossRef
Morphometric profile of large intestinal neuronal plexuses in normal perinatal autopsies and Hirschsprung disease
H. Subramanian, B. A. Badhe, P. C. Toi, K. Sambandan
Neurogastroenterology & Motility.2017;[Epub] CrossRef

Metaplastic Squamous Carcinoma of the Breast: Clinicopathologic Analysis of 17 Cases.: Sun Ah Lee, Kyung Eun Lee, Byung In Moon, Woon Sup Han, Sun Hee Sung; Korean J Pathol. 2009;43(1):20-25.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.20

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Abstract PDF

BACKGROUND
Squamous cell carcinoma of the breast is very rare and it is considered to arise from metaplastic change of ductal carcinoma. Metaplastic squamous cell carcinoma (MSC) of the breast includes pure squamous cell carcinoma, metaplastic adenosquamous carcinoma and low grade adenosquamous carcinoma. Most of the cases of MSC of the breast were reported to have lymph node metastasis and this has a worse prognosis than that of conventional invasive ductal carcinoma.
METHODS
We collected 17 cases of MSC of the breast from 1,173 cases of breast cancer and analyzed the clinicopathological characteristics.
RESULTS
The age range was 31 to 69 years (mean age: 47.2). The mean tumor size was 3.6 cm. Twelve cases (70.6%) had a negative nodal status. The majority of the cases were of a high nuclear grade (grade III: 76.5%), and a high histologic grade (grade III: 88.2%). All the cases had no amplification of HER2, and they were negative for hormonal receptors, except for 2 cases with weak positivity. All the cases showed positivity for EGFR (3+: 14 cases, 1+: 3 cases). Clinical relapse was found in 3 patients on follow up and two of them expired due to lung and bone metastasis.
CONCLUSIONS
MSC is associated with high nuclear and histologic grades, a high EGFR expression and they are triple negative for ER, PR, and HER2. The EGFR immunopositivity of MSC suggests a basal-like subtype.

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Eccrine ductal and acrosyringeal metaplasia in breast carcinomas: report of eight cases
Tibor Tot
Virchows Archiv.2019; 474(3): 383. CrossRef
Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer
Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung
The Korean Journal of Pathology.2011; 45(1): 53. CrossRef

ISUP/WHO Classification of Papillary Urothelial Neoplasms of Urinary Bladder: Consensus Study Conducted by Korean Society of Urogenital Pathology.: Jung Weon Shim, Jae Y Ro, Nam Hoon Cho, Young Sik Kim, Yong Wook Park, Sang In Shim, Dong Wha Lee, Yeong Jin Choi, Woon Sup Han; Korean J Pathol. 2006;40(4):282-288.

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Abstract PDF: BACKGROUND
Pathologic grading, one of the most important prognostic factors of papillary urothelial neoplasia (PUN) of the urinary bladder, has been revised continuously. The current study focused on the analysis of interobserver agreement on PUN of the urinary bladder bet- ween 1973 WHO classification (WHO 1973) and 1998 WHO/ISUP classification.
METHODS
Seventy five cases from 15 institutions were collected, and after review by Korean Society of Urogenital Pathology (KSUP), 30 cases were selected as follows; group I, WHO grade 1 and papillary urothelial neoplasm of low malignant potential by ISUP (7 cases), group II, WHO grade 2 and low-grade papillary urothelial carcinoma (16 cases), and group III, WHO grade 3 and high-grade papillary urothelial carcinoma (7 cases). Seventy five general surgical pathologists who participated in this study were asked to grade the tumors based on WHO/ISUP classification. Interobserver agreement between the participants' diagnosis and KSUP consensus diagnosis was analyzed by kappa value.
RESULTS
Interobserver agreement assessed by kappa value for all diagnostic groups was very low; for group I, kappa value was -0.900893722; for group II, -0.944650025, and for group III, -0.876728996. The overall kappa value of pathology residents was better than that of practicing pathologists.
CONCLUSIONS
The 1998 WHO/ ISUP classification could not be easily translated from the 1973 WHO classification and because of poor interobserver agreement, it appears that further work would be needed before it can be practically applied.

Loss of PTEN Expression in Breast Cancers.: Sun Hee Chang, Shi Nae Lee, Min Sun Cho, Heasoo Koo, Woon Sup Han, Seock Ah Im, Byung In Moon, Hyun Suk Suh, Hye Young Choi, Sun Hee Sung; Korean J Pathol. 2005;39(4):236-241.

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Abstract PDF: Background
: PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression.
Results
: Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.

RUNX3 Methylation Status in Colonic Carcinoma and Adenoma.: Shi Nae Lee, Min Sun Cho, Woon Sup Han; Korean J Pathol. 2004;38(1):42-45.

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Abstract PDF: BACKGROUND
RUNX3 is expressed throughout the luminal gastrointestinal tract. RUNX3 is on chromosome 1p36, a location considered to carry an important tumor suppressor for many types of cancers. Epigenetic silencing of RUNX3 is causally related to human gastric cancer.
METHODS
Colorectal cancers, adenoma, and the corresponding normal mucosa were obtained from 26 individual patients. To identify methylation of RUNX3 in colonic carcinogenesis, methylation-specific PCR was performed.
RESULTS
RUNX3 methylation was found in one case of colonic carcinoma. The normal mucosa and tubular adenoma of this case had no methylation. No other cases were found to have methylations.
CONCLUSIONS
These results are very different from the findings of gastric carcinomas, where frequent DNA methylation in the vicinity of the RUNX3 promoter is found. Although, the possibility of a role of RUNX3 methylation in the colon can not be completely ruled out, these results suggest that methylation of the RUNX3 promoter region might not contribute to the adenoma-carcinoma sequence of the colon.

Comparison of Ziehl-Neelsen Stain and TB-PCR on Detection of Mycobacterium tuberculosisin Formalin-fixed, Paraffin-embedded Tissues of Chronic Granulomatous Inflammation.: Min Sun Cho, Shi Nae Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2003;37(6):379-383.

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Abstract PDF: BACKGROUND
TB-PCR is a faster and more sensitive method to detect mycobacterium than acid-fast bacilli (AFB) stain, which is laborious and time consuming. We compared the sensitivity and specificity of AFB stain and TB-PCR and examined the possibility of TB-PCR as a confirmative test without AFB stain in the diagnosis of tuberculosis.
METHODS
We performed Ziehl-Neelsen stain and nested PCR using a commercially available TB-PCR kit amplifying IS6110 sequence in 81 cases of paraffin-embedded tissues diagnosed as chronic granulomatous inflammation. In addition, we evaluated the morphology of granuloma and the presence of caseation necrosis.
RESULTS
Of the 81 cases studied, 22 (27.2%) and 40 (49.4%) were positive for AFB stain and TB-PCR, respectively. Of 49 cases accompanying caseation necrosis, 19 (38.8%) were AFB stain positive and 37 (75.5%) were TB-PCR positive; a result that is comparable with that of other reports. Of the 22 AFB-positive cases, 2 were TB-PCR negative.
CONCLUSION
TB-PCR is very helpful for the diagnosis of tuberculosis in routinely processed, formalin-fixed, paraffin-embedded tissue samples. Nevertheless, AFB stain should continue to be performed at the same time.

Effects of Calcitriol on Delayed Neuronal Damage of Hippocampus in Transient Global Ischemia Model of Mature Gerbil.: Hye Jin Park, Hea Soo Koo, Woon Sup Han, Kyung Kyu Choi; Korean J Pathol. 2003;37(5):307-315.

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Abstract PDF: BACKGROUND
It is well documented that calcium ions perform a major role in neuronal degeneration in cerebrovascular disease and the other degenerative diseases, and that 1,25-dihydroxyvitamin D3 (D3) has the dose-dependent protective effects. This study was performed to examine the effects of different D3 dosages against delayed neuronal damage of the hippocampus.
METHODS
Mature mongolian gerbils were injected with either 0.8 microgram/kg/day (group 2) for 5 days or 1.0 microgram/kg/day for 8 days (group 3) prior to the 10 min ligation of the bilateral common carotid arteries. Immunohistochemical expression for the glial cell line-derived neurotrophic factor (GDNF), the basic fibroblast growth factor (bFGF) and the platelet-derived neurotrophic factor (PDNF) was observed in the D3-injected (0.8 microgram/kg/day for 5 days) group.
RESULTS
Group 2 showed a highly significant attenuation of delayed neuronal damage in the lateral CA1 region at 7 days after reperfusion. Group 3 showed unilateral or bilateral hemispheric infarcts 24 h after the onset of reperfusion. The D3-injected group showed a markedly increased bFGF expression level.
CONCLUSION
The dose-dependent effect of D3 suggests the importance of determining the appropriate D3 dose for clinical applications. Although the mechanism(s) of neuroprotection by D3 remains unclear, D3 may facilitate a reduction in ischemia-induced oxidative stress via the activation of the neurotrophic factors, including bFGF and GDNF.

KAI-1 Protein Expression in Breast Cancer: Correlation with Axillary Lymph Node Metastasis and other Prognostic Factors.: Shi Nae Lee, Min Sun Cho, Sun Hee Sung, Hea soo Koo, Ok Kyung Kim, Woon Sup Han; Korean J Pathol. 2003;37(4):239-245.

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Abstract PDF: BACKGROUND
KAI-1 is a metastasis suppressor gene. We have evaluated the correlationbetween KAI-1 protein expression in ductal carcinomas of the breast and axillary lymph nodemetastasis.
METHODS
The expression of KAI-1 protein was confirmed by immunohistochemistryto examine breast tissues of ductal carcinomas from 50 patients with nodal metastasisand from 53 patients without metastasis. Western blot analysis was performed on fresh frozenbreast tissues from 17 cases with nodal metastasis and from 19 cases without metastasis.
RESULTS
Immunohistochemical KAI-1 protein expression was decreased or negative in 39out of 50 cases with metastasis (78%), compared with 8 out of 53 cases with no metastasis(15.1%). The difference was statistically significant (p<0.05). Immunohistochemical KAI-1protein expression was significantly decreased in cases with higher modified Black's nucleargrade (p=0.027) and larger tumor size (p=0.039). Western blot analysis showed positivebands at 29.5 kDa in 8 out of 19 cases without metastasis (42.1%), and none of the 17 caseswith metastasis showed positive bands (p=0.0024).
CONCLUSION
These results suggest thepossibility that KAl-1 might play a major role of a metastasis suppressor gene in addition tothe part it plays in the growth and progression of human breast ductal carcinoma. In addition, the decreased expression of KAI-1 protein in breast ductal carcinomas could be used as afactor suggesting poor prognosis.

Suprasellar Endodermal Sinus Tumor Presenting with Tonic-Clonic Seizure: An Autopsy Case Report.: Min Jin Lee, Hea Soo Koo, Woon Sup Han, Sun Hee Sung, Yong Jae Kim, Hye Young Choi; Korean J Pathol. 2002;36(6):433-439.

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Abstract PDF: We report the clinical course and autopsy findings of a 19-year-old girl with endodermal sinus tumor involving the thalamus, hypothalamus, and basal ganglia. The patient initially had tonic-clonic seizures with abnormal signal involving the right hippocampus, amygdala, basal ganglia, putamen, and dentate gyrus. The signal intensity of the posterior pituitary on T1-weighted images was decreased at the time of admission, which was not associated with clinical symptoms of diabetes insipidus (DI). A huge tumor mass as well as central DI developed within 10 months. The postmortem examination showed gliosis with calcification involving the right basal ganglia, internal capsule, and white matter, in addition to a tumor mass involving the thalamus, hypothalamus, and basal ganglia. Dissemination of tumor cells in the leptomeninges and the gliotic area and hydrocephalus were also noted.

Expression of Proliferating Cell Nuclear Antigen (PCNA) of Major Intrahepatic Bile Duct Epithelium in Resected Liver Tissue with Hepatolithiasis and Hepatolithiasis Associated with Cholangiocarcinoma.: Shi Nae Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2002;36(4):232-237.

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Abstract PDF: BACKGROUND
Histologic progressive changes of bile duct epithelium with hyperplasia, dysplasia and cholangiocarcinoma could be caused by hepatolithiasis. To be clarified as a neoplastic process, this histologic process should be evaluated with various aspects of cell biology.
METHODS
Immunohistochemical study of proliferating cell nuclear antigen (PCNA) was performed on 45 cases (10; normal, 15; hyperplasia, 14; low-grade dysplasia:LGD, 6; high-grade dysplasia: HGD) of hepatolithiasis and 10 cases (all HGD) of hepatolithiasis with cholangiocarcinoma.
RESULTS
In the hepatolithiasis, mean PCNA labelling indices (LI) of normal, hyperplasia, LGD and HGD of major intrahepatic bile duct epithelium were 24.5+/-4.3, 51.5+/-0.1, 62.0+/-.4 and 84.7+/-.3, respectively and gradually increased. Mean LI of PCNA in HGD of major intrahepatic bile duct epithelium of hepatolithiasis with cholangiocarcinoma was 68.7+/-.7, which was similar to that of LGD in hepatolithiasis without cholangiocarcinoma.
CONCLUSIONS
Histologic transformation through hyperplasia, dysplasia and carcinoma in major intrahepatic bile duct epithelium of hepatolithiasis may be a neoplastic process if these histologic changes are evaluated in the cellular proliferation aspect.

The Observation of Histologic Changes of Major Intrahepatic Bile Duct Epithelium in the Resected Liver Tissue with Hepatolithiasis.: Woon Sup Han, Sae Kyung Choi, Sun Hee Sung; Korean J Pathol. 2001;35(1):20-25.

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Abstract PDF: BACKGROUND
The relationship between hepatoliths and cholangiocarcinoma is etiologically unclear. However, histogenetic sequencing with hyperplasia, dysplasia and carcinoma can occur in the bile ducts of hepatolithiasis.
METHODS
We studied 55 cases of hepatolithiasis and examined the specimens of resected liver tissue with a microscope. The growth patterns of bile duct epithelium were divided into four types: flat, tufting, micropapillary and papillary. The dysplasia was also divided into low-grade dysplasia (LGD) and high-grade dysplasia (HGD).
RESULTS
Of 55 cases of hepatolithiasis, 30 cases (54.6%) were of the flat pattern, 13 cases (23.6%) the micropapillary pattern, and 11 cases (20%) the tufting pattern. Epithelial hyperplasia was noted in only 36 cases (65.5%) in the large bile ducts, but dysplastic changes were found in 19 cases. Of 19 cases of dysplasia, LGD was present in 14 cases (25.5% of total 55 cases) an HGD in 5 cases (9% of total 55 cases). The epithelial hyperplasia showed histologic growth of the flat pattern in 29 cases out of 36 cases. But LGD (14 cases) had 6 cases of the tufting pattern and 7 cases of the micropapillary pattern. HGD (5 cases) revealed 4 cases of the micropapillary pattern with one case of the tufting pattern.
CONCLUSION
This study suggests that sequences of hyperplasia, low-grade dysplasia and high-grade dysplasia can play a role in the carcinogenesis of bile duct epithelium in hepatolithiasis with the histologic pattern changing from flat to micropapillary growth.

Cyclin D1 Protein Expression is Inversely Correlated with p53 Protein in Primary and Recurrent Transitional Cell Carcinoma of the Urinary Bladder.: Min Jin Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(12):1009-1015.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the urinary tract and is characterized by frequent recurrence. Like the other malignant tumor, the genetic alterations leading to neoplastic transformation of the urothelium are related with the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 is a putative protooncogene as cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumor. In this study we performed immunohistochemical stainings of cyclin D1 and p53 in both primary and recurrent transitional cell carcinomas of urinary bladder from 56 patients including 20 cases of recurrent tumor, and compared their results with histopathologic features. The results were as follows. Cyclin D1 immunoreactivity was found in 10 of 10 cases (100%) of grade 1, 25 of 41 (61%) cases of grade 2, and 11 of 25 (44%) cases of grade 3 transitional cell carcinomas. p53 immunoreactivity was found in 40% of grade 1, 63% of grade 2, and 87% of grade 3 lesions. Cyclin D1 expression was significantly higher in Ta and T1 lesions than T2 to T4 by pathologic tumor stage. Conversely p53 immunoreactivity was increased in proportion to the T classification. Cyclin D1 was de creased in recurrent transitional cell carcinomas, compared with primary transitional cell carcinomas. However, there was no statistical significance. In conclusion, cyclin D1 immunoreactivity is associated with low histologic grade and low tumor stage. And there is inverse relationship between the cyclin D1 and p53 overexpression.

Expression of p53 Protein and Ki-67 in Atypical Ductal Hyperplasia, Ductal Carcinoma in Situ, and Microinvasive Ductal Carcinoma of the Breast.: Yi Kyeong Chun, Hye Sun Kim, Yee Jeong Kim, Sung Ran Hong, Hy Sook Kim, Byung Jun Park, Sung Su Kang, Ji Hyun Lee, Sung Kong Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(9):665-672.

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Abstract PDF: Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH). Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found. There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.

Tumor Angiogenesis and Vascular Endothelial Growth Factor Expression in Cervical Intraepithelial Neoplasia.: Hye Jean Park, Hye Jin Park, Hye Sung Moon, Woon Sup Han, Sun Hee Sung; Korean J Pathol. 2000;34(7):524-530.

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Abstract PDF: Angiogenesis is an essential requirement for development, progression, and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) is one of the important angiogenic factors. Recently the role of angiogenesis has been known in premalignant lesions. This study was performed to determine whether the angiogenesis and VEGF expression were increased in association with histological grade of cervical intraepithelial neoplasia (CIN) and to see the relationship between the angiogenesis and VEGF. Immunostainings for factor VIII and VEGF were performed on 52 cases of cervical neoplasia (12 cases of CIN I, 11 cases of CIN II, 15 cases of CIN III, 7 cases of microinvasive squamous cell carcinoma, and 7 cases of invasive carcinoma) and 5 cases of normal cervix. The results showed a significant increase of microvessel count from normal cervix through CIN grades to invasive squamous cell cacinoma. VEGF expression was increased in proportion to the CIN grades. There was no significant correlation between microvessel count and VEGF expression. In conclusion, the tumor angiogenesis is an early event in tumorigenesis of uterine cervix. In addition, no significant relationship between the microvessel count and VEGF expression in CIN suggests the possibility of other growth factors affecting mainly angiogenesis of premalignant lesion of uterine cervix.

Expression of TGF-beta and PDGF in Monocrotaline-Induced Pulmonary Hypertension in Rats.: Min Sun Cho, Sang Ho Cho, Woo Ick Yang, Woon Sup Han; Korean J Pathol. 1999;33(8):545-554.

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Abstract PDF: Pulmonary vascular hypertension is characterized by migration and proliferation of smooth muscle cells accompanying abnormal synthesis and accumulation of extracellular proteins in vascular wall. The aim of this study is to define the role of endogneous TGF-betas and PDGF in the process of remodeling vessels through determining the temporal and spatial distribution of these growth factors in hypertensive pulmonary vessels in monocrotaline-induced pulmonary hypertension in rat. Sprague-Dawley rats were sacrificed 12 hours, 1, 2, 4, 7, 10, 14, 21, 28, and 56 days after treatment. The morphometric analysis of medial thickening and immunohistochemical study using antibodies to TGF-beta1, TGF-beta2, TGF-beta3, and PDGF were performed. Immunoreactivities for TGF-beta1 and TGF-beta3 were increased from the 14th day in the medial smooth muscle cells and PDGF showed increased expression from the 21st day in the medial smooth muscle cells. No difference in TGF-beta2 immunoreactivity was found between control and experimental groups. The expression of TGF-beta1, TGF-beta3 and PDGF increased in medial layers with the progressive thickening of pulmonary arteries which was considered to have close relation to medial hypertrophy of pulmonary arterioles. In the case of PDGF, however, the morphologic change occurred before increase in immunoreactivity was observed in the medial layer of pulmonary arterioles. Moreover, the function of isoforms of TGF-beta has yet to be completely elucidated; the different affinity to receptors and the degree of expression of these receptors that are supposed to affect the function of growth factors. Thus, further studies are needed.

nm23 Protein Immunohistochemical Expression in Colorectal Carcinoma and its Relationship with Other Prognostic Factors.: Shi Nae Lee, Heasoo Koo, Woon Sup Han; Korean J Pathol. 1998;32(6):413-419.

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Abstract: The purpose of this study was to determine the immunohistochemical expression of nm23-H1, a putative metastatic suppressor gene, and to correlate its expression with clinicopathologic variables in 75 cases of surgically resected colorectal carcinomas. There appeared to be a trend between increasing relative nm23 protein expression and Dukes' stage, vessel invasion, and metastasis of lymph nodes. nm23 was expressed in 67 cases (89.3%) and increased in cases with lower Dukes' stage (P<0.05) and in cases without vessel invasion (P<0.01) or lymph node metastasis (P<0.01). No significant relationship was observed between the nm23 protein expression and other parameters, such as tumor size, location and differentiation of the tumor. The results suggest that the nm23 protein expression plays a role in the suppression of nodal metastasis and vessel invasion in colorectal carcinomas.

A Study for IL-6, IL-13 and TIMP-3 Expressions of Placenta, Fetus and Endometrium in Pregnant Mice after Treatment with Lipopolysaccharide.: Sung Ran Hong, In Gul Moon, Ju Young Seoh, Yee Jeong Kim, Sung Sook Kim, Woon Sup Han; Korean J Pathol. 1998;32(5):352-361.

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Abstract: We examined C3H pregnant mice at 15 days (70% gestation) after treatment of lipopolysaccaride (LPS) to observe the changes of IL-6 concentration in maternal serum and amniotic fluid and expression of IL-6, IL-13 & TIMP-3 in placenta, fetus and endometrium, and to investigate the correlation among IL-6, IL-13 and TIMP-3. The results were as follows: 1) IL-6 in serum and amniotic fluid after treatment of LPS was significantly elevated; peaked at 1, 2, 4, 5 hours and decreased to control level at 8 hours (P<0.05). IL-6 in placental disc, chorioamnionic membrane, fetus, decidua and endometrial epithelium was overexpressed significantly at 1, 2, 4 hours after treatment of LPS (P<0.05). IL-6 overexpression was more significantly increased in maternal tissue than fetal tissue (P<0.05). 2) Increased concentration of amniotic fluid IL-6 was equally originated from transplacental crossage of maternal serum IL-6, and direct local production of IL-6 from placenta, fetus and endometrium (P<0.05). 3) IL-13 in placental disc, chorioamnionic membrane, fetus, decidua and endometrial epithelium was overexpressed after treatment of LPS, but not significant statistically. 4) TIMP-3 was overexpressed in placental disc, chorioamnionic membrane, fetus and decidua. TIMP-3 overexpression was more significant in placental disc than other tissues (P<0.05). 5) Overexpressions in IL-13 and IL-6 revealed direct proportional correlation coefficient (Spearman correlation coefficient, 0.5212 ; P<0.05). IL-6 expression was a head of overexpression of TIMP-3, but not significant. In conclusion, all of IL-6, IL-13 and TIMP-3 relate with inflammatory response, especially IL-6 in maternal serum, amniotic fluid and tissue of placenta, fetus and endometrium was so sensitive that it can be an indicator for antenatal diagnosis of chorioamnonitis, and amniotic fluid IL-6 is equally originated from maternal serum and from tissue of placenta, fetus and endometrium. IL-13 and TIMP-3 may have parallel correlation to the IL-6 in fetal and maternal tissue after treatment of LPS.

Expression of Alpha Smooth Muscle Actin and Lysozyme in Various Glomerular Diseases.: Sun Hee Sung, Woon Sup Han; Korean J Pathol. 1998;32(1):51-57.

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Abstract PDF: The cells of glomerular mesangium is composed mostly of intrinsic contractile mesangial cells and a few macrophages. Injury to the mesangium is central to many glomerular diseases. This study was aimed to evaluate and compare the expressions of alpha-smooth muscle actin (ASMA) and lysozyme in the mesangium of various human glomerular diseases and also of according to the severity of their progressions. We performed immunohistochemical and transmission electromicroscopic examinations in 51 cases of renal biopsy including 5 normal kidneys. The results were as follows; (1) ASMA staining was negligible in normal glomeruli. (2) Increased ASMA staining was observed in the mesangium of glomeruli from all specimens of primary glomerular disease, regardless of their diagnosis. (3) The staining intensity of ASMA in mesangium was mild in minimal change disease and membranous glomerulonephritis, and strong in focal segmental glomerulosclerosis (FSGS), diffuse mesangial hypercellularity, membranoproliferative glomerulonephritis (MPGN), and IgA nephropathy (IgAN). (4) The staining intensity of ASMA have no correlation with mesangial immune deposits. (5) The staining intensity of ASMA in mesangium was inversely correlated with the disease progression in FSGS and IgAN. (6) Glomeruli showing global or segmental sclerosis invariably lacked ASMA. (7) Compared with ASMA, the mesangial cells with lysozyme expression were very rare, even though it was in proportion to ASMA staining. Interstitial ASMA expression was confined to fibrotic area in various glomerular diseases. In conclusion, the expression of ASMA and lysozyme in mesangium are increased in a variety of glomerular diseases, regardless of disease entity. Their intensity was in proportion to the mesangial cell proliferation. In progressive glomerulonephritis, such as IgAN and FSGS, the increased expression of ASMA was prominent in the early lesion, and decreased with the progression of the glomerular sclerosis.

p53 Immunoreactivity in the Cytology of Body Cavity Fluid.: Sun Hee Sung, Woon Sup Han; Korean J Cytopathol. 1998;9(1):15-20.

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Abstract PDF: Mutant form of the p53 gene product is abnormally accumulated in the nuclei of the tumor cells due to prolonged half life, and readily detected by immunohisto- chemical methods. To determine the positivity rate of p53 in body cavity fluid according the primary site and histological types of tumors and the utility of p53 immunostaining as an adjunct in the diagnosis of malignancy, we reviewed 69 effusions, including pleural effusion, ascitic fluid, and pericardial fluid, that were diagnosed as overt malignancy and 21 effusions of suspicious malignancy. Immuno- histochemistry was performed on paraffin-embedded cell blocks using a monoclonal antibody to p53 supressor gene product(Clone DO7) and a standard avidin-biotin complex technique with a citrate buffer antigen retrieval solution. The results were as follows; of the 46 pleural effusions with overt malignancy, 22 were immunopositive for p53 protein; of the 21 ascitic fluids with overt malignancy, 5 were positive for p53. Positivity rates according to the primary sites of tumors were 18 of 34(52.9%), 8 of 21(38.1%), 1 of 9(11.1%) cases of the tumors of the lung, GI tract, and ovary, respectively. According to the histologic types of lung cancer, 11 cases(61.6%) were positive out of 18 adenocarcinomas, 2 of 5 large cell undifferentiated carcinomas, and 1 of 2 small cell undifferentiated carcinomas. Of 21 cases of suspicious malignancy, 6 were positive for p53 and all of them(6/6) were confirmed as adeno- carcinoma of the lung or GI tract. These findings indicate that p53 immunostaining using paraffin embedded cell block is useful diagnostic and prognostic marker in body fluid cytology although negative immunostaining does not exclude malignancy.

Fine Needle Aspiration Cytology of Osteoclastic Giant Cell Tumor of the Pancreas.: Sun Hee Sung, Woon Sup Han; Korean J Cytopathol. 1998;9(1):89-94.

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Abstract PDF: A case of fine needle aspiration cytology of an osteoclastic giant cell tumor of pancreas, which is an uncommon variant of ductal adenocarcinoma, is described. Aspirated tumor cells were characterized by three populations: (1) bland osteoclast like giant cells with multiple small, round nuclei with distinct nucleoli, and abundant cytoplasm, (2) individually scattered or loosely clustered medium sized mononuclear tumor cells, having fine chromatin, smooth nuclear membrane, often prominent nucleoli, and high N/C ratio, (3) bland or atypical spindle shaped cells. Osteoid like lacy material was also seen on cell block section. The immunohistochemical studies using paraffin embedded cell block section showed positivities for vimentin and lysozyme in both giant and mononuclear tumor cells. However, they were negative for cytokeratin, epithelial membrane antigen, S-100 protein, carcinoembryonic antigen, and p53.

Taxol-induced Pathological Findings in Rat Small Intestine.: Sun Hee Chang, Shi Nae Lee, Hee Soo Yoon, Min Sun Cho, Hea Soo Koo, Woon Sup Han; Korean J Pathol. 1997;31(12):1291-1296.

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Abstract PDF: Taxol is an active chemotherapeutic agent against a variety of solid tumors and a potentially useful drug for augmenting the cytotoxic action of radiotherapy against certain cancers. Taxol blocks cells in the mitotic phase of cell cycle. The aim of this study was to define the in vivo response of rapidly dividing cells of the small intestinal mucosa to taxol. We studied the numbers of apoptotic and mitotic cells and the expression of bcl-2 and p53 in rat jejunal crypt cells at 1, 2, 4, 8, 12, 16, and 24 hours and 3 and 5 days after intraperitoneal injection of taxol. Mitosis peaked at 2 and 4 hours and 12 and 16 hours. Apoptosis peaked at 16 hours and returned to normal after five days. The glands in crypts showed marked distortion with atypical lining cells after three days, which returned to normal at 5 days. bcl-2 expression was markedly decreased at 8 to 24 hours and subnormally recovered after three to five days. p53 showed no significant changes throughout. The histopathological changes in small intestine due to taxol were transient with complete recovery. bcl-2 expression was inversely corresponded to numbers of apoptosis. The changes were p53 independent. Further studies to understand the conditions that maximize the cell-cycle modulating effects of taxol cl-may greatly enhance its anti-tumor effectiveness.

CD34 Antigen Expression in Gastrointestinal Stromal Tumors.: Sun Hee Sung, Min Sun Cho, Woon Sup Han; Korean J Pathol. 1997;31(11):1166-1171.

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Abstract: Gastrointestinal stromal tumor (GIST) is known as considerable controversal tumor about it's histogenesis, differentiation and biologic behavior. It is traditionally regarded as smooth muscle tumor. To evaluate and clarify the origin of tumor, we performed immunohistochemical study of 23 cases of GIST on CD34 antigen, alpha-smooth muscle actin, S-100 protein, and compared the result with 4 cases of typical leiomyoma of GI tract. The results were as follows. CD34 antigen expression was noted in 21 cases (91.3%) of GIST, while typical leiomyoma was all negative. There were no difference of CD34 expression according to the biologic behavior. However, it's staining pattern was significantly different (p<0.05). Focal or multifocal expression was dominant in benign GIST (58.3%), while diffuse expression was dominant in malignant GIST (80%). Actin was expressed in 5 cases of benign GIST (38.5%) and 1 of malignant GIST (16.7%) focally. All typical leiomyoma showed diffuse strong positivity on alpha-smooth muscle actin. S-100 protein was expressed in 2 cases of benign GIST (16.7%) only. The pattern of CD34 expression was focal in the actin or S-100 protein positive cases. In conclusion CD34 antigen is useful marker in the separation of GIST, from typical smooth muscle tumor. Also it suggest that most GISTs are histogenetically primitive mesenchymal cell origin. However, CD34 expression was unrelated with biologic behavior of GIST.

Melanosis Coli: Relation to Apoptosis in Pathogenesis.: Sun Hee Sung, Hea Soo Koo, Woon Sup Han; Korean J Pathol. 1996;30(7):570-575.

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Abstract PDF: Melanosis coli is characterized by a dark brownish discoloration of the colonic mucosa. Its pathogenesis is still unknown. Recently it was proposed that the apoptosis of mucosal epithelium due to habitual use of laxatives play an important role for induction of melanosis coli. We studied clinicopathologic aspects of 12 cases of melanosis coli and analysed the histochemical and immunohistochemical characteristics of them. Results are as follows. : Mean patient's age was 53.5, and the male:female ratio was 4:8. Nine patients had a history of constipation, and all of these had administrated various kinds of laxatives. The severity of discoloration was correlated with the duration of constipation and age. There was no difference of anatomical distribution in colon. Other remarkable mucosal lesions were not accompanied. On pathologic examination, all cases showed frequent yellow-brown pigment laden cells in lamina propria. These pigments were positive for periodic acid Schiff stains, Fontana Masson stains, and Victoria blue stains, however they were negative for prussian blue stain. On immunohistochemical stainings pigmented cells were positive for CD68, and negative for S-100 protein and neuron specific enolase. These results indicate that they are macrophages. On ultrastructural examination pigmented cytoplasms were filled with variable sized electron dense granules including irregulary round deformed membranous structures, lipid vacuoles. Apoptosis of mucosal epithelium was noted in 5 cases. These findings suggest that apoptosis is the significant pathologic process in the progression of some cases of melanosis coli.

Significance of Ultrastructural Electron Dense Deposits on Glomerular Capillary Loops in IgA Nephropathy.: Sun Hee Sung, Ok Kyung Kim, Woon Sup Han; Korean J Pathol. 1996;30(1):32-39.

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Abstract PDF: To evaluate the clinical and histopathological significance of electron dense deposits on capillary in IgA nephropathy, we reviewed and compared the clinical, laboratory, and pathological features of the patients with IgA nephropathy without loop extension of electron dense deposits(Group I, 91 cases) and IgA nephropathy with loop extension(Group II, 17cases) by ultrastructural examination using transmission electron microscope. IgA nephropathy associated with liver disease, Henoch-Schonlein purpura, systemic lupus erythematosus and the other IgA nephropathies associated with systemic diseases were excluded. The results were as follows; 1) There was no significant difference in age distribution. 2) Generalized edema was more common in group II. 3) Nephrotic ranged proteinuria(>3 g/24hr urine) was more prominent in Group II(52.9%) than Group I(8.8%). 4) Among the groups, segmental or mild deposits on the loops were noted in 13 cases, and severe and generalized deposits in 4 cases. Subendothelial deposits were noted in 6 cases, subepithelial deposits in 3 cases, subendothelial with intramembranous deposits in 1 case, subendothelial with subepithelial deposits in 1 case, intramembranous with subepithelial deposits in 2 cases, and subendothelial, subepithelial and intramembranous deposits in 4 cases. 5) The other associated ultrastructural changes of group II were diffuse effacement of foot processes with microvillous transformation, swelling or vacuolar degeneration of podocytes and glomerular endothelium. 6) According to the WHO morphologic criteria, the grade of Group II was significantly higher than Group I. From the above results, it can be concluded that the extension of electron dense deposits along the capillary loops in the cases of IgA nephropathy is highly correlated with proteinuria in the nephrotic ranged. It seems to be a poor prognostic indicator in view of the facts that it correlats with high histopathologic grading.

Application of Epstein-Barr Virus Cell Lines (CCL85 EB-3) in Performing the EBER mRNA In Situ Hybridization as a Positive Control.: Sung Sook Kim, Woon Sup Han, Joo Young Suh, Joo Ryung Huh; Korean J Cytopathol. 1996;7(1):38-43.

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Abstract PDF: Epstein-Barr virus(EBV) is associated with a wide spectrum of benign and malignant disorders including leukoplakia, Hodgkin's lymphoma, central nervous system lymphoma, peripheral T cell lymphoma and nasopharyngeal undifferentiated carcinoma. There are several distinctive aspects of biology of the virus that are important in investigation of virus in clinical specimens. The abundant expression of the EBER mRNA transcripts makes possible the sensitive detection of latent expression in EBV-associated tumors. Although there has been a dramatic increased interest in the direct characterization of EBV in clinical specimens, there have been few studies about the effective and reliable positive controls in performing in situ hybridization technique for EBV, especially on paraffin-embedded tissue. We applied Burkitts lymphoma cell line as positive control in EBV in hydridization using Oncor Kit. The cell block of Burkitt lymphoma cell line(CCL85 EB-3) showed strong and specific positivity for EBER in situ in nuclei of EBV infected cells.

Immunohistochemical Study of IL-4, IL-6, and TNF Expression in Cardiac Myxoma: Emphasis on Constitutional Symptoms of the Myxoma Patients.: Min Sun Cho, Soo Yeon Cho, Mi Jung Kim, Sung Sook Kim, Jeong Wook Seo, Woon Sup Han; Korean J Pathol. 1995;29(5):563-571.

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Abstract: It is well documented that cardiac myxomas are associated with immunologic features that can simulate systemic autoimmune diseases. Recently, it was reported that cardiac myxomas produce IL-6 constitutively, which could partly explain the immunologic features observed in these patients. However, only a few investigators have studied cytokines in regards to symptoms they may cause in patients with cardiac myxoma. Also there is very little information in the literature on the immunohistochmical localization of IL-6. We performed immunobistochemical stains for IL-4, TNF, and IL-6 on paraffm embbeded tissue of cardiac myxoma tissue. A bioassay of IL-6 activity in patient's serum and in cultured cells from fresh myxoma tissue was performed to ascertain the role of these cytokines in myxomas. In this study, we demonstrated inununohistochemically that there was a local overproduction of IL-4, TNF, and IL-6 in cytoplasm of the tumor cells in about half cases. Bioassays of the serum and cultured tumor cells revealed elevated IL-6 activities. Also these findings correlate to production of patient's constitutional symptoms with statistical significance (P<0.05). In conclusion, these results are of considerable importance in understanding the role of IL-4, TNF, and IL-6 in cardiac myxoma patient with constitutional symptoms, and have an impact on strategies for diagnosis and therapy of cardiac myxoma.

Expression of Interleukin-6 in Induced Viral Myocarditis in Mice.: Soo Yeon Cho, Hye Kyung Jin, Min Sun Cho, Sung Sook Kim, Woon Sup Han, Dong Sun Han, Hak Chung Lee; Korean J Pathol. 1995;29(2):212-220.

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Abstract PDF: Viral myocarditis is considered an important cause of dilated cardiomyopathy. At preseent, two mechanisms are known to be involved in the pathogenesis of viral myocarditis and subse-quent cardiomyopathy: viral direct toxicity and immune mediated toxicity. Some authors have reported that IL-6 influences the immunologic mechanism and the virus-induced tissue damage in myocarditis. We injected encephalomyocarditis(EMC) virus to induce viral myocarditis in ICR mice. In order to study the lymphocyte subset and IL-6 expression to clarify the immune mechanism and to demonstrate the role of IL-6 in viral induced myocardial damage. The following results were obtained: 1) In virus inoculated mice, inflammation was severest at 10 days, and some serious complications developed, indicating a possible transition to dilated cardiomyopathy. 2) On analysis of the lymphocyte subset, CD4 cells were most prevalent at 5 days and CD8 cells were most prevalent at 10 and 20 days. 3) IL-6 was significantly increased and expression of IL-6 was constant, but its intensity was strongest at 5 days. In conclusion, IL-6, produced by inflammatory cells, fibroblasts, and endothelial cells, might play an important role in myocardial damage in experimentally induced EMC viral myocarditis by its direct cytotoxicity or cytokine mediated activation of cytotoxic cells.

Inflammatory Pseudotumor of the Lymph Node: A case report.: Yee Jeong Kim, Kun Chang Song, Woo Hee Jung, Woon Sup Han; Korean J Pathol. 1993;27(2):164-168.

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Abstract PDF: A 21-year-old man presented with a 7 days history of fever. Careful clinical examination led to the discovery of left supraclavicular lymphadenopathy without hepatosplenomegaly. Serologic tests for Ebstein-Barr virus, HIV, hepatitis type B & C, syphilis and typhoid fever were negative. Blood, urine, and stool cultures yielded no growth. Histologically, the process mainly involved the connective tissue framework of the lymph node, sharing the features of inflammatory pseudotmor(IPT) of other organs: a storiform growth pattern, increased vascularity with associated vascular lesions, and a polymorphous inflammatory infiltrate in a collagen-rich stroma. Immunohistochemical study for spindle cells showed positive reaction for actin and vimentin but not for desmin, and lymphoid cells revealed polyclonality. Characteristics of mass formation, and the inflammatory nautre of the process enabled us adopt the term IPT which should be differentiated from hematolymphoid proliferative disorder or mesenchymal neoplasia.

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