Journal of Pathology and Translational Medicine

Volume 34(12); December 2000

Original Articles

Molecular Cloning of Novel Genes Related to the Craniofacial Development of Human Embryo.: Young Jun Lee, Tak Soo Go, Hyung Wook Han, Sang Shin Lee, Eun Cheol Kim, Yeon Sook Kim, Suk Keun Lee, Je G Chi; Korean J Pathol. 2000;34(12):961-971.

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Abstract PDF: In order to obtain novel genes for craniofacial development of human, molecular cloning and sequencing were performed and followed by in situ hybridization in tissue sections. Subtracted cDNA library of craniofacial tissue from 8 weeks old human embryo was made by the subtraction with cDNA of RHEK cells. A total of 231 clones were obtained and their partial sequence data disclosed that 214 clones were nonredundant in Genebank search. We have done in situ hybridization screening on the craniofacial sections of a 10 weeks old human fetus, and found significant positive reaction in 30 clones. Depending on the cell type of similar developmental origin, the positive reactions could be divided into four groups: first group showed an intense positive reaction in neural tube, ganglion, and a part of peripheral nerve tissue, second group relatively diffuse positive reaction in neural tube, cartilage, epithelium, and muscle, third group localized positive reaction in nerve, and muscle, and fourth group positive reaction in almost all kinds of cells of craniofacial tissues. Although every clone showed different expression patterns in the craniofacial development, some of them showed intense mRNA expressions in the characteristic cell type. Because this study also aimed to test a screening methods to find out novel genes related to craniofacial development by the subtracted cDNA library and in situ hybridization, the intense positive reaction of a certain clone by in situ hybridization may indicate its role in the developmental processes. We presumed that 30 clones selected in this study are possibly important new genes for the development of human craniofacial structure.

Expression of E-cadherin, Matrix Metalloproteinase, and Vascular Endothelial Growth Factor in Squamous Cell Carcinoma and Adenocarcinoma of the Lung.: Ji Sun Song, Mee Yon Cho, Kwang Hwa Park, Soon Hee Jung, Kwang Gil Lee; Korean J Pathol. 2000;34(12):972-981.

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Abstract PDF: E-cadherin is a calcium-dependent epithelial adhesion molecule which plays a role in the initial step of invasion of cancer cells. The step that follows the migration of separated tumor cells is a proteolytic lysis of basement membrane and extracellular matrix by protease of epithelial and endothelial cells such as matrix metalloproteinase (MMP). Vascular endothelial growth factor (VEGF) is known to be an endothelial cell-specific powerful mitogen as well as a vascular permeability factor. This study is aimed to evaluate the correlation between expression of these factors and pathologic or clinical variables and the roles and prognostic significance of those factors in squmous cell carcinoma and adenocarcinoma of the lung. Immunohistochemical stains were performed for E-cadherin, MMP-2, and VEGF in surgically resected specimens from 90 patients with squmous cell carcinoma and adenocarcinoma of the lung. Mean age of the patients was 59.7 years. Histologic type was categorized into 56 cases of squamous cell carcinoma and 34 cases of adenocarcinoma. Mean survival period of the 35 patients was 54 months. The immunohistochemical stains for E-cadherin, MMP-2, and VEGF revealed positive reaction in 67 cases (74.4%), 43 cases (47.8%), and 34 cases (37.8%), respectively. The expression of E-cadherin was higher in adenocarcinoma (82.4%) than in squamous cell carcinoma (69.6%). MMP-2 was expressed in the tumor cells, especially those invading into the surrounding stroma. The expression of MMP-2 was significantly correlated with the survival rate (p<0.05). The expression of VEGF in the tumor cells was significantly higher in cases with lymph node metastasis (p<0.05). In conclusion, these findings suggest that the expression of MMP-2 and VEGF predict poor prognosis of patients with squmous cell carcinoma and adenocarcinoma of the lung and that VEGF may play a role in tumor metastasis.

Expression of Glutathione S-Transferase, E-Cadherin, and Catenins during N,N-Diethylnitrosamine-Induced Hepatocarcinogenesis in Rat Liver.: Hyoung Joong Kim, Yon Sik Yoo, Tae Jin Lee, Mi Kyung Kim, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2000;34(12):982-993.

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Abstract PDF: N,N-Diethylnitrosamine (DEN) has been proved to have carcinogenic potential in the initiation or promotion stage and the transformed cells proliferate to form preneoplastic nodules which are positive for placental form of glutathione S-transferase (GST-P). E-Cadherin, a member of the cadherin family, is expressed in epithelial cells. To evaluate the role of adhesion molecules (E-Cadherin, alpha-catenin, and beta-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, alpha-Catenin and beta-Catenins by immunohistochemistry and immunoblotting in DEN-induced hepatocarcinogenesis of rat liver. In addition, the sequential analysis of histopathology and the expression of GST-P were also examined. Immunoreactive areas for GST-P were gradually increased from early period of carcinogenesis and strong GST-P positive foci were noted in various lesions, especially in the clear cell and eosinophilic cell nodules. Immunohistochemically, the E-Cadherin expression was increased in DEN-treated preneoplastic nodules in 4 and 10 weeks and hepatocellular carcinomas displayed relatively reduced expression compared with the hyperplastic nodules. But alpha- and beta-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of alpha-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of beta-catenin was markedly increased in 10 weeks of DEN treatment and slightly reduced in hepatocellular carcinomas. These findings suggest that during DEN-induced hepatocarcinogenesis, the clear cell and eosinophilic cell nodules expressing GST-P in their cytoplasm are early transformed cell nodules. The altered expression of E-Cadherin and catenins is closely related with tumor propagation. Loss or reduced expression of E-cadherin may play a role in the progression of late hyperplastic nodule to hepatocellular carcinoma in DEN-induced rat hepato carcinogenesis.

Glomerular Basement Membrane Thickness in Minimal Change Disease.: Yoon Mee Kim, Soon Hee Jung, Hyeon Joo Jeong; Korean J Pathol. 2000;34(12):994-1000.

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Abstract PDF: The thickness of the glomerular basement membrane may vary not only in glomerular disease, but also in normal persons according to age and sex. But there has been no data on the normal thickness of the basement membrane in Korea. This study was designed to determine the glomerular basement membrane thickness as a reference value according to age and sex, in 50 cases of minimal change disease obtained from patients aged 2~67 years. Measurement of glomerular basement membrane was made on electron micrograph using an image analyzer. The thickness of each case was estimated by the arithmetic and harmonic mean methods. The mean thickness of the glomerular basement membrane was 291.9 47.9 nm by harmonic mean method and 284.2 43.7 nm by arithmetic mean method. And the harmonic mean thickness of the glomerular basement membrane according to age was 249.1 32.5 nm (1~5 years), 256.6 45.3 nm (6~10 years), 279.2 57.9 nm (11~15 years), 303.2 43.8 nm (16~20 years), 335.3 37.5 nm (21~30 years), and 291.1 22.5 nm (over 30 years), respectively. There was a trend that the thickness of glomerular basement membranes increased with the age till 30 years of age. There was no significant sex-related difference. In conclusion, the mean glomerular basement membrane thickness is comparable to the data from western people and shows a trend of increasing thickness according to the age.

Correlation between Renal Growth Retardation and Apoptosis of Cortical Tubules in Experimentally Induced Acute Ascending Pyelonephritis in Infant Rat.: Sun Hee Sung, Soyoun Woo, Seung Joo Lee; Korean J Pathol. 2000;34(12):1001-1008.

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Abstract PDF: The infant kidney is more vulnerable to infections than the adult kidney. It is common that acute pyelonephritis (APN) during infancy and early childhood manifests growth retardation of kidney, ultimately leading to chronic renal failure. However, little is known about the pathogenesis of renal growth retardation in APN in youth. To understand the mechanism underlying the cortical lesions, urinary tract infection was induced in infant rats. To induce ascending APN, saline solution containing Escherichia coli (ATCC No. 25922) 107 bacteria/ml was infused into the bladder through the 16 gage silicone cannula in three-week-old weaning Sprague Dawley rats (weight 50~60 g, n=66). In the normal control group (n=20), saline was infused. Experimental groups were divided according to the treatment into the APN group (APN without any treatment, n=23) and TRX group (APN with ceftriaxone treatment, n=23). After performing the histopathologic examination, including inflammatory score, fibrosis score, and tubular atrophy score, we measured the apoptosis index in the tubular cells of noninflammatory cortical area at post-infection week 1 and 3 by the in situ TUNEL method. Kidney weight was significantly decreased in the APN group compared with the normal group at postinfection week 1 and 3. In the APN group, tubulointerstitial inflammation with heavy neutrophilic infiltration was found mainly in the upper and lower poles of the kidney in both the first and third week groups. Fibrosis was dominant in the third week of the APN group. However, inflammation and fibrosis were not significantly improved by TRX treatment. The apoptotic index of tubular cells was significantly increased in noninflammatory cortical area in the first week of both APN and TRX groups. It decreased near the normal control value in the third week. TGF-beta1 protein expression was localized in the inflammatory area. There was no TGF-beta1 expression in the tubules of the noninflammatory area. These findings suggest that renal growth retardation in experimentally induced APN in infant rats is related not only with the inflammatory reaction itself but also with the increased apoptosis of tubular cells in noninflammatory area. Ceftriaxone alone does not eliminate the inflammation nor prevent growth retardation effectively.

Cyclin D1 Protein Expression is Inversely Correlated with p53 Protein in Primary and Recurrent Transitional Cell Carcinoma of the Urinary Bladder.: Min Jin Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(12):1009-1015.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the urinary tract and is characterized by frequent recurrence. Like the other malignant tumor, the genetic alterations leading to neoplastic transformation of the urothelium are related with the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 is a putative protooncogene as cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumor. In this study we performed immunohistochemical stainings of cyclin D1 and p53 in both primary and recurrent transitional cell carcinomas of urinary bladder from 56 patients including 20 cases of recurrent tumor, and compared their results with histopathologic features. The results were as follows. Cyclin D1 immunoreactivity was found in 10 of 10 cases (100%) of grade 1, 25 of 41 (61%) cases of grade 2, and 11 of 25 (44%) cases of grade 3 transitional cell carcinomas. p53 immunoreactivity was found in 40% of grade 1, 63% of grade 2, and 87% of grade 3 lesions. Cyclin D1 expression was significantly higher in Ta and T1 lesions than T2 to T4 by pathologic tumor stage. Conversely p53 immunoreactivity was increased in proportion to the T classification. Cyclin D1 was de creased in recurrent transitional cell carcinomas, compared with primary transitional cell carcinomas. However, there was no statistical significance. In conclusion, cyclin D1 immunoreactivity is associated with low histologic grade and low tumor stage. And there is inverse relationship between the cyclin D1 and p53 overexpression.

SPARC Expression in Thyroid Follicular Adenomas and Carcinomas.: Chung Yeul Kim, Seong Jin Cho, Min Kyung Kim, Yang Seok Chae; Korean J Pathol. 2000;34(12):1016-1021.

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Abstract PDF: SPARC, secreted protein acidic and rich in cysteine, is a extracellular matrix-associated protein implicated in the modulation of cell adhesion, migration, cell cycle regulation, and angiogenesis. SPARC is expressed in fibrocytes and endothelial cells involved in tissue repair and invasive malignant tumors in the gastrointestinal tract, breast, lung, kidney, adrenal cortex, ovary, and brain. This study was aimed to characterize the different expression of SPARC in the thyroid follicular adenomas and follicular carcinomas. Immunohistochemical staining was performed in paraffin-embedded tissues of 25 follicular adenomas and 15 follicular carcinomas of the thyroid gland. Immunohistochemically, SPARC was not expressed in the 19 follicular adenoma and 2 follicular carcinoma but highly expressed in the 6 follicular adenoma and 13 follicular carcinoma. These findings suggest that SPARC is a potential diagnostic marker of follicular carcinoma and is helpful to distinguish follicular carcinoma from follicular adenoma without vascular or capsular invasion.

Case Reports

Mesenteric Lymphadenitis Due to Yersinia enterocolitica: A case report.: Hyang Mi Shin, Hwa Sook Jeong, Hyun Dug Wang, Young Don Lee, Ro Hyun Sung; Korean J Pathol. 2000;34(12):1022-1024.

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Abstract PDF: Mesenteric lymphadenitis due to Yersinia enterocolitica infection is not common in Korea. Although most cases of Yersinia enterocolitica-induced mesenteric adenitis are self limited, cardinal features of Yersinia enterocolitica-induced mesenteric adenitis are so similar to those of acute appendicitis that some of the patients undergo laparotomy with suspected appendicitis. The findings on laparotomy in such patients are usually enlarged mesenteric nodes with a normal or slightly inflamed appendix. Because histologic examination of the removed mesenteric lymph nodes reveals reactive hyperplasia in most cases, it is usually difficult to suspect Yersinia enterocolitica infection on morphology of the resected nodes. But suppurative granulomata of mesenteric lymph nodes, uncommonly encountered in Yersinia enterocolitica infection, strongly suggest yersinial infection. We report a case of mesenteric lymphadenitis in a 10-year-old boy, who underwent laparotomy with suspected acute appendicitis. The removed lymph node showed several suppurative granulomata in the cortex, suggesting yersinial infection. Serologic study confirmed Yersinia enterocolitica serotype O:3 infection.

Epidermoid Cyst of the Sole: A report of two cases positive for human papillomavirus.: Eun Joo Seo, Hi Jeong Kwon, Ki Ouk Min, Hyun Jeong Lee, Byung Kee Kim; Korean J Pathol. 2000;34(12):1025-1028.

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Abstract PDF: Epidermoid cysts occur rarely on the palms and soles, where hair is not present. These cysts have long been assumed to arise from traumatic implantation of epidermal fragment, but the pathogenesis is still controversial. Recently, with microscopic findings, immunohistochemical features, and molecular studies, the epidermoid cysts of the sole may be induced by the human papillomavirus. We report two cases of epidermoid cysts of the sole with the discussion of the pathogenesis.

Pineal Anlage Tumor: A case report.: Jong Sun Choi, Hyung Jin Shin, Yeon Lim Suh; Korean J Pathol. 2000;34(12):1029-1033.

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Abstract PDF: The term "pineal anlage tumor" has been recently proposed and few cases have been reported. We report the first Korean case of pineal anlage tumor in a 6-year-old girl who complained of headache and vomiting for 2 months. Brain MRI revealed a well defined, lobulated, calcifying mass in the pineal region. Tumor was totally removed. Pathological examination revealed a primitive pineal parenchymal tumor with melanotic epithelial component that was similar to histologic findings of melanotic neuroectodermal tumor of infancy, so-called retinal anlage tumor and of the developing pineal gland. The tumor was composed mostly of small, undifferentiated cells, Flexner-Wintersteiner rosettes, and ganglionic differentiation. The tumor also contained the cartilage and skeletal muscle cells.

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