Journal of Pathology and Translational Medicine

Han Ik Bae

14 Articles

Detection of JC Virus T-Ag in Early Gastric Cancer.: Eun Jeong Jang, Jung Sik Jang, Jae Hoon Kim, Han Ik Bae, In Soo Suh; Korean J Pathol. 2010;44(5):456-461.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.456

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BACKGROUND
JC virus (JCV) is a polyomavirus that commonly infects humans and can cause progressive multifocal leukoencephalopathy in immunocompromised patients. Recently, many reports have documented detection of JCV in gastrointestinal tract cancers. We investigated the presence of JCV in gastric adenocarcinoma, adenoma, and non-neoplastic gastric mucosa.
METHODS
We selected paraffin-embedded tissue from endoscopic mucosal resections performed from January 2007 to September 2008. DNA was extracted from the paraffin-embedded specimens of 30 adenocarcinomas, 20 adenomas of the stomach, and 20 non-neoplastic gastric mucosa. Polymerase chain reaction amplifications were performed using gene-specific primers to detect the JCV gene sequences, and immunohistochemical staining was performed to detect the T-antigen (T-Ag) protein.
RESULTS
The T-Ag sequence was detected in nine of 30 gastric cancers (30%), two of 20 adenomas (10%), and eight of 20 non-neoplastic gastric mucosa specimens (40%). T-Ag protein expression was found in five of 30 gastric cancers (16.7%) and one of 20 non-neoplastic gastric mucosa specimens (5%), whereas no expression was observed in any of the adenomas.
CONCLUSIONS
Although we could not detect a correlation between JCV and gastric cancer, we demonstrated the presence of JCV T-Ag expression in human gastric cancers. These findings suggest a possible role for JCV in gastric carcinogenesis.

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Associations Between Gastric Cancer Risk and Virus Infection Other Than Epstein-Barr Virus: A Systematic Review and Meta-analysis Based on Epidemiological Studies
Hui Wang, Xiao-Long Chen, Kai Liu, Dan Bai, Wei-Han Zhang, Xin-Zu Chen, Jian-Kun Hu
Clinical and Translational Gastroenterology.2020; 11(7): e00201. CrossRef

An Approach to Diagnosing Gastrointestinal Stromal Tumors Using Immunohistochemistry of c-kit and PDGFRA with Molecular Analysis.: Jeong Shik Kim, Jae Hoon Kim, Hyun Jin Oh, In Soo Suh, Jong Gwang Kim, Byung Wook Kang, Wan Sik Yu, Ho Young Chung, Han Ik Bae; Korean J Pathol. 2010;44(2):173-178.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.173

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Abstract PDF: BACKGROUND
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis.
METHODS
We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues.
RESULTS
Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11.
CONCLUSIONS
Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.

Predictive Factors of Epstein-Barr Virus Association in Gastric Adenocarcinoma.: Young Su Kim, Sang Chul Nam, Man Hoon Han, Ji Yun Jeong, Sun Kyun Park, In Soo Suh, Han Ik Bae; Korean J Pathol. 2008;42(4):193-197.

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Abstract PDF: BACKGROUND
It is important to detect Epstein-Barr virus (EBV) in the setting of gastric cancer so that early viral targeted therapy and prevention can be undertaken. The aim of this study was to investigate the predictive clinicopathologic factors for EBV-related gastric cancer.
METHODS
The archival tumor tissues from 335 patients with gastric cancer were examined using tissue microarray. The detection of EBV was performed using EBV mRNA in situ hybridization (EBV-ISH), and the results were compared against clinicopathologic factors.
RESULTS
EBV-related gastric cancers were identified in 21 of 335 investigated cases (6.27%). The anatomical predisposition of EBV-related cancers to manifest in the upper stomach was statistically significant (p<0.001). EBV-related cancers were almost always (20/21) accompanied by lymphoid stroma. No differences in age, sex, histologic differentiation, or T or N stage were noted between EBV-positive and EBV-negative gastric carcinomas.
CONCLUSIONS
The association of EBV with gastric adenocarcinomas could be predicted when tumors with lymphoid stroma occurred in the upper stomach.

Genetic Expression Pattern of Gastric Carcinomas According to Cellular Mucin Phenotypes.: Won Ae Lee, In Soo Suh, Ying Hua Li, Ji Hyun Eum, Wan Sik Yu, Han Ik Bae; Korean J Pathol. 2007;41(5):307-315.

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Abstract PDF: BACKGROUND
Gastric carcinomas (GCs) have recently been reclassified according to the mucin phenotypes. We aimed to characterize the relationship between the mucin phenotypes and the genetic alterations or the clinicopathologic parameters of GCs.
METHODS
Immunohistochemistry was performed for MUC1, MUC5AC, MUC6, MUC2, CD10, p53, hMLH1, CerbB2 and E-cadherin in 150 GCs. The mucin phenotypes of the GCs were classified as 4 phenotypes: gastric, intestinal, mixed and unclassified.
RESULTS
MUC1, MUC5AC, MUC6, MUC2 and CD10 were expressed in 63.3%, 42.7%, 14.0%, 24.7% and 14.0% of the GCs, respectively. The mucin phenotypes of the GCs corresponded to the gastric type in 31.3%, the intestinal type in 20.0%, the mixed type in 15.3% and the unclassified type in 33.3%. The incidence of a p53 overexpression was higher in the gastric or mixed phenotype than in the intestinal or unclassified phenotype. MUC5AC expression, p53 overexpression and the gastric or mixed phenotype were associated with poor patient survival by multivariate analysis.
CONCLUSION
This study suggests the gastric or mixed mucin phenotype may more likely go through the p53 pathway in carcinogenesis and the mucin phenotype may be considered as a prognostic indicator.

Diffuse Ganglioneuromatosis of Appendix associated with Von Recklinghausen;s Disease.: Young Su Kim, Sang Chul Nam, Man Hoon Han, Jeong Shik Kim, Ji Yun Jeong, Han Ik Bae; Korean J Pathol. 2007;41(5):334-336.

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Abstract PDF: Gastrointestinal ganglioneuromatosis is a rare neoplastic condition that can occur in association with von Recklinghausen's disease with multiple endocrine neoplasia type II B. The main locations are the ileum, colon, and appendix. We report a case of diffuse ganglioneuromatosis of the appendix associated with a mesenteric and ileocecal plexiform neurofibroma in von Recklinghausen's disease.

Two Cases of Strongyloidiasis Diagnosed by Colonoscopic Biopsy.: Sang Chul Nam, Man Hoon Han, Young Su Kim, Yoon Seup Kum, In Soo Suh, Han Ik Bae; Korean J Pathol. 2007;41(5):343-346.

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Abstract PDF: Strongyloides stercoralis is an intestinal nematode that is able to infect the host tissue and persist for many years through autoinfection, and it causes life-threatening hyperinfection in immunocompromised hosts. We report here on two cases of strongyloidiasis that were diagnosed by colonoscopic biopsy. One case was a 73-year-old woman who was hospitalized with complaints of melena. She was being treated with corticosteroid due to her asthma and rheumatoid arthritis. The other case was a 63-year-old man who suffered with abdominal discomfort and severe loss of body weight (18 kg) for 2 months. In both cases, colonoscopic examination revealed polyps and petechiae at the entire colon. Microscopically, a small illdefined granuloma with a longitudinally sectioned parasite was seen on the colonoscopic biopsy. Endoscopic examination was done after suspecting parasitic infestation. The gastric and duodenal mucosa showed numerous cross sections of adult worms, eggs and larvae that were developing in crypts. Even if such a patient is in an asymptomatic state, this illness must be treated due to the potential for fatal autoinfection.

A Standardized Pathology Report for Colorectal Cancer.: Hee Jin Chang, Cheol Keun Park, Woo Ho Kim, Young Bae Kim, Youn Wha Kim, Ho Guen Kim, Han Ik Bae, Kyu Sang Song, Mee Soo Chang, Hee Kyung Chang, Yang Seok Chae; Korean J Pathol. 2006;40(3):193-203.

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Abstract PDF: BACKGROUND
AND METHODS: For standardizing the pathology report and diagnosis of colorectal cancers, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has developed a pathology reporting format for colorectal cancer in collaboration with the Korean Society of Coloproctology.
RESULTS
The diagnostic parameters are divided into two parts: the standard part and the optional part. The standard part contains most of the items listed in the Japanese classification, the TNM classification by AJCC, and the WHO classification. We included detailed descriptions on each item.
CONCLUSIONS
The standardized pathology report for colorectal cancers is adequate for its application to routine surgical pathology reports, and it is also helpful to decrease the discrepancies that occur during the pathologic diagnosis of colorectal cancer. Furthermore, this reporting format could encourage nationwide multi-center collaborative studies.

The Status of Pathology Specimen Bank in Other Countries.: Han Ik Bae, Ghil Suk Yoon; Korean J Pathol. 2005;39(6):379-383.

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Abstract PDF: Pathology specimen has been collected for purposes of education and research, particularly with respect to basic, developmental and translational studies in many areas of cancer research including molecular biology, immunology, and genetics. Even though no policy or ethical guideline drafted to regulate research tissue bank in Korea, advanced countries has been concerned ethical issues in the collections, storages, specimen transports and informatics for pathology specimen bank. Informed consent and confidentiality for protection of personal data records, which can be directly or indirectly associated with linked data from the donors' point of view, are the key to banking all over the world. The institutional review board (IRB) is important to ensure the scientific and ethical quality of pathologic specimen research. Increasing molecular genetic testing is also resulting in an increased demand of quality control for high quality nucleic acids. Most recently, the use of stored human tissue for education and research has become an object of increased ethical concern in Korea. Korean Association of Pathologists (KAP) has in urgent need of the policies and a standardized operating procedure, regulating a good collection practice of pathology specimen bank.

Expression Patterns of Tumor Related Proteins for Differential Diagnoses of Intrahepatic Adenocarcinomas.: Ghil Suk Yoon, Mi Sung Kim, Young Hwa Li, Ji Hyun Uhm, Sun Ju Kim, Tae Sook Kim, In Su Suh, Han Ik Bae; Korean J Pathol. 2005;39(4):229-235.

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Abstract PDF: Background
: Differential diagnoses of intrahepatic adenocarcinomas (IHAC) play an important role in the detecting primary sites and the determining type of treatment and overall prognosis of the patient. However, histopathologic findings alone have limitations of differential diagnoses of IHAC. Methods : To clarify which tumor related proteins (TRP) are useful for differential diagnoses of IHAC, TRP expression were investigated immunohistochemically, using MUC5AC, MUC2, mAb 91.9H, MUC1, and pS2, and by high iron diamine (HID) staining in 61 clinically confirmed IHACs. Results : MUC5AC (9/18, p<0.05) and MUC1 (17/18, p>0.05) displayed the most frequent expression in cholangiocarcinomas, and MUC2 (11/18, p<0.05), mAb 91.9H (16/18, p<0.05), and HID (16/18, p<0.05) in colorectal adenocarcinomas. pS2 (3/11, p>0.05) was expressed more often in pancreatic adenocarcinomas than other IHAC, while MUC2 and 91.9H were not expressed at all in pancreatic adenocarcinomas. The positivity of several TRP did not correlate with tumor differentiation. Conclusions : MUC5AC, MUC2, mAb 91.9H, and HID may be useful in differentiating cholangiocarcinomas from colorectal adenocarcinomas.

A Standardized Pathology Report for Gastric Cancer.: Woo Ho Kim, Cheol Keun Park, Young Bae Kim, Youn Wha Kim, Ho Guen Kim, Han Ik Bae, Kyu Sang Song, Hee Kyung Chang, Hee Jin Chang, Yang Seok Chae; Korean J Pathol. 2005;39(2):106-113.

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Abstract PDF: BACKGROUND
AND METHODS: The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists developed a standardized pathology reporting format for gastric cancer in collaboration with the Korean Gastric Cancer Association. RESULTS: The diagnostic parameters are divided into two part: the standard part and the optional part. The standard part contains most of the items listed in the Japanese classification, the TNM classification by UICC, the WHO classification, and the Korean Gastric Cancer Association classification. Therefore, the standard part is adequate for routine surgical pathology service. We included detailed descriptions on each item.
CONCLUSIONS
The authors anticipate that this standardization can improve the diagnostic accuracy and decrease the discrepancies that occur in the pathologic diagnosis of gastric cancer. Furthermore, the standard format can encourage large scale multi-institutional collaborative studies.

The Effect of Ischemic Preconditioning in Rat Liver: The Expression of Interleukin-1 and Nuclear Factor-B.: Kum Yoon Seup, Soo Kyoung Lee, Sun zoo Kim, Eun Kyoung Kwak, Ji Young Park, Tae In Park, Han Ik Bae, Yoon Kyung Sohn, In Soo Suh; Korean J Pathol. 2002;36(4):238-242.

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Abstract PDF: BACKGROUND
A short period of ischemia and reperfusion, called ischemic preconditioning, protects various tissues against subsequent sustained ischemic insult. Apoptosis of hepatocytes and sinusoidal endothelial cells are a critical mechanisms of injury in the ischemic liver. Because nuclear factor-B (NF-B) has a significant role in the cell survival, we hypothesized that ischemic preconditioning protects by inhibition of apoptosis through the expression of NF-B, induced by interleukin-1 (IL-1), which is known for enhancement of its transcription and activation.
METHODS
We induced ischemia and reperfusion on rat liver, and performed in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labelling assay and polymerase chain reaction for IL-1 mRNA and NF-B mRNA.
RESULTS
Apoptosis of hepatocytes and sinusoidal endothelial cells, assessed by in situ TUNEL assay, was significantly reduced with preconditioning. The expression of IL-1 mRNA and NF-B mRNA are seen on discrete monoclonal bands around 344 and 356 base pairs, in comparison with normal rat liver, but, there was no significant difference between the ischemia-reperfusion group and the preconditioning group.
CONCLUSIONS
We suggest that ischemic preconditioning confers dramatic protection against prolonged ischemia via inhibition of apotosis through the expression of IL-1 inducing NF-B and its activation. However, we need further study in the activity of NF-B, such as nucleotide shift assay, because the activity of NF-B is regulated by binding of the inhibitory protein, IB.

Molecular Diagnosis of Cutaneous T Cell Lymphoproliferative Diseases.: Ji Young Park, Myung Hoon Lee, Eun Kyung Kwak, Dong Ja Kim, Tae In Park, Han Ik Bae; Korean J Pathol. 2000;34(11):941-949.

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Abstract PDF: It is often problematic to diagnose T-cell lymphoproliferative disorders of the skin because of the difficulty in establishing clonality in paraffin-embedded tissue. We used polymerase chain reaction single strand conformational polymorphism (PCR-SSCP) and heteroduplex analysis in paraffin embedded tissue to detect clonal rearrangement of T-cell receptor gamma (TCRgamma) gene in 17 T-cell lymphoproliferative disorders and 6 atypical lymphoproliferative diseases. We used polymerase chain reaction to detect TCR beta gene rearrangement in 8 of 17 cases which did not show TCRgamma gene rearrangement. Jurkat cell lines were used as monoclonal controls. DNA was extracted from 5 biopsies of T-cell lymphomas, 10 biopsies of mycosis fungoides, 2 biopsies of lymphomatoid papulosis, and 6 biopsies of atypical lymphoproliferative lesions. We detected monoclonality in 5 of 5 T-cell lymphoma cases, 2 of 2 lymphomatoid papulosis cases, 6 of 10 mycosis fungoides cases, and 2 of 6 atypical lymphoproliferative disease cases. We conclude that nonradioactive PCR-SSCP for TCR gene rearrangement analysis is a useful adjunct to routine histological and immunophenotypic methods in the diagnosis of cutaneous T cell lymphoproliferative disorders in paraffin embedded tissue.

Expression of H-ras, erb B2, and p53 Proteins in Gastric Intestinal Metaplasia Associated with Cellular Atypism.: Han Ik Bae, Dong Hoon Kim, Jung Ran Kim; Korean J Pathol. 1997;31(9):862-872.

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Abstract PDF: Intestinal metaplasia (IM) have long been thought to play a role in the pathogenesis of gastric intestinal adenocarcinoma, but not in that of diffuse cancer. We studied 20 normal gastric mucosa, 90 IM, 39 atypia (dysplasia or adenoma), and 51 adenocarcinoma to evaluate the expression of p53, erb B2, and H-ras p21 proteins and to assess the correlation with IM (esp. type III IM, revealing positive HID-AB/PAS for sulfomucin). Positive rate of HID-AB staining revealed an increased trend in comparison between IM, atypia and adenocarcinoma. It was the highest in mucinous carcinoma, but it was not correlated with positive oncoprotein expressions. Positive rates of oncoproteins revealed increased trends in comparison between IM, dysplasia or adenoma and adenocarcinoma in c-erb B2 and p53 (P<0.01). The positive rates were highest in intestinal adenocarcinoma (50.0% and 54.2%, respectively). Rates were lowest in biopsy tissue of IM (4.4% and 8.7%, respectively). The expression of H-ras p21 was not significant in gastric carcinogenesis. There was no significant correlation between oncoproteins and other clinical parameters, such as depth of invasion, differentiation, size and nodal metastasis of the tumors. Therefore, we suggest that p53 and erb B2 may play a role in the carcinogenesis of gastric intestinal adenocarcinoma.

Microvessel Quantification, Expression of p53 Protein and MIB-1 in Colorectal Adenoma and Carcinoma.: Tae Jung Jang, Jung Ran Kim, Han Ik Bae; Korean J Pathol. 1997;31(1):40-50.

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Abstract PDF: Angiogenesis is a crucial step in tumor growth and progression. Scarce data is available on angiogensis in gastrointestinal tumors. We studied 16 normal colon, 44 adenomas and 29 carcinomas to evaluate angiogenesis in colorectal tumors and to assess the correlation among p53 protein, proliferative activity and other clinical prognostic parameters. Endothelial cells were immunostained with an anti-Factor VIII mAb; in each case three microscopic fields(x 200) were counted: average number of the three fields was defined as microvessel density (MVD). p53 protein expression was 45.5%(20/44) in adenomas, and 79.3%(23/29) in carcinomas (p<0.01). p53 protein expression of carcinomas was 57.1%(4/7) in diploid tumors, 100%(8/8) in aneuploid tumors (p=0.07), 100%(8/8) in well differentiated tumors, and 50%(2/4) in poorly differentiated tumors (p=0.09). MIB-1 score was 2.3+/-0.7(38) in adenomas, 3.4+/-0.5(29) in carcinomas (p<0.01). There was no significant correlation between p53 protein and MIB-1 score. MVD was 10.4+/-4.1(16) in the normal mucosa, 21.5+/-7.9(39) in the adenomas, 35.3+/-9.7(26) in carcinomas (normal versus adenomas, p<0.01; adenomas versus carcinomas, p<0.01). MVD was 25.8+/-5.4(2) in carcinomas confined to mucosa, and 36.1+/-9.6(24) in carcinomas with transmural invasion. The higher MIB-1 score was in carcinomas the more MVD increased but there was no statistical significance (r=0.38, p=0.055). MVD of carcinomas was not associated with nodal metastasis, p53 expression, and DNA ploidy. p53 protein and MIB-1 expression are useful methods for the evaluation of malignancy, and tumor angiogenesis is an early event in a colorectal tumor but MVD does not correlate with prognostic parameters except for the tumor depth.

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