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Volume 34(9); September 2000
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Original Articles
Expression Pattern of DNA Mismatch Repair Genes in Tumors of Microsatellite Mutator Phenotype.
Jung Jin Kim, Myung Jin Baek, Nam Gyun Kim, Yun Hee Kim, Ji Eun Kim, Hoguen Kim, Chanil Park
Korean J Pathol. 2000;34(9):609-614.
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AbstractAbstract PDF
Microsatellite mutator phenotype (MMP) tumors were reported in a subset of gastrointestinal carcinomas. The molecular pathogenesis of MMP tumors shows defects in the DNA mismatch repair genes, and also many germline and somatic mutations were reported in the MMP tumors. However, the detection of genetic defects in the MMP tumors is very difficult, mainly because many genes are included in the DNA mismatch repair genes. This study was undertaken to determine the best strategy for detecting defects in the DNA mismatch repair genes in gastrointestinal carcinomas. One of the effective ways for detecting defects in DNA mismatch repair genes is to screen the MMP tumors and evaluate the products of DNA mismatch repair genes by performing the multiplex RT-PCR method. We have screened the MMP tumors by using 5 microsatellite markers in the 12 cancer cell lines, 120 colon carcinomas and 99 gastric carcinomas and found 6 MMP cell lines, 10 MMP colon cancers, and 9 MMP gastric carcinomas. In addition, we evaluated 6 DNA mismatch repair gene products (hMSH2, hMSH3, hMSH6, hMLH1, hPMS1 and hPMS2) by multiplex RT-PCR analysis and found decreased expression of the DNA mismatch repair genes in 5 (hMSH6 in DLD-1 and HCT-15; hMSH2 in LoVo; hMLH1 and hMSH3 in HCT-116; hMLH1 in SNU-638) out of 6 MMP cell lines. We also found a decreased expression of hMLH1 in 3 out of 10 MMP colon carcinomas, and in 6 out of 9 MMP gastric carcinomas. Our results indicate that the expression analysis of the DNA mismatch repair genes by multiplex RT-PCR method can reduce the number of genes subjected to mutational analysis and is convenient for screening the responsible DNA mismatch repair genes.
Immunohistochemical Expression of p53, E-cadherin, and nm23 Proteins in Metastatic Carcinoma of Neck Lymph Node and Corresponding Primary Carcinoma.
Jong Kook Kim, O Jun Kwon, Byung Heon Kim
Korean J Pathol. 2000;34(9):615-624.
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This study was carried out to evaluate the immunohistochemical expressions of p53, E-cadherin, and nm23 proteins in 114 cases of metastatic carcinoma of the neck lymph node (MTLNCA) and corresponding primary carcinoma (PRCA). The positive expressions of p53, E-cadherin, and nm23 proteins were 62.3%, 58.8% and 64.0%, respectively in PRCA, and 40.4%, 38.6%, and 43.9%, respectively in MTLNCA with significant down-regulation from PRCA to MTLNCA (p<0.05). The down-regulation was correlated with female gender, moderate and poor differentiation, and adenocarcinoma in p53 protein, female gender, respiratory and gastrointestinal carcinoma in E-cadherin protein, and female gender, respiratory carcinoma, moderate differentiation, and squamous cell carcinoma in nm23 protein (p<0.05). There was no significant relationship among expressions of p53, E-cadherin, and nm23 proteins (p<0.05). In conclusion, these results suggest that the expressions of p53, E-cadherin, and nm23 proteins seem to be down-regulated from PRCA to MTLNCA and this down-regulation may play a role in invasion and metastasis.
Expression of Fibronectin, Vitronectin, Surfactant-A and D in Interaction of Pneumocystis carinii and Alveolar Epithelial Cells in Pneumocystis carinii Pneumonia.
Kun Young Kwon, Young June Jeon, Eun Sook Chang
Korean J Pathol. 2000;34(9):625-635.
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Both fibronectin and vitronectin bind to Pneumocystis carinii (P. carinii) and mediate the attachment of the organisms to respiratory epithelial cells. Surfactant A and D play a role in the interaction between P. carinii and host cells. In this study we examined the expression of fibronectin, vitronectin, surfactant-A and D in the interaction between P. carinii and alveolar epithelial cells by immunohistochemistry and pre-embedding immunoelectron microscopy. The experimental rat model of P. carinii pneumonia was induced by administration of low protein diet (8%) and drinking water containing dexamethasone (2 mg/liter) for 6 to 8 weeks. The primary antibodies for light and electron microscopic immunohistochemistries were monoclonal antibodies including fibronectin (1:100) and vitronectin (1:100), and polyclonal antibodies including surfactant A (1:50) and D (1:50), respectively. Light microscopic immunohistochemistry for the fibronectin, vitronectin, surfactant-A and D showed strong expressions on the P. carinii and surface linings of type I alveolar epithelial cells. The electron microscopic immunohistochemistry of the fibronectin and vitronectin showed a strong immunoexpression along the surface pellicles and tubular extensions of P. carinii trophozoites, and surface membranes of the type I epithelial cells. The surfactant-A and D proteins showed a strong expression on the pellicles of P. carinii and surface membranes of the type I epithelial cells, but a weak expression on the free-floating surfactant materials. In conclusions, the trophozoites of P. carinii were mostly attached to type I epithelial cells. The fibronectin, vitronectin, surfactant-A and D were strongly expressed, and played an enhancing role in the binding between the P. carinii organisms and the type I alveolar epithelial cells.
Expression of CD44v6 Protein in the Progression of Colorectal Carcinomas.
Eunhee Lee, Kyoung Mee Kim, Anhi Lee, Byung Kee Kim
Korean J Pathol. 2000;34(9):636-641.
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During tumor progression, a subset of cells acquires metastatic properties, presumably through a series of genetic alterations. CD44 variant glycoproteins containing sequences encoded by exon v6 are related to tumor progression of human colorectal cancer. But their expression in normal colonic epithelium is controversial and studies of CD44 on each step of colorectal carcinogenesis are scanty. We studied CD44v6 expression in the normal colonic mucosa, adenoma, carcinoma in situ, and invasive colorectal carcinomas of different Astler-Coller stages. Endoscopically or surgically resected 36 normal colonic mucosa, 19 adenomas, 8 cases of carcinoma in situ, and 25 cases of carcinoma were selected. After immunohistochemical stain with CD44v6 antibody, positivity was graded as 0 to 4 based on the estimated percentage of positively stained tumor cells. The intensity of positive staining cells was also graded as 0 to 3. In all but one cases (97.2%), normal colorectal mucosa was negative for CD44v6. Positive rates in adenoma, carcinoma in situ, Astler-Coller stage A/B and C/D carcinoma were 73.6%, 88.9% and 87.5%, respectively. There was no statistically significant difference in the positivity between these groups. The staining intensity was significantly higher in the cases of stage C/D carcinoma group than those of adenomas (p<0.05). The percentage of positivity for CD44v6 was higher in stage C/D carcinoma group than adenoma, carcinoma in situ, and stage A/B carcinoma group (p<0.05). Expression of CD44v6 in the normal colonic mucosa was extremely rare and the positivity was increased according to the progression of colorectal tumors. Furthermore, it is more important to interpret the CD44v6 positivity according to the estimated percentage of positively stained tumor cells.
Expression of Transforming Growth Factor-beta1 in Cyclosporine-Induced Nephropathy in Rats.
Yu Na Kang, Kwan Kyu Park, Mee Yul Hwang, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Hyun Chul Kim
Korean J Pathol. 2000;34(9):642-651.
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AbstractAbstract PDF
Cyclosporine nephropathy was induced by intraperitoneal injection of cyclosporine 25 mg/kg in Sprague-Dawley rats daily for 1, 4, 8, and 12 weeks to clarify the relationship between cyclosporine nephropathy and the expression of TGF-beta1 with extracellular matrix deposition. On light microscopic examination, the kidneys in the 12 week cyclosporine-treated rats showed focal or striped fibrosis, vacuolization of tubular cells, and injury of endothelial cells. Immunohistochemically, TGF-beta1 protein was strongly expressed in the cyclosporine-treated rat kidneys, especially in the glomerular endothelial cells, interstitial endothelial cells, tubular epithelial cells, and parietal cells in the Bowman's capsule of the glomerulus as well as the periglomerular arterioles. The amount of TGF-beta1 expression was correlated with the morphological change in the cyclosporine-treated rats. Extracellular matrix, such as fibronectin and collagen IV, was also expressed in the endothelial cells of the glomerulus and the interstitium. It can be concluded, therefore that TGF-beta1 protein is probably involved in the early stage of fibrogenesis in cyclosporine nephropathy. It can be postulated that cyclosporine nephropathy results from the accumulation of extracellular matrix associated with the increase of TGF-beta1 transcription. Therefore, these results could be used in reducing fibrosis in cyclosporine nephropathy.
Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.
Yoon Jung Choi, Woo Hee Jung, Hy De Lee, Kwang Gil Lee
Korean J Pathol. 2000;34(9):652-664.
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AbstractAbstract PDF
Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.
Expression of p53 Protein and Ki-67 in Atypical Ductal Hyperplasia, Ductal Carcinoma in Situ, and Microinvasive Ductal Carcinoma of the Breast.
Yi Kyeong Chun, Hye Sun Kim, Yee Jeong Kim, Sung Ran Hong, Hy Sook Kim, Byung Jun Park, Sung Su Kang, Ji Hyun Lee, Sung Kong Lee, Sun Hee Sung, Woon Sup Han
Korean J Pathol. 2000;34(9):665-672.
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AbstractAbstract PDF
Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH). Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found. There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.
Case Reports
Complete Hydatidiform Mole with a Coexisting Fetus: A case report .
Yi Kyeong Chun, Hye Sun Kim, Yee Jeong Kim, Hy Sook Kim, Soo Kyung Choi, So Yeon Park, Sung Ran Hong
Korean J Pathol. 2000;34(9):673-676.
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AbstractAbstract PDF
Twin conceptus of a complete hydatidiform mole (CHM) and a normal fetus are rare but are important because of diagnostic difficulty, problems related to twin pregnancy, and high risk of persistent gestational trophoblastic tumor. Recently, we experienced one case of twin pregnancy consisting of a CHM and a normal fetus. A 26-year-old woman complained of vaginal bleeding. She had evidences of pregnancy-induced hypertension. A male fetus was delivered at 20 gestational weeks. The placenta demonstrated vesicles of molar change separated from normal placenta. Microscopically, the molar villi disclosed diffuse hydropic swelling with circumferential trophoblastic proliferation. DNA flow cytometric analysis showed diploid patterns in both molar and normal placental tissues. Fluorescent in situ hybridization in paraffin-embedded tissue presented that normal placental villi hybridized with X- and Y-chromosome probes (46, XY), while molar villi hybridized with X-chromosome only (46, XX). Thus, dizygotic twinning was confirmed because sex differences were shown between molar villi and normal placental villi. Follow up beta-hCG was within normal range after delivery.
Primary Osteosarcoma of the Breast: A case report.
Dong Chool Kim, Yun Kyung Lee, Ho Jong Jeon, Sung Chul Lim
Korean J Pathol. 2000;34(9):677-679.
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We report a case of primary osteosarcoma of the breast which is rare and exhibits poor prognosis. A 52 years-old-woman was admitted with rapidly growing right mammary mass. A huge lobulated dense mass with speckled calcifications, suggesting malignancy, was observed on mammography. She underwent a radical mastectomy. Grossly, the mass measured 16 14 6 cm and showed grayish white hard lobulated tissue with focal hemorrhage and necrosis. Light microscopically, the tumor was confirmed as an osteosarcoma devoid of any epithelial components. In postoperative whole body bone scan, there was no evidence of the other malignancy. To the best of our knowledge, the present case is the first report of primary osteosarcoma of the breast in Korea.
Complex Conjunctival Choristoma in Linear Nevus Sebaceous Syndrome: A case report.
Jinyoung Yoo, Jae Kyung Koh, Seok Jin Kang, Byung Kee Kim
Korean J Pathol. 2000;34(9):680-684.
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AbstractAbstract PDF
Linear nevus sebaceous syndrome is an uncommon neurocutaneous disorder characterized by nevus sebaceus, seizures, and mental retardation, and is often accompanied by ocular anormalies. We recently experienced a case of conjunctival choristoma associated with linear nevus sebaceous syndrome in a 17-month-old boy. The child was the product of a full-term uncomplicated pregnancy and normal delivery with normal karyotype of 46, XY. He was noted at birth to have a conjunctival mass on the right eye and linear nevi over the midline facial region and right temporoparietal scalp. Ophthalmologic examination revealed optic atrophy, peripapillary staphyloma, macular hypogenesis, and osseous choristoma of the choroid. A computed tomography scan demonstrated widening of the subarachnoid space and moderate atrophy of the cerebral and cerebellar hemispheres. He has been followed by ophthalmology and completely free of seizures since birth. The patient underwent excision of the conjunctival mass and biopsies of the skin lesion at 17 months of age. Histologic examination of the skin biopsies was characteristic for the linear sebaceous nevus of Jadassohn. Histologic findings of the conjunctival lesion showed a complex choristoma that contained lacrimal gland tissue and cartilage.

JPTM : Journal of Pathology and Translational Medicine