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Volume 34(5); May 2000
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Original Articles
p21 Protein Expression and Cell Proliferation Activity in Human Multistep Hepatocarcinogenesis.
Kye Weon Kwon, Young Nyun Park, Chan Il Park
Korean J Pathol. 2000;34(5):325-330.
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AbstractAbstract PDF
p21 is a universal inhibitor of cyclin-dependent kinase (cdk) and of cell-cycle progression. p21 expression is variable according to the type of tissue and the pathologic condition. To study the role of p21 in the multistep hepatocarcinogenesis, the expression of p21, p53 and Ki-67 was investigated in 53 cases of inactive liver cirrhosis, 4 cases of low grade dysplastic nodules, 3 cases of high grade dysplastic nodules, 7 cases of early hepatocellular carcinomas (HCCs), 27 cases of small HCCs (< or =3 cm), and 52 cases of advanced HCCs (>3 cm). p21 expression was not detected in liver cirrhosis, low grade dysplastic nodules, high grade dysplastic nodules and early HCCs which were mitotically inactive. p21 expression was significantly increased in small HCCs and advanced HCCs which were mitotically active. p21 expression was significantly correlated with Ki-67 labelling indices. p53 protein was not expressed in liver cirrhosis, dysplastic nodules, and early HCCs. The expression of p53 protein was, however, significantly increased in small and advanced HCCs. The p21 expression was not correlated with p53 expression. Therefore, p21 is suggested to play a role in the mitotically active small and advanced HCCs, but not in the mitotically inactive lesion of dysplastic nodules and early HCC in multistep hepatocarcinogenesis. These findings suggest that homeostatic mechanism of growth control is not totally destroyed in HCC.
Expression of Adhesion Molecules in IgA Nephropathy, Diffuse Crescentic Glomerulonephritis, and Minimal Change Disease.
Kyoung Cheol Moon, So Yeon Park, Hwal Woong Kim, Hyun Soon Lee
Korean J Pathol. 2000;34(5):331-340.
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Accumulation of leukocytes within the glomerulus is a key event in the pathogenesis of glomerulonephritis. This process is mediated by pairs of adhesion molecules. We have examined the expression pattern of selectins (E and P), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in 30 renal biopsies with IgA nephropathy, diffuse crescentic glomerulonephritis, and minimal change disease. Normal controls were obtained from four nephrectomy specimens with renal cell carcinoma. ICAM-1 expression was significantly increased in the glomerular endothelial and mesangial cells in cases with IgA nephropathy compared with normal controls. VCAM-1 was expressed in glomerular mesangial cells in all cases with IgA nephropathy and diffuse crescentic glomerulonephritis, but faintly expressed in 3 cases with minimal change disease and not expressed in normal controls. P-selectin was faintly expressed in the glomeruli in cases with IgA nephropathy and diffuse crescentic glomerulonephritis. E-selectin was only expressed in the vascular endothelium in one case with IgA nephropathy and in the other with diffuse crescentic glomerulonephritis. ICAM-1 and VCAM-1 were strongly expressed in the crescents. However, selectin was not expressed in the crescent. These results suggest that adhesion molecules, particularly ICAM-1 and VCAM-1, play an important role in the pathogenesis of glomerular damage and crescent formation in primary glomerular diseases.
Expression of p27Kip1 Protein in Carcinoma of the Urinary Bladder.
Ki Kwon Kim, Jung Ran Kim
Korean J Pathol. 2000;34(5):341-348.
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The cyclin-dependent kinase (cdk) inhibitor p27Kip1 gene is a powerful molecular determinant of cell cycle progression. Loss of expression of p27Kip1 has recently been shown to be predictive of disease progression in several human malignancies. The prognostic value and expression of p27Kip1 have been incompletely studied in bladder cancer. In this study, we investigated the relationship between p27Kip1 protein expression and clinicopathologic parameters in 50 cases of carcinoma of the urinary bladder by conducting immunohistochemical analysis and DNA flow-cytometry. Malignant bladder tissue demonstrated a heterogeneous pattern of p27Kip1 immunoreactivity. In addition, there was progressive loss of expression with increasing tumor grade. The expression of p27Kip1 protein was unrelated to stage, DNA ploidy and S phase fraction (SPF). SPF was unrelated with tumor grade and DNA ploidy. The results indicate that p27Kip1 is frequently expressed in well differentiated transitional cell carcinomas of the urinary bladder but less often expressed in muscle-invasive transitional cell carcinomas. The expression of p27Kip1 and its prevalence in low-grade tumors may reflect growth regulatory influences and potential inhibiting action in tumor progression and novel predictive markers of the biological potential of bladder tumors.
Prostatic Intraepithelial Neoplasia in Transurethral Resection Specimens On serum PSA and histologic findings.
Joon Mee Kim, Soo Kee Min, Young Chae Chu, Tae Sook Hwang, Young Bae Kim, Jee Young Han, Tae Sook Kim, Hye Seung Han
Korean J Pathol. 2000;34(5):349-357.
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Prostatic intraepithelial neoplasia (PIN), which is divided into low and high grade, has different clinicopathologic significance. We reviewed 158 prostatic tissues, which consisted of 144 cases of nodular hyperplasias and 14 cases of adenocarcinomas, to evaluate incidence of PIN, its histologic finding, and its clinical significance. Ten cases of PIN, 4 low grade and 6 high grade, were found. Four cases of low grade PIN (LPIN) and five cases of high grade PIN (HPIN) were associated with nodular hyperplasia. Only one case of HPIN occurred in carcinoma. The constant histologic findings of LPIN were nuclear stratification and nucleomegaly. The most prominent characteristics of HPIN were hyperchromasia and prominent nucleoli. Anisonucleosis was not so helpful for differential diagnosis between LPIN and HPIN. Basal layer disruption was present in one case of high grade PIN associated with adenocarcinoma, and important for the differentiatial diagnosis of cribriform HPIN from the cribriform adenocarcinoma. There was no significant difference in age incidence between the two groups with the mean age of 70.9 years in nodular hyperplasia and 69.4 years in adenocarcinoma. Serum PSA level was significantly different between the two group with the mean PSA value of 11.03 ng/ml in nodular hyperplasia and that of 73.76 ng/ml in carcinoma (p=0.000). However, PSA values between "nodular hyperplasia only" group and "PIN associated nodular hyperplasia" group were not significantly different. PIN association changed neither age distribution nor serum PSA level. During the follow up period, no adenocacinoma has occurred in the cases having PIN although serum PSA level has elevated in some cases. One case of adenocarcinoma associated with HPIN developed in the nodular hyperplasia patient. Although PIN did not increase the possibility of subsequent prostatic adenocarcinoma in transurethral resection specimens, it could not be excluded that PIN was a precursor of prostatic adenocarcinoma.
Role of HSP70 Expression in the Development of Endometrial Adenocarcinoma Correlation of ER, PR, p53, and bcl-2 protein expressions and apoptosis .
Mi Seon Kang, Seo Young Park, Sang Bo Lee, Hye Kyoung Yoon
Korean J Pathol. 2000;34(5):358-365.
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Heat shock protein of 72 kDa (HSP70) has a role in the functional modulation of sex steroid hormone receptors and in p53-associated oncogenesis and inhibits apoptosis associated with bcl-2. However, the exact role of HSP70 in the development of endometrial adenocarcinoma has not been well established. The aim of this study is to evaluate the role of HSP70 in relation with ER, PR, p53 and bcl-2 expressions and apoptosis in benign and malignant endometrial lesions. Immunohistochemical studies for HSP70, ER, PR, p53, bcl-2 and TUNEL method for apoptosis were performed in 30 cases of adenocarcinoma and 30 cases of benign endometrial lesions consisted of each 10 cases of disordered proliferative endometrium (DP), simple or complex hyperplasia (HP), and atypical hyperplasia (AH). There were no significant differences of HSP70 and bcl-2 expression rates and apoptotic index (AI) between DP, HP, AH, and adenocarcinoma. p53 expression rate in adenocarcinoma was 36.7%, but no p53 expression was identified in DP, HP and AH (p<0.05). In adenocarcinoma, HSP70 expression rate was higher in ER and PR negative adenocarcinoma (p<0.05), and p53 expression rate was higher in nonendometrioid type and FIGO grade II and III (p<0.05), but no significant difference of bcl-2 expression rate according to the histological type and FIGO grade. AI was higher in nonendometrioid type (p<0.05). There was no correlation between HSP70, p53 and bcl-2 expressions, and no significant difference of AI according to HSP70, ER, PR, p53, and bcl-2 expressions. In conclusion, higher HSP70 expression rate in poorly differentiated and ER and PR negative adenocarcinoma suggests that HSP70 inhibits ER and PR expression and may be involved in the development of poorly differentiated endometrial adenocarcinoma.
Association between the Expresson of MMP-2 and TIMP-2, and Growth Pattern of Tumor Border, Lymph Node Metastasis, and Estrogen Receptor in the Invasive Ductal Carcinoma of the Breast.
Soo Kee Min, Joon Mee Kim, Young Chae Chu, Young Up Cho, Bom Woo Yeom
Korean J Pathol. 2000;34(5):366-373.
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The most important prognostic factor of breast cancer is the status of lymph node or distant metastasis, which is resisted by basement membrane and stromal matrix. MMP (matrix metalloproteinase)-2 is a 72-kilodalton type IV collagenase/ gelatinase and degrades the type IV collagen which is a main component of the basement membrane. Therefore, MMP-2 is believed to be one of the key molecule for cancer invasion and metastasis. Enzymatic activity of MMP is inhibited by TIMPs (tissue inhibitors of metalloproteinase). TIMP-2 forms a complex with latent pro-MMP-2 and inhibits the active forms of MMP-2. The balance of MMPs and TIMPs is suspected as the important factor of invasion and metastasis of the tumor cells. We studied the association between the expression of MMP-2/TIMP-2 and growth pattern of tumor border, lymph node metastasis, and estrogen receptor expression in the 57 cases of invasive ductal carcinoma of the breast using immunohistochemical staining methods. The results revealed increased expression of MMP-2 in the infiltrating tumor border and tumors with positive lymph node metastasis and negative estrogen receptor with no statistical significance (p>0.05). But the expression of TIMP-2 was increased in expanding tumor border and tumors with positive lymph node metastasis and negative estrogen receptor without statistical significance (p>0.05).
Development of a CD-ROM Titled 'Atlas of Pathology' for Medical Students.
Dong Sug Kim, Yong Jin Kim, Sun Woo Park
Korean J Pathol. 2000;34(5):374-380.
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The authors have made a CD-ROM titled 'Atlas of Pathology (AP)' for medical students to understand histopathologic findings with ease. We used a 35 mm film scanner to convert an existing file into digital images. A pathologist and two professional programmers collaborated to create the program 'AtlasMaster 1.0' based on (IBM) PC for organization of previously captured digital images. Minimum system requirement for the 'AP' was Pentium II 166 MHz, 32 MB RAM, Windows 95 or 98, 800 600 resolution, 16-bit color, 20 speed CD-ROM drive. The 'AP' was composed of a execution file (Pathology_Atlas.exe), a DB file (pathology.mdb), and reference files (*.bmp, *.jpg, *.txt). The DB file contained fields for chapter, section, disease entity, and information for location of reference files. About 1,000 color images for various kinds of gross and microscopic pictures were stored in the CD-ROM and those were classified according to the chapters, sections, and disease entities. The 'AP' was easy to manipulate, and had advantages of self-learning for students. It could be applied to other fields in which many images were dealt with, such as histology, radiology, endoscopy, dermatology, and plastic surgery. The 'AP' was handy and very useful for medical students to study pathology and it would be a powerful self-learning tool.
Case Reports
Hepatic Veno-occlusive Disease Developed after Irradiation: A report of three cases .
Kyoungsoo Har, Se Hoon Kim, Young Nyun Park, Chanil Park
Korean J Pathol. 2000;34(5):381-385.
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Hepatic veno-occlusive disease (VOD) is a rare disease due to occlusion of the terminal hepatic venules and/or sublobular veins, which is a result of endothelial damage from pyrrolizidine alkaloids in herbal teas, irradiation of the liver, or chemotherapy particularly in association with bone marrow transplantation. We recently experienced three cases of VOD developed after radiation therapy. Two cases occurred in hepatocellular carcinoma patients of a 37-year-old man with B viral chronic hepatitis and a 22-year-old man with B viral cirrhosis and the other in a 64-year-old patient with esophageal squamous cell carcinoma. For the treatment of hepatocellular carcinoma, chemoembolization with lipiodol and adriamycin, and external irradiation on the liver mass were done. The total radiation dose was 5400 cGy and 3000 cGy in each case. Five months and 3 months after irradiation, respectively, the resected liver masses showed extensive necrosis due to pre-operative treatment. To treat esophageal carcinoma, pre-operative concurrent chemotherapy of 5-FU and radiation of 4500 cGY were done. One month after irradiation, the radical esophgectomy and wedge biopsy of the liver were done. The liver of all 3 cases showed a dark red appearance with severe congestion in contrast to the pale brown normal liver, which was not included in the radiation field. On micoscopic examination, the terminal hepatic venules and sublobular veins showed subintimal edema, fibrin deposition, and partial or total luminal occlusion by loose fibrous tissue. The centrizonal sinusoids were markedly dilatated and congested with atrophy of hepatocytes.
Non-cirrhotic Portal Hypertension in Idiopathic Myelofibrosis: A case report.
Sung Eun Kim, Young Nyun Park, Woo Ick Yang, Jin Sup Choi, Chanil Park
Korean J Pathol. 2000;34(5):386-388.
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We report a case of non-cirrhotic portal hypertension in a 73 year-old woman, who had 19-year history of idiopathic myelofibrosis. There were esophageal varix, splenomegaly, and ascites. The biopsied liver showed irregular sinusoidal/ perisinusoidal fibrosis and occasional central-to-central fibrous connection. In areas with extensive fibrosis, coarse collagen fibers filled the sinusoidal spaces and compressed hepatocytes. However, nodular regeneration was absent. Double immunohistochemical stain for smooth muscle actin and proliferation cell nuclear antigen (PCNA) revealed diffusely activated stellate cells, some of which showed nuclear PCNA staining. There was also extramedullary hematopoiesis with bizarre megakaryocytes. The portal vein and its branches were patent. Idiopathic myelofibrosis is a rare cause of non-cirrhotic portal hypertension: the portal hypertension was considered to be the result of sinusoidal/perisinusoidal fibrosis in this case.
Multiple Plexiform Schwannomas Associated with Neurofibromatosis Type 2: A case report.
Ho Sung Park, Myoung Ja Chung, Myoung Jae Kang, Dong Geun Lee, Byung Cook Ahn
Korean J Pathol. 2000;34(5):389-392.
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Plexiform schwannoma is a rare benign tumor arising from the peripheral nerve sheath and characterized by a multinodular and plexiform growth pattern. This tumor usually arises sporadically. In rare cases, plexiform schwannomas have been associated with neurofibromatosis type 2. Plexiform schwannoma should be differentiated from plexiform neurofibroma, because the latter is pathognomonic tumor of neurofibromatosis type 1 and has a potential of malignant transformation. We report a case of multiple plexiform schwannomas associated with bilateral acoustic neuromas and meningioma.

JPTM : Journal of Pathology and Translational Medicine