Journal of Pathology and Translational Medicine

Original Articles

DPC4 Expression in the Small Intestinal Adenocarcinomas: Sun Jae Lee, Eunsil Yu, Young Kyung Bae, Kee-Taek Jang, Joon Mee Kim, Han-Ik Bae, Seung-Mo Hong, Ghil Suk Yoon; Korean J Pathol. 2012;46(5):415-422. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.415

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Background

Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis.

Methods

We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology.

Results

Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival.

Conclusions

The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.

Citations

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American Registry of Pathology Expert Opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies
Andrew M. Bellizzi, Elizabeth A. Montgomery, Jason L. Hornick
Annals of Diagnostic Pathology.2020; 44: 151419. CrossRef

Podocyte Expression of Osteopontin and FSP-1/S100A4 in Human Crescentic Glomerulonephritis.: Ghil Suk Yoon, Tae Sook Kim; Korean J Pathol. 2011;45(3):237-246.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.237

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Abstract PDF: BACKGROUND
Osteopontin (OPN) is a cytokine associated with a cell-matrix via integrins. Fibroblast specific protein-1 (FSP-1), known as S100A4, has been implicated in cell migration by non-muscle myosin. We investigated whether the role of OPN and FSP-1/S100A4 expression in their contribution to the podocyte phenotype change to form podocyte bridge and cellular crescent.
METHODS
Glomerular expression of OPN and FSP-1/S100A4 in renal biopsies of 16 patients with crescentic glomerulonephritis (CrGN) and 13 normal renal biopsies were studied by immunohistochemistry.
RESULTS
The expression of OPN and FSP-1/S100A4 was increased in the podocytes of glomeruli, with and without crescents, in patients with CrGN. Neither OPN nor FSP-1/S100A4 was expressed in glomeruli from the normal controls (p<0.01). A significant positive correlation was found between the expression of OPN in glomerular tufts and cellular crescents, and the expression of OPN and FSP-1/S100A4 in glomerular tufts (p<0.05).
CONCLUSIONS
The results suggest that OPN plays a role in early podocyte attachment to Bowman's capsule, and FSP-1/S100A4 potentiate podocyte contribution to cellular crescent formation by inducing cellular migration and growth.

Significance of Osteopontin Expression in the Progression of Human Focal Segmental Glomerulosclerosis.: Ghil Suk Yoon, Tae Sook Kim; Korean J Pathol. 2010;44(5):462-468.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.462

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Abstract PDF

BACKGROUND
Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement.
METHODS
Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry.
RESULTS
OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls.
CONCLUSIONS
The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.

Citations

Citations to this article as recorded by

Podocyte Expression of Osteopontin and FSP-1/S100A4 in Human Crescentic Glomerulonephritis
Ghil Suk Yoon, Tae Sook Kim
The Korean Journal of Pathology.2011; 45(3): 237. CrossRef

S100 Protein Positive Dendritic Cells in Liver Diseases.: Ghil Suk Yoon, Inchul Lee, Eunsil Yu; Korean J Pathol. 1998;32(8):590-595.

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Abstract: We describe S100 protein positive dendritic cells (S100+DCs) in various liver diseases including chronic viral hepatitis B and C (20 cases), liver cirrhosis (3 cases), hepatocellular carcinoma (2 cases), hepatolithiasis (6 cases), primary biliary cirrhosis (PBC) (2 cases), liver allograft rejection (9 cases), bile duct paucity (1 case), and Wilson's disease (1 case). By immunohistochemical analysis, S100+DCs were absent in fetal and normal livers, while they were variably present in inflammatory liver diseases. In chronic hepatitis and active cirrhosis, S100+DCs were most frequently located in periportal area, at lymphoid follicles within the portal tract, and at foci of spotty necrosis within the lobule. Frequency and intensity of S100+DCs were not related to etiologies of liver diseases, but they were correlated with the activity of hepatitis. In PBC, S100+DCs were found between biliary epithelial cells of the septal bile ducts, as well as, the periductal area of the portal tracts. A posttransplantation liver with features of moderate acute rejection revealed many S100+DCs in polymorphous portal infiltrates. In hepatocellular carcinomas, many S100+DCs were scattered between tumor cells. In the case of the Wilson's disease, S100+DCs were not noted. Presence of S100+DCs in various inflammatory liver diseases indicates that they play a central role as antigen presenting cells in immune responses of inflammatory liver diseases.

Case Reports

Secondary Hemochromatosis in a Patient with Aplastic Anemia: An autopsy case report.: Seung Mo Hong, Ghil Suk Yoon, Young Min Kim, Hojung Lee, Gyeong Hoon Kang, On Ja Kim; Korean J Pathol. 1998;32(8):608-612.

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Abstract: We report an autopsy case of secondary hemochromatosis associated with multiple frequent blood transfusion for the treatment of aplastic anemia. A 23-year-old man had been diagnosed as having aplastic anemia at the age of 13. He received a whole blood transfusion, about 1280 ml, every month during the past 10 years. Recently he developed diabetes mellitus and a congestive heart failure. The autopsy revealed that multiple organs were affected by secondary hemochromatosis, including the liver, heart, pancreas, spleen, bone marrow, stomach, thyroid gland, adrenal glands, and testes. The lungs and liver showed gross and microscopic findings consistent with a congestive heart failure in addition to hemochromatosis. The details are presented. This is a case of rare secondary hemochromatosis occurring in a young man and presenting the classic histopathologic changes indistinguishable from those of primary hemochromatosis.

Recurrent Viral Hepatitis Following Liver Transplantation: Report of 4 Cases.: Sunhee Chang, Kwangseon Min, Jaegul Jung, Ghil Suk Yoon, Seung Kyu Lee, Yung Sang Lee, Eunsil Yu; Korean J Pathol. 2002;36(2):122-127.

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Abstract PDF: The recurrence of viral hepatitis B or C after liver transplantation is almost universal but their clinical courses and outcomes are vary widely. We investigated four cases of rapidly progressive and fatal recurrent viral hepatitis following liver transplantation, which were rapidly progressive and fatal. Case 1 was a 58-year-old male, who developed recurrent viral hepatitisC. Case 2, 3, and 4 were a 59-year-old female, a 42-year-old male, and a 50-year-old male, respectively, who developed recurrent viral hepatitis B. In cases 1 and 2, the histopathological features of the first liver biopsies were prominent ballooning degeneration of the hepatocytes but later biopsies revealed significant lobular activity. Case 3 began with a marked fatty change and mild lobular and porto-periportal activity and progressed to severe lobular activity and septal fibrosis. In case 4, the first liver biopsy revealed minimal lobular activity but the second biopsy revealed severe lobular activity.

Original Article

Quality Improvement Methods in Cervico-vaginal Cytology: Cytologic/Histologic Correlation vs. 10% Random Rescreening .: Ghil Suk Yoon, Jooryung Huh, Kyung Hee Son, On Ja Kim, Gyungyub Gong; Korean J Cytopathol. 1998;9(2):129-138.

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Abstract PDF: Although the success of the Papanicolaou test as a screening tool of cervical cancer is evident, there still exists 2-5% of discrepancy rate by both human and machine. To improve the qualilty of cervico-vaginal cytology, the authors compared cervicovaginal smear with cervical biopsy diagnoses, and analysed the causes of discrepancies. Among 30,922 cervicovaginal smears from June 1996 to April 1997 at our hospital, there were 271 cases of cervicovaginal smear with subsequent cervical punch or LEEP cone biopsies within several months. The biopsies and smears from a total of 98 discordant cases were reviewed. The discrepancy was attributed to sampling errors in 43 cases(43.9%), and to cytologic diagnosis in 49 cases(50.0%). Among these, 43 cases were interpretative errors(categories A;19, B;16 and C;8), whereas six cases were screening errors(categories B;2 and C;4). Among cervical biopsy cases, errors were present in four. As for 10% random rescreening, cytote chnologists reviewed 3,196 of 30,922 smears during the same period. There were 43 cases of screening error(categories A;27, B;16). Cytologic/histologic correlation was superior to 10% random rescreening of negative cases. The most effective method for quality improvement in cervicovaginal cytology was to implement both quality control(rescreening) and quality assurance(cytologic/histologic correlation) programs.

Case Reports

Mucinous Adenocarcinoma in a Horseshoe Kidney.: Man Hoon Han, Sang Chul Nam, Bup Wan Kim, Ghil Suk Yoon; Korean J Pathol. 2008;42(1):60-62.

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Abstract PDF: We report here on a case of mucinous adenocarcinoma that probably originated in the renal pelvis of a horseshoe kidney. A 61-year-old woman presented with a palpable mass in the left upper quadrant of the abdomen, and this mass had been present for several months. Computed tomography (CT) revealed a left renal pelvic tumor in the horseshoe kidney. Grossly, a 10x9x8 cm unilocular cystic mass filled with chocolate colored mucinous fluid was seen. A connection between the cystic mass and the renal pelvis was demonstrated on retrograde pyelography. Microscopically, the cyst contained anaplastic columnar mucosecretory epithelial cells. Some atypical cell clusters were freely floating in the mucinous lakes. The histopathological findings were consistent with mucinous adenocarcinoma. In addition, glandular metaplasia was noted in the cystic wall. Immunohistochemical assessment of the pelvic adenocarcinoma revealed the positive expressions of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) and a weak positive expression of cytokeratin 7 (CK7).

Enterogenous Cyst of the Testis.: Sang Chul Nam, Man Hoon Han, Seok Jun Ye, Tae Gyun Kwon, Bup Wan Kim, Ghil Suk Yoon; Korean J Pathol. 2007;41(4):271-273.

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Abstract PDF: We present a rare case of an enterogenous cyst of the testis in a 21-year-old man. On ultrasonography, an ovoid hypoechoic solid mass (2x2x1.5 cm) was confined to the right testis. The left testis and bilateral epididymis were within normal limits. Grossly, the tumor was a unilocular cystic mass, without a solid component. Microscopically, the cystic mass was composed of mucin-secreting simple columnar epithelial lining cells, lamina propria and a well-differentiated muscularis propria. There was no evidence of any germ cell derivatives or neoplasia in the cystic mass and in the surrounding testicular parenchyma. Immunohistochemistry showed a positive reaction for cytokeratin and the epithelial membrane antigen in the epithelial lining; in addition, it was positive for smooth muscle actin in the well-differentiated muscularis propria.

Original Articles

Osteopontin Expression and Its Prognostic Significances in Human Renal Cell Carcinoma.: Hee Yeon Hong, Hyang Lan Lee, Tae Sook Kim, Ghil Suk Yoon; Korean J Pathol. 2006;40(3):225-230.

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Abstract PDF: BACKGROUND
Osteopontin (OPN) is a glycoprotein and it participates in cell-cell and cell-matrix interactions. In vitro studies suggest that the OPN expression is associated with tumor metastasis, and especially with the metastasis of osteotropic tumors originating in breast, prostate and lungs. Since no human tissue study has suggested the means by which OPN participates in the tumorigenesis, angiogenesis, progression and metastasis of renal cell carcinoma (RCC), we evaluated the expression and prognostic significance of OPN in RCC.
METHODS
Immunohistochemistry was performed with using the primary antibody for OPN on the archival paraffin-embedded tissue microarray specimens from 51 RCC patients who underwent radical or simple nephrectomy.
RESULTS
In the normal kidney specimens, OPN was expressed in a few compressed distal tubules adjacent to the RCCs. In RCCs, the OPN expression was elevated in larger tumors (p<0.05) and in the tumor with low microvessel density (p<0.01). In the present study, univariate analysis indicated that stage, tumor size, lymph node and distant organ metastasis are significant prognostic factors for disease free survival (DFS) in RCC patients (p<0.01), but OPN is not (p=0.0661). Multivariate analysis indicated lymph node metastasis is the independent prognostic indicator of DFS (p<0.05).
CONCLUSION
Though this study has statistical limitations, these results suggest OPN plays a role in tumor progression and metastasis and it may act as a potential prognostic indicator to predict the prognosis of RCC patients.

Effects of Genistein and Daidzein on the Growth of Human Colon Cancer HCT-116 Cells.: Jong Heon Shin, Ku Seong Kang, Joung Ok Kim, Ghil Suk Yoon, Tae Gyun Kwon, Jung Wan Kim, Yoon Kyung Sohn; Korean J Pathol. 2006;40(1):46-51.

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Abstract PDF: BACKGROUND
Genistein and daidzein are two major soybean isoflavones. They have received increasing attention because of their possible roles for cancer prevention. However, their mechanisms of action and molecular targets on the human colon cancer cells are not fully understood.
METHODS
Human colon cancer HCT-116 cells were treated with genistein and daidzein to investigate their effects on the cell growth and this was analyzed with MTT assay. TUNEL assay and Hoechst33342 stain were carried out to identify apotosis.
RESULTS
Daidzein was able to inhibit cell proliferation and induce apoptosis of the HCT-116 cells, but genistein didn't affect the cell growth. The ER antagonist ICI182780 didn't attenuate the antiproliferative and proapoptotic effects of daidzein: this means the effect of daidzein on the HCT-116 cells may not be dependent on the ER pathway. The other soybean isoflavone, genistein, attenuated the effects of daidzein on the HCT-116 cells and its mechanism should be elucidated.
CONCLUSIONS
These data suggest that daidzein may act as a preventive agent on human colon cancer, and its mechanism of action doesn't involve the ER-dependent pathway.

Expression of Heat Shock Protein 27 and Apoptosis in Renal Cell Carcinomas.: Ghil Suk Yoon; Korean J Pathol. 2006;40(1):39-45.

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Abstract PDF: BACKGROUND
Heat shock protein 27 (HSP27) is induced by heat shock and other pathophysiologic stresses, including neoplastic transformation. We examined the relationship between the HSP27 expression and the clinical and histologic parameters to elucidate the biologic and prognostic significance of HSP27 in renal cell carcinomas (RCCs). Its regulation of apoptosis in RCC development was also observed.
METHODS
We performed immunohistochemical studies for HSP27, caspase 3 and TUNEL on paraffin-embedded tissue microarray specimens from 48 RCCs.
RESULTS
There was a tendency to higher expression of HSP27 in the RCC than in normal renal tubular cells. Of the 48 RCCs, the HSP27 expression was positive in 38 cases. An inverse relationship was found between the Fuhrman nuclear grade and HSP27 expression, but this was without statistical significance (r=-0.218, p=0.093). No relationship between the HSP27 expression and the other parameters was observed. Also, no statistically significant difference was observed between apoptosis and the HSP27 expression more (p=0.951).
CONCLUSIONS
Although HSP27 expression was increased in RCC than in normal renal tubular cell the HSP27 expression may not be a powerful and statistically significant prognostic indicator in patients with RCC.

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 of CD44 Isoforms and Its Significance in Renal Cell Carcinoma.: Ghil Suk Yoon, Hee Yeon Hong, Tae Sook Kim; Korean J Pathol. 2005;39(4):251-257.

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Abstract PDF: Background
: CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.

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.

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