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Volume 32(8); August 1998
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Original Articles
Epstein-Barr Virus and p53 in Laryngeal and Nasopharyngeal Carcinomas.
Eun Sook Nam, Duck Hwan Kim, Hyung Sik Shin, Young Euy Park, Young Sik Kim, Insun Kim
Korean J Pathol. 1998;32(8):551-562.
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AbstractAbstract
To investigate the correlation between EBV infection and p53 overexpression in laryngeal carcinomas (LC) and nasopharyngeal carcinomas (NPC) in Korea, we analyzed 37 laryngeal squamous cell carcinomas and 33 nasopharyngeal (11 squamous cell and 22 undifferentiated) carcinomas. We used the immunohistochemistry and polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) for p53 overexpression and p53 gene mutation, respectively, and EBER-1 in situ hybridization and PCR using primer for EBNA-1 and EBNA-2 type 1 and 2 for prevalence and the subtype of EBV. The results were as follows; 1) The p53 expression was found in 43.2% of squamous cell LCs, in 54.6% of squamous cell NPCs and in 22.7% of undifferentiated NPCs. The p53 gene mutation was detected in 6 of 23 squamous cell LCs and 3 of 14 undifferentiated NPCs. 2) EBV was detected more frequently in undifferentiated NPCs (95.5%) than in squamous cell NPCs (63.6%) and squamous cell LCs (37.0%). Only type 1 was found in squamous cell LCs and NPCs, whereas both type 1 and type 2 were detected in undifferentiated NPCs. 3) There was no difference according to EBV infection (EBV+ ; 7 cases, EBV- ; 7 cases) in the cases with p53 protein overexpression but mutaion. From the above results, it can be concluded that squamous cell LCs and NPCs are associated with both p53 and EBV, whereas undifferentiated NPCs are more closely associated with EBV than p53. In Korea, both type 1 and 2 are detected in undifferentiated NPCs. Also, our result suggests that EBV infection does not seem to contribute to p53 overexpression. The interrelationship between EBV infection and p53 remains to be further defined.
Correlation of Heregulin mRNA and Her-2/neu Protein Expression with Node Metastasis and DNA Ploidy Pattern in Human Invasive Breast Carcinoma.
Yee Jeong Kim, Woo Hee Jung, Hyde Lee, Sung Kong Lee, In Gul Moon, Kwang Gil Lee
Korean J Pathol. 1998;32(8):563-573.
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AbstractAbstract
The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.
Correlation between Expression of p53 and Bcl-2 Protein and Epstein-Barr Virus Detection in Gastric Adenocarcinoma.
Ki Jung Yun, Weon Cheol Han, Hyung Bae Moon, Sang Woo Juhng
Korean J Pathol. 1998;32(8):574-580.
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AbstractAbstract
Epstein-Barr virus (EBV) has been known to be associated with a wide variety of neoplastic conditions including nasopharyngeal carcinoma, Hodgkin's disease, and non-Hodgkin's lymphoma. Recent studies reveal the presence of EBV in certain subtypes of gastric carcinoma in which EBV appears to be pathogenetically related. To evaluate the relationship between EBV and gastric adenocarcinoma, we examined EBV DNA using direct in situ polymerase chain reaction, and expression of p53 protein and bcl-2 protein using immunohistochemical staining method on paraffin embedded tissues. The materials consisted of one hundred twenty-eight gastric adenocarcinomas and twenty benign peptic ulcers. EBV DNA was detected in 14 of 128 gastric adenocarcinomas (10.9%). p53 protein was positive in 10 of 14 EBV positive adenocarcinomas (71.4%) and in 61 of 114 EBV negative adenocarcinomas (53.5%). Bcl-2 protein was positive in 2 of 14 EBV positive adenocarcinomas (14.3%) and in 19 of 114 EBV negative adenocarcinomas (16.7%). The above results indicate that EBV is associated with gastric adenocarcinoma, and p53 protein may play a role in carcinogenesis of EBV in gastric adenocarcinoma.
A Comparative Study of Immunohistochemical Expression of p53, bcl-2, c-erbB-2, and MIB-1 in Polypoid and Infiltrative Colorectal Carcinomas.
Jeong Seok Moon, Seong Hwan Park, Bong Kyong Shin, Ju Han Lee, Joon Ho Shin, Bom Woo Yeom
Korean J Pathol. 1998;32(8):581-589.
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AbstractAbstract
Almost all colorectal carcinomas have been thought to develop from pre-existing adenomas. However, some colorectal carcinomas can arise directly from normal flat mucosa, and usually form infiltrative mass at the early stage. The carcinogenesis of this infiltrative carcinoma may be different from the well-known adenoma-carcinoma sequence, which usually forms a polypoid mass. The purpose of this study is to investigate the different expression of various oncogenes in polypoid carcinoma and infiltrative carcinoma. We performed immunohistochemical staining on p53, bcl-2, c-erbB-2 and MIB-1 in 29 polypoid carcinomas arised from adenomas, and 21 infiltrative carcinomas. The average tumor size of infiltrative carcinomas (5.5 cm) was larger than that of polypoid carcinomas (3.1 cm), and the polypoid carcinomas were differentiated more than the infiltrative carcinomas. The results of p53, bcl-2, c-erbB-2, and MIB-1 antisera immunoreactivity in the polypoid carcinoma were 79%, 17%, 21%, and 100%, and those in the infiltrative carcinoma were 71%, 29%, 29%, and 100%, respectively. However the diffuse positivities of p53 and MIB-1 antisera were slightly higher in the infiltraive carcinomas (62%, 76%) than in the polypoid carcinomas (55%, 41%) (p=0.63, 0.01). And the results of p53 and c-erbB-2 immunoreactivity in the adenomas were 52% and 17%, respectively, which is significantly lower than that in the polypoid carcinoma(p=0.03, 0.74). The immunoreactivty of bcl-2 in the adenoma was 72%, which was significantly higher than that in the polypoid carcinoma (17%) (p<0.01). In summary, we did not show the significant difference in expression of p53, bcl-2, c-erbB-2, and MIB-1 proteins between polypoid and infiltrative carcinomas. However, the tendency of infiltrative carcinomas having a more aggressive nature suggests another carcinogenetic mechanism is involved in the colorectal carcinogenesis.
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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AbstractAbstract
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.
Expression of CD44 in Epithelial Ovarian Tumors.
Kye Weon Kwon, Hee Jeong Ahn, Yoon Jeong Choi, Hee Jae Joo, Nam Hoon Cho
Korean J Pathol. 1998;32(8):596-602.
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AbstractAbstract
CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44H) as well as several CD44 variants isoforms are produced through alternative splicing. Alternatively spliced variants of the CD44 molecule have been found to be associated with invasive and metastatic potential of cancer cells and poor prognosis in several types of carcinoma. The purpose of the present study is to define the expression of CD44H and CD44v6 in ovarian tumors and to investigate whether the expression of these molecules is associated with adverse prognosis. We evaluated the expression of CD44 isoforms in 58 ovarian tumors by means of immunohistochemistry, and correlated between CD44 expression and the histologic types, tumor grade, peritoneal implants, pseudomyxoma peritonei and FIGO stage. While the CD44H was commonly expressed in ovarian tumors, the CD44v6 was expressed in a minor proportion of serous tumors in comparison with frequent expression of v6 isoform in mucinous tumors. The CD44H expression was significantly higher in stage I/II than in stage III. However, there was no correlation between the expression of CD44 and the presence of peritoneal implants or pseudomyxoma peritonei. These results suggest that CD44H could play an important role in the adhesive function in the lower stage of the ovarian tumor and reduced expression in the higher stage might be related to the metastasis and widespread invasion of ovarian carcinoma cells.
Detection of Mycobacterium tuberculosis DNA in Ethanol-Fixed and Papanicolaou Stained Archival Materials.
Tae Sook Hwang, In Seo Park, Hye Seung Han, Jee Young Han, Young Bae Kim
Korean J Pathol. 1998;32(8):603-607.
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AbstractAbstract
Granuloma is a chronic inflammatory process associated with non-infectious agents or infectious diseases such as tuberculosis. It is well known that AFB staining, which has been used to determine the etiology of the granulomatous inflammation, lacks both sensitivity and specificity. Due to the slow growth rate of most pathogenic mycobacteria, culturing of organisms can take up to eight weeks. It is not uncommon for specific therapy to be delayed, or for an inappropriate treatment be given to patients without mycobacterial infections or with infections caused by atypical mycobacteria. Determination of the causative agent in Papanicolaou stained cytology specimens gives pathologists even more difficulties when only necrotic material has been aspirated from the center of the granuloma. In recent years, the use of a polymerase chain reaction for the amplification of DNA has appeared promising in terms of speed, efficiency, sensitivity, and specificity. Since a polymerase chain reaction permits the sensitive genetic analysis of small amounts of tissue, it is ideally suited to the genetic analysis of cytologic specimens. A polymerase chain reaction is easily performed on unfixed and unstained cells, however, an analysis of ethanol fixed and Papanicolaou-stained archival smears has also been described. We have recently established a method to detect Mycobacterium tuberculosis organism by a nested polymerase chain reaction with primers in the insertion sequence IS 6110, using cellular digests of ethanol-fixed and Papanicolaou-stained archival specimens aspirated from the lymph nodes, lungs, thyroid, etc. Inhibitors present in Papanicolaou stained material was removed by destaining the slides with 0.5% HCl solution for 10-30 minutes. Eight out of ten cases which have shown the epithelioid granulomas revealed a positive reaction and four out of ten cases which have shown lymphohistiocytic cells in a necrotic background without any evidence of granuloma revealed a positive reaction. This study showed that it was possible to employ a polymerase chain reaction to detect Mycobacterium tuberculosis in Papanicolaou stained archival cytology specimens.
Case Report
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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AbstractAbstract
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.
Original Article
Paneth Cell-rich Carcinoma of the Stomach: A case report .
Ah Won Lee, Young Shin Kim, Kyo Young Lee, Chang Suk Kang, Sang In Shim
Korean J Pathol. 1998;32(8):613-615.
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AbstractAbstract
Paneth cell-rich carcinoma is essentially an adenocarcinoma with a predominance of Paneth cells. A 60-year-old male patient was admitted with a history of abdominal distension for several months. Endoscopic examination revealed a large ulceroinfiltrative tumor involving most of the areas of the stomach. The biopsy of the lesion confirmed poorly differentiated adenocarcinoma and total gastrectomy was followed. The submitted total stomach contained a diffuse infiltrative Borrmann type IV mass with ulceration, 8.0 3.5 cm, at the body along the lesser curvature. Microscopically, it was composed of Paneth cell differentiated cancer cells and poorly differentiated tubular adenocarcinoma cells. The Paneth cell differentiation was characterized by cytoplasmic coarse eosinophilic granules, which were PAS-positive and positive reaction for lysozyme. Electron microscopic examination showed numerous, spherical, electron-dense, homogeneous granules corresponding to those in Paneth cells as well as mucin granules in the signet-ring cells, and various intermediate forms in some cancer cells, which might be immature in the Paneth cell lineage.
Case Reports
Warty Dyskeratoma with a Cutaneous Horn: Report of a case.
Ah Won Lee, Hyun Joo Choi, Youn Soo Lee, Seok Jin Kang, Byung Kee Kim, Sun Moo Kim
Korean J Pathol. 1998;32(8):616-618.
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AbstractAbstract
The clinical and pathological features of warty dyskeratoma are presented. Warty dyskeratoma is a rarely encountered, solitary, benign cutaneous tumor occurring most often on the head and neck and to our knowledge, no cases associated with cutaneous horn have been published in western literature. We experienced a case of warty dyskeratoma with a cutaneous horn occurring in a 70-year-old male, who had a 1.3 cm-sized and slowly growing nodule on his neck. A brief review of the literature, was made especially in relation to the pathological findings and histogenesis of warty dyskeratoma.
Fibroepithelial Polyp of Vagina with Atypical Stromal Cells: A case report.
Mi Ok Park, Yong Jin Kim, Jae Bok Park
Korean J Pathol. 1998;32(8):619-921.
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AbstractAbstract
A case of fibroepithelial polyp with stromal atypia in a 25-year-old female is described. The tumor arose from the vaginal wall and measured 3.5 cm in maximal diameter. It was composed of hypercellular connective tissue stroma and focal myxoid area containing numerous atypical mono- and multinucleated stromal cells. These cells may mislead to make a diagnosis of sarcoma, particulary of botryoid rhabdomyosarcoma.

JPTM : Journal of Pathology and Translational Medicine