Journal of Pathology and Translational Medicine

Volume 35(4); August 2001

Original Articles

Expression of Cancer-Related Genes in Epstein Barr Virus-Infected Burkitt's Lymphoma Cell Line Treated with Mitomycin C.: Woo Bom Yeom, Seol Hee Park, Min Kyung Kim, Chul Hwan Kim, In Sun Kim, Dale Lee; Korean J Pathol. 2001;35(4):271-277.

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Abstract PDF: BACKGROUND
Infection of Epstein Barr virus (EBV) into B cells drives the infected cells into the cell cycle and frequently results in lymphoblastoid cells. Mitomycin C inhibits DNA synthesis of epithelial cells as well as lymphoid cells by cross-linking with DNA. Many of the cancer cells have various pathways for escaping the responsiveness to the negative growth-regulatory effects of mitomycin C and gaining the immortalized property. The auther performed a cell culture of an EBV infected Jijoye lymphoma cell line, and compared the cell cycle and cancer related genes between the mitomycin treated- and non-treated group.
METHODS
DNA and RNA were extracted from the Jijoye cells; and EBV nuclear antigen (EBNA)-1, 2 and latent membrane protein (LMP) of EBV and p53 and p21 mRNA analyse was performed.
RESULTS
Mitomycin C blocked G2/M phase, however, mitomycin did not affect the expression of EBNA-1, 2 and LMP. Mitomycin C also increased the p21 mRNA expression without p53 mRNA increase.
CONCLUSIONS
Mitomycin C induces B cell apoptosis by blocking the G2/M phase and by increasing p21 mRNA independent to p53, which reveals the presence of an alternative pathway of p21 induction by mitomycin C in EBV positive lymphoma cells

Immunophenotype of Thymic Epithelial Tumors According to the New World Health Organization Classification.: Sung Hye Park, Han Seong Kim, Han Kyeom Kim, Bong Kyung Shin, Seung Mo Hong, Jae Y Ro; Korean J Pathol. 2001;35(4):278-285.

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Abstract PDF: BACKGROUND
To identify the expression patterns and usefulness of various antibodies in making diagnoses and predicting prognoses, an immunohistochemical study was performed on thymic epithelial tumors (TETs).
METHODS
Forty-two cases of TETs were reclassified according to the new World Health Organization (WHO) classifications. CD3, CD5, CD79a, CD99, pan-, high- and low-molecular weight cytokeratins, EMA, vimentin, MIB-1 (Ki67) and p53 immunostaining were carried out.
RESULTS
There were two, twelve, eight, two, thirteen and one case for type A, AB, B1, B2, B3 and C, respectively. Combined B1/B2 and B2/B3 were 2 cases each. Fourteen cases (33.3%) had myasthenia gravis. CD99 was immunoreactive mainly in cortically derived lymphocytes, while CD3 and CD5 were immunoreactive in medullary-derived lymphocytes. CD5 immunoreactivity was negative in all thymic epithelial cells, except for one case of type B3. MIB-1 indices were highly expressed in cortical lymphocytes and some thymic epithelial cells, but did not show any correlation with grades. p53 in thymic epithelial cells was expressed in 6 (46%) out of 13 cases of type B3 and one case of type C, and it was negative in all other subtypes.
CONCLUSIONS
Only p53 was helpful for predicting high grades (B3 and C) (P<0.05). By MIB-1 indices, we could tell how many cortical immature lymphocytes were occupied in TETs, however, grading could not be achieved.

Caspase 3 and Ki-67 Immunoreactivity and Its Correlation with Frequency of Apoptosis in Gastric Adenomas and Carcinomas.: Jin Hee Sohn, Seoung Wan Chae, Kyung Chan Choi, Hyung Sik Shin; Korean J Pathol. 2001;35(4):286-290.

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Abstract PDF: BACKGROUND
Apoptosis, also known as programmed cell death, is under genetic control and is mediated by apoptosis-specific genes, certain oncogenes and tumor suppressor genes. Caspase 3, a group of cystein proteases, is involved in the induction of apoptosis and has been considered to be correlated with apoptosis. Therefore, we tried to define whether caspase 3 is expressed in gastric adenoma and carcinoma, and correlated with apoptosis.
METHODS
The apoptotic index and caspase 3 and Ki-67 immunoreactivity were observed in 25 gastric adenomas, 31 early gastric carcinomas (EGC) and 64 advanced gastric carcinomas (AGC) by in situ labelling and immunohistochemistry. RESULTS: The mean number of apoptotic bodies and caspase 3 immunoreactivity were significantly increased from adenoma through EGC to AGC. Ki-67 immunoreactivity was more increased in AGC than in adenoma and EGC. And the number of apoptotic bodies were positively correlated with caspase 3 and Ki-67 immunoreactivity, and caspase 3 immunoreactivity was negatively correlated with Ki-67 immunoreactivity even though they were statistically insignificant.
CONCLUSIONS
Our results suggest that caspase 3 activation is important for inducing apoptosis, and both caspase 3 and apoptosis are increased along the tumor progression.

K-ras Gene Mutations and Expression of K-ras, p16, Cyclin D1 and p53 in Synchronous Lesions of The Colon Adenoma-Carcinoma Sequences.: Hwa Eun Oh, Seong Jin Cho, Nam Hee Won, Dale Lee, Insun Kim, Bom Woo Yeom; Korean J Pathol. 2001;35(4):291-298.

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Abstract PDF: BACKGROUND
The colorectal adenoma-carcinoma sequence represents a well-known para-digm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence has been well investigated, the studies about tumors of different dignity co-existent in the same patient are rare. K-ras mutation is an early genetic change in colon cancer. The genes involved in the cell cycle such as cyclin D1, p16, and p53 are important in the tumorigenesis of the colon. The aims of this study were to determine K-ras gene mutation and expression of K-ras, p16, cyclin D1 and p53 in synchronous lesions of the colon adenoma-carcinoma sequences and their possible relationship with K-ras mutation.
METHODS
The materials included 45 colonic adenocarcinomas which were accompanied by adenoma (22 low grade and 26 high grade). By using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), we detected K-ras mutation of codon 12. An aberrant K-ras, p16, cyclin D1 and p53 expressions were stained using an immunohistochemical method. RESULTS: K-ras mutation was 52.4% (11/21) of high grade adenomas. K-ras expression was 65.4% (17/26) of high grade adenomas. p16 and cyclin D1 expressions were 50% (11/22) and 90.9% (20/22) of low grade adenomas, respectively. p53 expression was 75.6% (34/45) of adenocarcinomas. There were statistical correlations among K-ras, p16 and cyclin D1.
CONCLUSIONS
These results indicate that the ras gene mutation is an early event and the overexpressions of p16, cyclin D1 and p53 are associated with K-ras mutation and expression in adenoma-carcinoma sequences.

In Situ Detection of mRNA and RNA Component of Human Telomerase in Proliferative Lesions of the Stomach.: Mi Sook Kim, Sang Woo Juhng; Korean J Pathol. 2001;35(4):299-305.

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Abstract PDF: BACKGROUND
Proliferative lesions of the stomach were investigated by in situ hybridization using RNA probes for telomerase components and compared with the results by TRAP (telomeric repeat amplification protocol) assay.
METHODS
RNA probes for hTR (human telomerase RNA component) and hTERT (mRNA coding for a catalytic subunit of human telomerase) were made by cloning and in vitro transcription. The probes were applied for in situ hybridization in 23 cases of adenocarcinoma of the intestinal type and adjacent dysplasia, and in the normal and metaplastic mucosa of the stomach.
RESULTS
Telomerase activity by TRAP was positive in all cases of adenocarcinoma, most cases of dysplasia, and many cases of normal mucosa. hTR in situ hybridization showed positive staining in the adenocarcinoma cells, dysplastic cells, a few cells in the proliferation zone of the normal mucosa, and a few infiltrated lymphocytes. hTERT showed positive staining in the same cells.
CONCLUSIONS
Telomerase is expressed in most cases of dysplastic lesions and is thought to be acquired in the early steps of carcinogenesis. The expression is noted in a few cells of the normal proliferative zones and the infiltrated lymphocytes, emphasizing the importance of in situ detection of telomerase at the cell level.

Mast Cells in 10-Dimethyl-1,2 Benzanthracene (DMBA)-Induced Rat Mammary Carcinomas: Relationship with Matrix Metallproteinase (MMP)-2 and MMP-9 Expression.: Hyun Ho Lee, Ae Ree Kim, Bum Woo Yeom, Insun Kim; Korean J Pathol. 2001;35(4):306-313.

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Abstract PDF: BACKGROUND
It has been suggested that mast cells are involved in the tumor growth and progression by production of a variety of enzymes and growth factors. They were studied in the 10-dimethyl-1,2 benzanthracene (DMBA)-induced rat mammary tumors, and evaluated in relation with the production of tryptase, chymase, and matrix metalloproteinase (MMP)-2 and MMP-9.
METHODS
Preneoplastic and neoplastic breast tissues of Sprague-Dawley female rats were obtained every week after DMBA treatment for 12 weeks. Toluidine blue stain was used for the identification of mast cells. Mast cell tryptase was studied by immunohistochemistry, and chymase by esterase stain. MMP-2 and MMP-9 were measured by Western blotting.
RESULTS
The numbers of mast cells in breast cancers were higher than in preneoplastic tissues, and there was a positive correlation between the numbers of tryptase-positive cells and the tumor size. MMP-9 quantity was correlated with the numbers of toluidine blue and chymase positive cells, but not with tryptase-positive cells and tumor size. Both active and inactive forms of MMP-2 and MMP-9 were identified in zymogram.
CONCLUSIONS
The mast cells are increased in the DMBA-induced breast cancers, and their tryptase and chymase may play a role in tumor progression with or without participation of MMP-2 and MMP-9.

Preferential Expression of CD44 in Thyroid Papillary Carcinoma.: jung Yeon Kim, Jinye Yoo, Hyejae Cho; Korean J Pathol. 2001;35(4):314-318.

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Abstract PDF: BACKGROUND
Papillary carcinoma is one of the most common malignant thyroid tumors and an important prognostic factor is the lymph node status. CD44 is a cell adhesion molecule and is associated with metastasis. The purpose of this study was to discover whether CD44 is valuable in the diagnosis of the papillary carcinoma, and whether Ki-67 and p53 are correlated with CD44 in the papillary carcinoma.
METHODS
We studied CD44, Ki-67 and p53 expressions in 34 cases of formalin-fixed paraffin embedded papillary thyroid carcinomas, and 20 cases of the follicular neoplasm using mouse anti-CD44 (H-CAM), Ki-67 and p53 monoclonal antibodies. RESULTS: Most of the papillary carcinomas expressed diffuse and intense membrane staining of CD44 (32/34 cases, 94.1%). Focal scattered immunoreactivity was observed in the follicular neoplasm (8/20 cases, 40.0%). The staining patterns of CD44 were similar in both follicular adenoma and carcinoma. Both groups with or without lymph node metastasis showed similar expression patterns for CD44. There were no differences in Ki-67 and p53 staining between papillary carcinomas and follicular neoplasms.
CONCLUSIONS
The result shows that papillary carcinomas preferentially display the CD44 antigen, and it is a useful diagnostic tool in the equivocal cases. There is no correlation among CD44, Ki-67 and p53 expressions in the papillary carcinoma.

Expression of Matrix Metalloproteinase (MMP)-1, MMP-3 Nitrotyrosine and Apoptosis in Articular Cartilage of Human Osteoarthritis.: So Young Jin, Seong Su Kang, Dong Wha Lee, Soo Jae Yim, Yeo Hon Yun, Byung Ill Lee; Korean J Pathol. 2001;35(4):319-329.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase (MMP)-1 and 3 are the most important degradating enzymes of the chondroid matrix. Chondrocytes may undergo apoptosis under various stimuli including nitric oxide (NO). We studied the expression rate and zone of MMP-1, MMP-3, nitrotyrosine, a marker of NO release, and apoptosis in the articular cartilage of human osteoarthritis.
METHODS
To investigate the role of nitrotyrosine and apoptosis in the degradation of the chondroid matrix in human osteoarthritis, immunohistochemistry was done for MMP-1, MMP-3, and nitrotyrosine; and the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method was performed for apoptosis using a total of 93 articular cartilages from 12 femoral heads and 17 knees obtained from total joint arthroplasty and 7 normal articular cartilages. RESULTS: In the normal control group, the expression rates for MMP-1, MMP-3, nitrotyrosine, and apoptosis were very low; and their expression zones were confined to the superficial layer of the articular cartilage. Their expression rates were low in the early stage of osteoarthritis and were moderate to high in the late stage (P<0.05). Their expression zones were confined to the superficial layer of the articular cartilage in the early stage of osteoarthritis and were expressed throughout the whole layer in the late stage and those of MMP-3 and nitrotyrosine were statistically significant (P<0.05). Their expression rates and zones were significantly correlated with the grade of osteoarthritis (P<0.05). Conclusion : The expression rate and zone of apoptosis and nitrotyrosine correlated well with those of MMP-1 and MMP-3. Therefore, NO and apoptosis may be related to the progression of human osteoarthritis.

Loss of Heterozygosity on Chromosome 9p21, 17p13 and 3p in Human Astrocytic Tumor.: Youn Soo Lee, Chang Suk Kang, Seung Myung Dong, Jung Yong Lee, Sang In Shim, Byung Kee Kim; Korean J Pathol. 2001;35(4):330-337.

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Abstract PDF: BACKGROUND
The purpose of this study was to determine the genetic abnormalities of chromosomes 9p21, 17p13.1, 3p25 and 3p14.2 in the development and progression of astrocytic tumors.
METHODS
We performed loss of heterozygosity (LOH) analysis in 41 astrocytic tumors, including 20 astrocytomas, 11 anaplastic astrocytomas and 10 glioblastomas, and correlated the results of LOH at different histopathologic grades. LOH was determined by multiplex polymerase chain reaction analysis of the DNA, which was extracted by microdissection.
RESULTS
LOH of 9p21 was found in 55.6% of astrocytomas, 54.6% of anaplastic astrocytomas and 100.0% of glioblastomas. LOH of 17p13.1 was found in 21.4% of astrocytomas, 28.6% of anaplastic astrocytomas, and 66.7% of glioblastomas. LOH of 3p25 was found in 37.5% of astrocytomas, 16.7% of anaplastic astrocytomas, and 14.3% of glioblastomas. LOH of 3p14.2 was found in 16.7% of astrocytomas, 40.0% of anaplastic astrocytomas, and 42.9% of glioblastomas. LOH on chromosome 9p21 and 17p13.1 was closely related with the histopathologic grades.
CONCLUSIONS
These results may suggest that LOH of 9p21, 17p13.1, 3p25 and 3p14.2 involves an early event of astrocytoma development and accumulates during progression. LOH of 3p25 may be involved in the tumorigenesis of astrocytoma. Identification of these LOH may illuminate the stepwise pathogenesis of astrocytic tumors and predict the possibility of malignant transformation.

Development of the Pathology Laboratory Teaching Material Composed of Digital Pictures and Presentation over the Internet.: Sang Yeop Yi; Korean J Pathol. 2001;35(4):338-343.

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Abstract PDF: BACKGROUND
To maximize the efficiency of the pathology laboratory class, it has been realized that students should be given an environment with repeated learning situations. For this purpose, this study was designed to present the significance that pathologists need in order to publish teaching materials over the Internet.
METHODS
The pictures were captured as different magnified digital data from teaching glass slides. To modify the images, a graphics program was used, and these were transferred to the Microsoft PowerPoint software and developed as final teaching material. The final teaching material was then published on the Internet. This material can be browsed by searching through windows and by the indices of diagnosis. RESULTS: The comments from all users of the teaching material used in this study showed that it was user-friendly and appropriate for searching and reviewing. The users could assess information easily before and after the laboratory sessions. The quality of the images in this material was appropriate for printing. All users from our university were satisfied with the fact that all pictures were captured from their own teaching slides.
Conclusions
: Therefore, the teaching material used in this study is helpful for medical students studying pathology. Furthermore, this trial may induce others to develop pathology teaching materials over the Internet.

Case Report

Isolated Polypoid Ganglioneuroma in the Rectum.: Se Hoon Kim, Chang Hwan Choi, Yong Han Paik, Won Ho Kim, Hoguen Kim; Korean J Pathol. 2001;35(4):344-346.

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Abstract PDF: Gastrointestinal ganglioneuroma is a rare benign neoplasm, composed of ganglion cells, nerve fibers, and supporting cells. Ganglioneuromas are presented as isolated polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromas. We have experienced a case of an isolated ganglioneuromatous polyp in the rectum. The patient was a 58-year-old female who had experienced low abdominal discomfort and tenesmus for 6 to 7 months. Colonoscopic examination revealed a polypoid tumor in the rectum. Microscopically, the tumor showed cystic glands, expanded lamina propria, and smooth surface epithelium. Many proliferated ganglion cells with nerve fibers were evident in the lamina propria which was extended to the submucosa.

Original Article

Primary Extragastrointestinal Stromal Tumor (EGIST) of the Greater Omentum.: Kyung Un Choi, Jee Yeun Kim, Do Youn Park, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Jun Woo Lee; Korean J Pathol. 2001;35(4):347-350.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g. The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields. Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.

Case Reports

Adenoid Basal Carcinoma of the Uterine Cervix.: Youn Kyung Lee, Ho Jong Jeon, Keun Hong Kee; Korean J Pathol. 2001;35(4):351-353.

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Abstract PDF: We report a case of adenoid basal carcinoma of the uterine cervix unexpectedly found in a 68-year-old female. She was diagnosed with a high-grade squamous intraepithelial lesion (HSIL) on a cervical smear and subsequent cervical punch biopsy. Total abdominal hysterectomy was performed, and there were no significant gross findings in the uterine cervix. Microscopically, the epithelial surface showed a HSIL with glandular extension. Below the neoplastic epithelial lesion were numerous small nests of uniform small cells, which extended to the parametrium. These tumor cells contained hyperchromatic nuclei, inconspicuous nucleoli, and scant cytoplasm. Peripheral palisading and gland-like or acinar structures in the nests were noted. The latter were positive for mucicarmine stain. Foci of squamous differentiation exhibiting occasional mitoses and large atypical cells were seen in the small nests. Stromal reaction was not obvious. Immunohistochemically, the HSIL lesion and adenoid basal carcinoma lesion were negative for human papillowa virus. The tumor cells forming nests were positive for carcinoembryonic antigen, S-100 protein, and high molecular weight cytokeratin, but were negative for -smooth muscle actin and chromogranin A.

A Case of Solitary Cutaneous Myofibroma of the Thigh in An Adult.: Jung Hwan Park, Chang Woo Lee, Young Chae Chu, Moon Hyang Park; Korean J Pathol. 2001;35(4):354-356.

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Abstract PDF: Adult solitary cutaneous myofibroma is a recently described benign neoplasm of the skin or subcutis, representing the adult counterpart of infantile myofibroblastoma. The histologic and immunohistochemical features of a 21-year-old woman with a solitary brownish, mildly tender nodule on her right thigh are reported here. The nodule had been present for a duration of 3 years. It showed a nodular dermal mass with an irregular margin. The lesion consisted of interlacing bundles of spindle cells which were positive for smooth muscle actin, muscle specific actin and vimentin. Immunohistochemical stainings for desmin, S-100 protein, CD 34 and CD 68 were negative. Cutaneous myofibroma in an adult is a distinct entity of benign neoplasm.

Medullomyoblastoma with Neuronal and Rhabdomyoblastic Differentiation.: Tae Woong Noh, Tai Seung Kim; Korean J Pathol. 2001;35(4):357-360.

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Abstract PDF: Medullomyoblastoma is a very rare central nervous system tumor and is regarded to be a variant of medulloblastoma showing a rhabdomyoblastic component. We found 32 cases of medullomyoblastoma in English literature. We recently experienced a case of a cerebellar medullomyoblastoma with neuronal differentiation in a 15-year-old girl who displayed headaches and vomiting. The tumor displayed extensive neuronal and myoblastic differentiation on microscopic and immunohistochemical examination. On ultrastructural study, the tumor obviously demonstrated rhabdomyoblastic features showing myofilaments composed of actin and myosin with well developed Z-bands.

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