Journal of Pathology and Translational Medicine

Volume 38(1); February 2004

Original Articles

The Effects of Ginsenoside Rb1 on the Apoptosis and the Production of Nitric Oxide in Rat C6 Glioma Cells.: Joo Hyeon Park, Yoon Hee Lee, Ku Seong Kang, Soo Kyoung Lee, Sun Zoo Kim, Ji Young Park, Eun Kyoung Kwak, Yoon Kyung Sohn; Korean J Pathol. 2004;38(1):1-7.

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Abstract PDF: BACKGROUND
Ginsenosides, the extract of Panax ginseng, exert various pharmacological effects such as anticancer activity by the mechanism that is not yet defined. In this study, we proposed that the anticancer effect of ginsenoside Rb1 is related to tumor cell apoptosis and ginsenoside Rb1 induces the tumor cell apoptosis via the nitric oxide (NO) production.
METHODS
Rat C6 glioma cells were activated by treating with lipopolysaccharide (LPS), interferon (IFN)-gamma , and tumor necrosis factor (TNF)-alpha on the culture medium to investigate the effects of ginsenoside Rb1.
RESULTS
Compared with C6 glioma cells treated with LPS/IFN-gamma/TNF-alpha, C6 glioma cells treated with LPS/IFN-gamma/TNF-alpha/ginsenoside Rb1 showed marked increase in the NO production and apoptosis. Ginsenoside Rb1 induces the NO production in C6 glioma cells in dose-dependent manner. When C6 glioma cells treated with LPS/IFN-gamma/TNF-alpha/ginsenoside Rb1 were incubated with the specific inhibitor of iNOS, S-Methyl-2-thiopseudoureasulfate (SMT), both NO production and apoptosis in C6 glioma cells was significantly decreased. Ginsenoside Rb1 induced the expression of iNOS mRNA and iNOS protein in C6 glioma cells.
CONCLUSIONS
These results suggest that the induction of iNOS expression and subsequent

Expression of CD43 in Colorectal Adenocarcinom.: Kyeong Cheon Jung, Youngmee Bae, Hyekyung Ahn, Hye Eun Kim, Myung Chul Jang, Hye Rin Roh, Gi Bong Chae, Won Jin Choi, Woo Jin Kim, Weon Seo Park; Korean J Pathol. 2004;38(1):8-14.

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Abstract PDF: BACKGROUND
CD43 is a sialoglycoprotein that is highly expressed on most leukocytes, except on B lymphocytes and dendritic cells. CD43 has been reported to be involved in the adhesion and apoptosis of lymphocytes. Although the aberrant expression of CD43 antigen in non-lymphoid tissues has been reported, the expression of the CD43 antigen in gastrointestinal malignancies is not well studied. Here, we studied the expression of CD43 in colon adenocarcinoma using the anti-CD43 monoclonal antibody developed in our laboratory.
METHODS
Thirty patients who had undergone surgical resection for colorectal carcinoma were recruited. The expression of CD43 molecule was determined by analyzing the formalin-fixed, paraffin-embedded specimens immunohistochemically using our newly developed anti-CD43 mAb (K06). The results obtained by the immunohistochemical analysis correlated to the clinicopatho-logical parameters.
RESULTS
The expression of CD43 were found in 20 out of 30 colorectal carcinoma cases. The expression of CD43 antigen is higher in well differentiated adenocarcinomas than poorly or moderately differentiated adenocarcinomas.
CONCLUSIONS
The new anti-CD43 mAb might be helpful for the detection of the expression of CD43 on colorectal carcinoma cells. Further studies are required to assess the relationship between the CD43 expression and the colorectal carcinogenesis.

Elafin Expression in Oral Lichen Planus.: Sang Shin Lee, Suk Keun Lee; Korean J Pathol. 2004;38(1):15-22.

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Abstract PDF: BACKGROUND
Elafin is a potent anti-elastase in human saliva, and is supposed to play a role in preventing oral ulceration. The expression of elafin was observed in the oral lichen planus (OLP), one of the most common noninfectious oral mucosal diseases, which frequently manifests as extensive ulceration on the involved oral mucosa.
METHODS
50 OLP, 10 oral leuko-plakia, 3 inflammatory oral ulcers, and 3 normal oral mucosa cases were fixed with 10% buffered formalin, and immunohistochemically stained with monoclonal elafin antibody. Representative specimens were fixed with 4% paraformaldehyde, and RNA in situ hybridization, with an elafin RNA probe, was performed.
RESULTS
With both the immunohistochemistry and RNA in situ hybridization the expression of elafin was more decreased in the OLP compared to the normal mucosa, while in the hyperplastic epithelium of the leukoplakia and inflammatory ulcers the expressions of elafin was more intense. In the thin epithelia of the reticular and atrophic OLPs the expressions of elafin were reduced compared to the normal mucosa, and became almost negative in the epithelium of the erosive OLP.
CONCLUSIONS
These data suggested that the extensive ulceration of the OLP was closely relevant to the reduced expression of elafin in the involved epithelium

Significance of Circumferential Resection Margin Involvement Following Esophagectomy for Esophageal Cancer.: Mee Sook Roh, Jae Ik Lee, Phil Jo Choi; Korean J Pathol. 2004;38(1):23-28.

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Abstract PDF: BACKGROUND
This study was performed to examine the significance of the circumferential resection margin (CRM) involvement by a tumor on the postoperative survival after esophageal cancer surgery.
METHODS
Fifty nine resected cases of esophageal cancers were retrospectively reviewed. The presence of a tumor either at, or within 1 mm of, the CRM was recorded. By an immunohistochemical study for Ki-67, the Ki-67 differential grades (Ki-67 DG) were defined according to the differences between the Ki-67 labeling indices of the central and of peripheral areas of the tumor nearest to the CRM: Ki-67 DG 0 (< or =10%) and Ki-67 DG 1 (>10%). The CRM involvement was correlated with the clinicopathological factors, Ki-67 DG and survival data.
RESULTS
CRM involvement was found in 26 (44.1%) of the 59 cases. There were significant differences in the cases, both with and without CRM involvement of tumor cells, in relation to lymph node metastasis, lymphovascular, perineural invasions and tumor stage (p<0.05). Ten (38.3%) of the 26 with, and 3 (9.1%) of 33 cases without, CRM involvement, showed Ki-67 DG 1 (p=0.007). The 3-year survivals of patients with and without CRM involvement were 26.8 and 61.8%, respectively (p=0.003).
CONCLUSIONS
These results show that the CRM involvement status may be used as a predictor of survival after esophageal cancer surgery, and CRM involvement is more an indicator of an advanced disease than of an incomplete resection.

Significance of p53, cyclin D1 and c-myc Expressions in Thyroid Tumors.: Zhuhu Li, Ho Jong Jeon, Mi Ja Lee; Korean J Pathol. 2004;38(1):29-34.

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Abstract PDF: BACKGROUND
The G1/S phase proteins of the cell cycle play critical roles in tumorigenesis and tumor progression. Our aim was to investigate the significance of p53, cyclin D1 and c-myc expressions in thyroid tumors.
METHODS
The expressions of these proteins were examined in 217 cases of thyroid tumors and tissues using immunohistochemistry. The results were correlated with lymph node metastasis.
RESULTS
p53 expression was seen in 75.5, 47.5, 66.7, and 50% of papillary carcinomas (PC), follicular carcinomas (FC), undifferentiated carcinomas (UC) and follicular adenomas (FA), respectively. There was a significant difference between these expressions in these tumors and the results in nodular hyperplasia (NH) and normal tissues. Cyclin D1 expression was noted in 80.0, 68.4, 66.7, 61.1 and 79.5% of PC, FC, UC, FA and NH, respectively. c-myc expression was seen in 80.0, 94.2, 66.7, 66.7 and 52.3% of PC, FC, UC, FA and NH, respectively. There was a significant association between the expressions in these tumors and the results in normal tissues. The expressions of p53, cyclin D1 and c-myc were not correlated with lymph node metastasis.
CONCLUSIONS
These findings suggest the expressions of p53, cyclin D1 and c-myc may act in the early stage, and participates in tumorigenesis and promoting cell growth.

Expression of FHIT and p21 in Gastric Adenocarcinoma.: Hyun Joo Choi, Byung Kee Kim, Jinyoung Yoo, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2004;38(1):35-41.

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Abstract PDF: BACKGROUND
The fragile histidine triad (FHIT) gene, located on the human chromosome 3p14.2, is frequently inactivated by its deletion in a number of human tumors, including gastric carcinomas. Its protein product, FHIT is presumed to have a tumor suppressor function. p21, one of the tumor markers acts as a regulator of the cell cycle, and inhibits cell proliferation.
METHODS
The association of the expressions of FHIT and p21 protein, with clinicopathological features, such as age, gender, tumor size, histological type, depth of invasion, lymph node metastasis, lymphatic and vascular invasion, grade and stage were investigated, and correlation of their expressions with p21 expression in 82 gastric adenocarcinomas attempted by immunohistochemical staining.
RESULTS
Of the 82 tumors analyzed, 58 (70.7%) were markedly reduced, or completely negative, for FHIT protein expression. The loss of FHIT expression was correlated with the depth of invasion (p=0.000), lymph node metastasis (p=0.001), lymphatic invasion (p=0.000), histological grade (p=0.000) and tumor stage (p=0.000). The loss of p21 expression was correlated with lymph node metastasis (p=0.026) and lymphatic invasion (p= 0.017), but not with the histological grade and tumor stage. The comparison of the FHIT and p21 protein expressions showed significant correlation (p=0.035).
CONCLUSIONS
The loss of FHIT and p21 expressions may be a useful indicator of the post diagnostic prognosis. Also, FHIT could be related to cell cycle arrest.

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.

Case Reports

Mesothelial Cell Inclusions Mimicking Metastatic Carcinoma in Mediastinal Lymph Node: A Case Report.: Young Min Kim, Kyu Rae Kim, Jae Y Ro; Korean J Pathol. 2004;38(1):46-49.

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Abstract PDF: The presence of benign mesothelial cell inclusions in the mediastinal lymph node is extremely rare and thus difficult for the pathologist distinguishing from sinus histiocytosis, metastatic carcinoma, or metastatic mesothelioma. We recently had a case of benign mesothelial cell inclusions in the mediastinal lymph node, which is initially misinterpreted as metastatic carcinoma of unknown origin. However, further clinical studies failed to identify the primary site. Subsequent immunostaining with calretinin demonstrated the strong nuclear and cytoplasmic immunore-activity, suggesting that these cells are mesothelial cells. It is important that when the nodal changes resemble metastatic carcinoma morphologically in the mediastinal lymph nodes, but the primary site can not be identified clinically, the possibility of mesothelial cell inclusions should be raised and the proper use of immunohistochemistry in conjunction with a clinical finding is recommended.

Osteofibrous Dysplasia-Like Adamantinoma: A Case Report with its Immunohistochemical and Ultrastructural Studies.: Na Rae Kim, Geunghwan Ahn, Geun Woo Kim, Hyun Yee Cho, Young Ha Oh, Dong Hae Chung; Korean J Pathol. 2004;38(1):50-55.

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Abstract PDF: Osteofibrous dysplasia (OFD)-like adamantinoma is a rare skeletal tumor that is characterized by the predominant OFD-like pattern with scattered epithelial nests. Adamantinoma shares clinical features (the majority of lesions in the tibia and the prevalent age group), radiologic findings (radiolucency with sclerotic shadow), and pathologic similarities (particularly the presence of scattered cytokeratin-positive stromal cells) with OFD. We describe a case of OFD-like adamantinoma. Epithelial cell nests express the epithelial membrane antigen, pancytokeratin, CK14, and collagen type IV. Ultrastructurally, the oval to spindle cells in the epithelial foci had abundant tonofilaments, and well-formed desmosomes with dense plaques, of which well preserved desmosomes are demonstrated for the first time in OFD-like adamantinoma. These immunohistochemical and ultrastructural findings further support that the origin of epithelial cells of classic and OFD-like adamantinoma are epithelial cells transformed from fibroblastic cells in the proliferating osteofibrous tissue.

Alagille Syndrome: A Case Report.: Hyosup Shim, Chanil Park, Soon Il Kim, Young Nyun Park; Korean J Pathol. 2004;38(1):56-59.

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Abstract PDF: Alagille syndrome is a rare autosomal dominant disorder showing complicated systemic manifestations, although the hepatic manifestations are predominant in many patients. We report a case of Alagille syndrome in a male baby who presented with a heart murmur at 2 days old and his echocardiography showed aortic stenosis. He presented with acholic stool and jaundice at 3 months old and a liver biopsy revealed paucity of the interlobular bile duct in the portal tract. This progressed to cirrhosis, for which a liver transplantation was performed at 10 months old. The explanted liver showed biliary-type cirrhosis with severe cholestasis. There was an absence of the interlobular bile ducts on microscopic examination. Bile duct paucity, associated with cholestasis, a peculiar face (prominent forehead, deep-set eyes, pointed mandible and bulbous nasal tip), and cardiac anomaly were observed, which were consistent with Alagille syndrome. He died of heart failure.

Squamous Cell Carcinoma Developed in Nevus Sebaceus: A Case Report.: Hyun Joo Choi, Jinyoung Yoo, Lee So Maeng, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2004;38(1):60-63.

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Abstract PDF: We report a case of squamous cell carcinoma developed within the nevus sebaceus (NS) and review the literature. An 82-year-old woman presented with a 3-month history of pain within the lifelong skin lesion on her right cheek. Examination revealed a 1.0 x 1.0 cm poorly marginated, slightly raised yellow-brown nodule. Microscopically, the skin nodule revealed the typical findings of NS. Squamous cell carcinoma developed contiguously within the keratin-filled infundibulocyst of NS disconnected from the epidermis. We suggest that squamous cell carcinoma is derived from the embryonal stratum germinativum de-differentiated from the primary epithelial germ cells in the infundibulocyst of NS. Most secondary carcinomas associated with NS grow slowly over a period of years. In contrast, squamous cell carcinoma developed in NS often grow rapidly with aggressive behavior. Thus, the accurate pathologic diagnosis is necessary.

Pseudofungi Associated with a Granulomatous Response in a Lymph Node: A Case Report.: Haeryoung Kim, Ja Seung Koo, Hyosup Shim, Gijong Yi, Sang Ho Cho; Korean J Pathol. 2004;38(1):64-67.

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Abstract PDF: . We present herein a case of pseudofungi incidentally found in the mediastinal lymph nodes of a 31-year-old woman who had a left pneumonectomy for a pulmonary blastoma. The pseudofungi were located in the subcapsular sinuses of the lymph nodes with an associated granulomatous reaction. They revealed yellowish-brown hyphae-like structures with pseudosepta and irregular branching at various angles intermingled with round yeast-like forms. These structures stained positively with periodic acid-Schiff and Gomori methenamine silver, but also stained strongly positive for Prussian blue suggesting that they contain iron. The characteristic morphological features of pseudofungi are discussed with emphasis on the features that distinguish them from true fungal organisms.

Central Core Disease: A Case Report.: Ji Hoon Kim, Young S Park, Sung Hye Park, Je G Chi; Korean J Pathol. 2004;38(1):68-71.

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Abstract PDF: Central core disease is a rare autosomal dominantly inherited non-progressive congenital myopathy, which is pathologically characterized by the formation of a "core". We report a 28-year-old female with non-progressive muscle weakness, who had a hypotonic posture at birth. The developmental milestones were delayed with her first walking at 18 months of age. She could not run or walk a long distance and weight-bearing tasks were almost impossible. None of her family members showed motor symptoms. An investigation of the electromyography and nerve conduction velocity showed non-specific results. A gastrocnemius muscle biopsy revealed central cores in approximately 70% of myofibers with a type 1 myofiber predominance and deranged sarcolemmal structures. To the best of our knowledge, this is the fifth report of central core disease in the Korean literature.

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