Journal of Pathology and Translational Medicine

Volume 31(9); September 1997

Original Articles

The Effect of Ginseng Saponin on the Dopaminergic Neurons in the Parkinson's Disease Model in Mice.: Chang Ok Kim, Ki Sok Kim, Young Buhm Huh, Byeong Woo Ahn, Beom Seok Han, Kwang Sik Choi, Ki Yul Nam, Sang Woo Juhng; Korean J Pathol. 1997;31(9):805-814.

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Abstract PDF: Saponin has been known to be a major antioxidant component in panax ginseng. Recent experimental study suggests that some antioxidant materials prevent Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in an animal model. The present study was performed to demonstrate the effect of ginseng saponins in the Parkinson's disease model induced by MPTP. To verify the effect of ginseng saponin on dopaminergic neurons in the mice brain, the tyrosine hydroxylase-immunoreactive (TH-ir) neurons were observed by immunohistochemical stain and immunoelectron microscopy (preembedding method). Also, in order to estimate the immunoreactivity of dopaminergic neuropils, they were quantified by image analysis. The number of TH-ir neurons of substantia nigra was significantly increased in the high-dose (0.46 mg/kg) ginseng saponin group compared with the MPTP injected group. The immunoreactivity of TH-ir neuropils in striatum was significantly increased in both high and low-dose (0.1 mg/kg) ginseng saponin groups compared with the MPTP injected group. In immunoelectron microscopic observation, TH-ir neurons of the control and both ginseng saponin injected group showed normal nuclei and well preserved cytoplasmic organelles. In the MPTP injected group, dying dopaminergic neurons showed destroyed nuclei and cytoplasmic organelles. These results suggest that ginseng saponin has a protective effect on the Parkinson's disease model induced by MPTP.

Pathologic Analysis of 71 Cases of Cerebral Cortical Dysplasia.: Sang Pyo Kim, Seung Che Cho; Korean J Pathol. 1997;31(9):815-822.

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Abstract PDF: Cortical dysplasia (CD) is considered to be a malformative lesion of the neocortex which exhibits a spectrum of pathologic changes reflecting a disturbance in the process of its development. CD is recently recognized as a major cause of intractable epilepsy with non-neoplastic lesions. Mischel et al. proposed that CD can be graded mild, moderate and severe with regard to nine specific microscopic abnormalities: mild CD consists of 1) cortical laminar disorganization, 2) single heterotopic white matter neurons, 3) neurons in the cortical molecular layer, 4) persistent remnants of the subpial granular cell layer, and 5) marginal glioneuronal heterotopia; moderate CD displays 6) polymicrogyria and 7) white matter neuronal heterotopia; severe CD phows 8) neuronal cytomegaly with associated cytoskeletal abnormalities and 9) balloon cell change. We reassessed 71 cases of cortical dysplasia to elucidate the proportion and histologic features of each group, using Mischel's grading system. CD was most frequently found in the temporal lobe with 50 cases (70%). Mild CD was predominently seen and was noted in 61 cases (86%) Cortical laminar disorganization and single heterotopic white matter neurons were identified in all mild CD cases. Neurons in the cortical molecular layer, persistent subpial granular cell layer, and marginal glioneuronal heterotopia were also noted in case numbers 40, 3, and 1 of mild CD, respectively. Moderate CD was composed of 2 cases with polymicrogyria, and the remaining 8 cases had severe CD. All moderate and severe CD were associated with the various histological features of mild CD. Thirty eight cases (51%) of CD showed dual pathology, composed of both CD and hippocampal sclerosis, and 5 cases of dysembryoplastic neuroepithelial tumor also had CD. Neurofilament immunostain revealed disarray of abnormally beaded axons in CD. We believe that the grading system of CD is very important to the evaluation and classification of CD.

Immunohistochemical Study on the Expression of p53 and Bcl-2 Proteins in Non-Small Cell Lung Carcinomas.: Ok Ju Lee, Do Youn Park, Kang Suek Suh; Korean J Pathol. 1997;31(9):823-831.

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Abstract PDF: To address the possible prognostic value of p53 and Bcl-2 proteins in non-small cell lung carcinomas (NSCLCs), the authors studied 43 cases of NSCLCs diagnosed between the years 1990 to 1995 at Pusan National University Hospital. The patients were treated either by pneumonectomy or lobectomy of the lung. The expression of p53 and Bcl-2 proteins was semiquantitatively analyzed in paraffin sections by immunohistochemical method and correlated with clinicopathologic prognostic parameters of NSCLCs. Overexpression of the p53 protein was found in 31 cases (72.1%) of the 43 NSCLCs. Overexpression of the p53 protein was significantly correlated with the decreasing degree of histologic differentiation, increasing tumor stage, and cigarette smoking. Bcl-2 expression was found in 19 cases (44.2%) of the 43 NSCLCs. Increased expression of the Bcl-2 protein was significantly correlated only with decreasing tumor stage. An inverse relationship was found between p53 and Bcl-2 proteins, but it was not statistically significant. Thus p53 and Bcl-2 proteins, as demonstrated immunohistochemically in routine paraffin sections, could be of value in prediction of the aggressiveness and prognosis of NSCLCs, in agreement with the central role of p53 and Bcl-2 proteins in the evolution of NSCLCs associated with cigarette smoking.

Characteristics of the Immortalized Human B-cells by Epstein-Barr Virus.: Ho Jong Jeon, Bong Nam Choi, Yoon Kyeong Oh; Korean J Pathol. 1997;31(9):832-846.

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Abstract PDF: Human lymphoblastoid B-cell lines immortalized by Epstein-Barr virus (EBV) were established from peripheral blood of patients with acute myeloblastic and chronic lymphocytic leukemia and chronic fatigue syndrome. The sera of patients with acute myeloblastic and chronic lymphocytic leukemia did not show antibodies to Epstein-Barr viral capsid antigen (VCA), but serum of a patient with chronic fatigue syndrome disclosed antibodies to VCA (IgG, IgM), and EBNA was demonstrated in peripheral blood mononuclear cells by polymerase chain reaction. The established cell lines were mature B-cell phenotypes with polyclonal proliferation in early passage and no evidence for commitment to other lineages. The immortalized cells by EBV were designated as CSUP-1 and CSUP-2 (from acute myeloblastic leukemia, FAB classification M2 and M1), CSUP-3 (from chronic lymphocytic leukemia) and CSUP-4 (from a patient with chronic fatigue syndrome). The CSUP-1, 2, 3, and 4 grew in suspension forming clumps with a doubling time of 38 to 49 hours. Colony formation was not recognized in plate. By light and electron microscopic examination, the immortalized cells showed features of lymphoblastoid to plasmacytoid lymphocytes, and multinucleated giant cells. The lymphoblastoid cells showed scanty cytoplasm with poorly developed organelles. Immunophenotypic analyses of CUSP-1, 2, 3, and 4 with monoclonal antibodies by flow cytometry showed B-cell phenotype with polyclonal proliferation in early passage. Epstein-Barr virus nuclear antigen was confirmed in the extracted DNAs from immortalized cells by polymerase chain reaction. DNA analysis showed a normodiploid stemline with a DNA index of 1.12. The established cells were strongly reactive for CD10, CD30 (Ki-1) in early passage, and bcl-2 and c-myc onco-protein in early and late passage. Karyotypic analysis of CSUP-1, 2, 3 and 4 showed 46, XY or 46, XX. No tumorigenesis in heterotransplanted SCID mouse was recognized. This immortalized cells by EBV should be a valuable cell lines to study the pathogenesis of EBV-related malignant lymphoma.

Detection and Subtyping of Epstein-Barr Virus in Gastrointestinal Adenocarcinomas and Malignant Lymphomas.: Young Sik Kim, Seol Hee Park, In sun Kim; Korean J Pathol. 1997;31(9):847-861.

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Abstract PDF: Epstein-Barr virus (EBV) has been linked to a spectrum of neoplastic conditions, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, lymphoepithelioma-like carcinomas and malignant lymphomas in immunocompromised state. To determine the prevalence and the subtype of EBV in gatrointestinal malignancies, fifty cases of adenocarcinomas and seventeen cases of malignant lymphomas were analyzed by EBERs in situ hybridization and polymerase chain reaction using primers for EBNA-1, EBNA-2A and EBNA-2B, on the paraffin sections. In addition, immunohistochemical stain for p53 protein was performed to investigate the potential role of EBV infection on tumor suppressor gene, p53, during tumorigenesis. EBER was detected in 6 of 26 gastric adenocarcinomas, 2 of 24 colon adenocarcinomas, and 8 of 17 malignant lymphomas. EBER was more prevalent in malignant lymphoma arising in the intestine (6/6) than in the stomach (2/11), and was detected in both B and T cell phenotypes. EBNA-1 was positive in 11 of 16 EBER positive cases and the subtyping was possible in 8; both type 1 and 2 were detected in gastric cancers, whereas only type 2 was found in intestinal neoplasms. In adenocarcinomas the high rate of p53 protein overexpression was found in both EBER positive (8/8) and negative cases (32/42), whereas the positive rate was higher in EBER positive cases (7/8) than in EBER negative cases (4/9) of malignant lymphomas. From the results, it can be concluded that EBV infection and the p53 tumor suppressor gene are independently associated in a significant portion of the gastrointestinal malignancies, but the mechanism of action remains to be elucidated.

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.

A Study of the Correlation between Prognostic Factors of Human Gastric Carcinomas and the Expression of CD44.: Ho Lee, Hyung Chul Kim, Woo Sung Moon, Myoung Jae Kang; Korean J Pathol. 1997;31(9):873-883.

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Abstract PDF: This study was performed to investigate the relationship between CD44 expression and depth of, tumor invasion histopathologic differentiation, tumor size, lymph node metastasis, and proliferating capacity of tumor cells in the gastric carcinoma. In 20 cases of early gastric carcinoma (EGC) and 40 cases of advanced gastric carcinoma (AGC), the immunohistochemical staining for CD44v3, CD44v5, and PCNA gave the following results. 1) In all 60 cases, the positive rates for CD44v3 and CD44v5 were 18.3% and 71.7%, respectively. 2) CD44v5 was expressed in 45% of EGC and 85% of AGC. 3) Larger tumors exhibited higher positive rates for CD44v5. 4) There were 28 cases of lymph node metastases out of 43 cases of CD44v5- positive primary gastric carcinomas (65.1%), and there were 4 cases of lymph node metastases out of 17 CD44v5-negative cases (23.5%). 5) There was no relationship between CD44v5 expression and PCNA index. Because the tumors that exhibit deep invasion, and large in size and have lymph node metastses tend to have more frequent expression of CD44v5, CD44v5 may be one of the useful prognostic markers for gastric carcinoma.

Clonality of Large Regenerative Nodule Accompanied by Hepatocellular Carcinoma.: Zhe Piao, Bong Kyun Chun, Woo Jung Lee, Young Nyun Park, Ho guen Kim, Chanil Park; Korean J Pathol. 1997;31(9):884-890.

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Abstract PDF: In order to clarify the preneoplastic nature of large regenerative nodules without dysplastic change, we analysed the clonality of hepatocellular carcinomas (HCCs) and large nodules, diameter > or =0.5 cm, of cirrhotic liver by X-linked human androgen receptor (HUMARA) gene assay, using the principle of random X chromosome methylation and inactivation in female. Ten cases of HCC and 5 cases of large nodules without dysplasia from 9 female patients were selected. All the tumors, large nodules and paired normal control cells were selectively microdissected from deparaffinized hematoxylin and eosin stained slides. Genomic DNA was isolated and digested with HhaI. Polymerase chain reaction(PCR) amplication of the HUMARA locus was performed using 32P-a-dCTP containing PCR mixtures. The PCR amplified products were separated by gel electrophoresis and analysed by autoradiography. Nine HCCs from 8 patients were monoclonal and 1 case was polyclonal and the remaining 1 case was not polymorphic at the HUMARA locus. The HCC case which showed polyclonality contained many inflammatory cells. All the large nodules were polyclonal by HUMARA assay. These results suggest that all or most of the cells composing the large regenerative nodules without dysplasia are polyclonal. This assay may be informative for the differentiation between regenerative and preneoplastic nodules in cirrhotic liver and the size of nodule may be not important in hepatocarcinogenesis.

Case Reports

Mediastinal Hemangioma: Report of a case.: Jong Ok Kim, Bum Kyeong Kim, Kyoung Hee Kim, Dae Young Kang, Kwang Sun Suh; Korean J Pathol. 1997;31(9):891-894.

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Abstract PDF: Benign hemangioma of the mediastinum is rare. This slowly growing tumor is described as well circumscribed, cystic, hemorrhagic tumor. Histologically it can be differentiated into capillary or cavernous form. We present a case of mediastinal hemangioma. A 20-year-old-man was presented with a slowly growing posterior mediastinal mass of 6 years duration, 8x6 cm in size. The mass was relatively well defined but focally invasive. Microscopically, it was differentiated into vessels of capillary, cavernous, and venous patterns. A solid cellular proliferation with inconspicuous capillary lumens was focally seen. The stroma between variable-sized vessels showed marked myxoid change associated with some smooth muscle bundles and adipose tissue. Ultrastructurally, areas of solid cellular proliferation showed formation of lumens. These lumens were lined by active endothelial cells showing plasmalemmal vesicles and Weibel-Palade bodies on the abluminal surface.

Paraganglioma of Cauda Equina.: Seok Jin Kang, Youn Soo Lee, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1997;31(9):895-897.

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Abstract PDF: This case report describes a paraganglioma of the cauda equina in a 37-year-old man, as documented by light microscopy and immunohistochemistry. The patient experienced low back pain of 3 years duration, with the recent onset of sciatic pain and altered sensation in the right leg. Magnetic resonance imaging of L4 vertebral level revealed an ovoid, solid mass in the cauda equina. The mass was measured 1.5 cm in the greatest diameter. The histologic appearance was characterized by organoid pattern with clusters of chief cells (zellballen). Immunohistochemically, tumor cells are positive for keratin, epithelial membrane antigen, vimentin, neuron specific enolase and chromogranin.

Mucous Gland Adenoma of the Bronchus; Light Microscopic and Ultrastructural Features.: Mi Seon Kwon, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1997;31(9):898-901.

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Abstract PDF: We present a case of mucous gland adenoma arising from the main bronchus of the lower lobe of the left lung in terms of clinicopathologic, immunohistochemical, and ultrastructural aspects as well as review of related literatures. The patient, a 31-year-old female, was admitted to Catholic University Medical College Hospital with complaints of coughing and purulent sputum for about seven years. The chest CT showed a severely calcified tumor in the left lower lobe of the lung. Grossly, the calcified tumor arising from the main bronchus protruded into the lumen and showed bronchiectasis of the lower lobe and atelectasis of the upper lobe of the lung. The tumor was pale brown-gray and sharply circumscribed and showed some small cystic spaces filled with mucoid material. Microscopically, most of the tumor showed dystrophic calcification. The growth pattern of the tumor is composed of cysts, tubules, and glands lined by cytologically bland columnar, cuboidal, or flattened mucus secreting cells. Electron micrograph of tumor cells showed some round or oval mucous granules measuring 0.5-1.8 micrometer.

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