Journal of Pathology and Translational Medicine

Volume 36(2); April 2002

Original Articles

The Expression of Bcl-2, Bax, Cytochrome C and Caspase-3 in Camptothecin-Induced Apoptosis of Mouse 3T3 Fibroblasts.: Young Jun Ahn, Min Sup Lee, Gu Kang; Korean J Pathol. 2002;36(2):71-76.

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Abstract PDF: BACKGROUND
Camptothecin (CPT), which has been used for cancer treatment and apoptosis as an inhibitor of DNA topoisomerase I. We investigated the possibility that camptothecin induces anti-appoptotic bcl-2 and pro-apoptotic bax, cytochrome c and caspase-3.
METHODS
We performed immunocytochemical stains for bcl-2, bax and cytochrome c, and also performed westem blots for caspase-3 and the three proteins above using mouse 3T3 fibroblasts treated with CPT (0.5 microgram/mL). The immunostain for bcl-2 was done 12 hours after a microinjection of antisense oligomer to bcl-2 in the nuclei of the cells.
RESULTS
On immunocytochemistry, bcl-2 showed no expressions regardless of CPT treatment and microinjection of the antisense oligomer. The expression of cytochrome c was not changed before and after CPT treatment, and bax demonstrated weak or moderate expressions at 36 and 48 hours afte the treatment. There were no expressions at 0, 12, and 24 hours after CPT treatment. On westem blot, bcl-2 exhibited no expressions before and after CPT treatment. Expressions of ctyochrome c and caspase-3 increased after CPT treatment, and expressions of bax decreased 24 hours after CPT treatment followed by a tendency of increased expressions as time went by.
CONCLUSIONS
In the CPT-induced apoptosis of mouse 3T3 fibroblasts, CPT induced increased expressions of bax, cytochrome c and caspase-3 with no expressions of bcl-2, which are associated with the apoptosis pathway.

Ras Gene Mutations and Expression of ERK1 and ERK2 Proteins in Stomach Cancer.: Jinyoung Yoo, Seok Jin Kang, Byung Kee Kim, Chang Suk Kang; Korean J Pathol. 2002;36(2):77-83.

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Abstract PDF: BACKGROUND
We investigated stomach cancers for ras abnormalities and expression of ERK1 and ERK2 to determine their significance in the tumor development and/or progression and to evaluate their potential correlation with clinicopathologic parameters.
METHODS
Seventy gastric adenocarcinomas were studied immunohistochemically in paraffin-embedded tissue sections for the expression of ERK1 and ERK2 proteins. All tumors were further analyzed with the use of a polymerase chain reaction technique and a direct sequence analysis procedure for the presence of the mutated ras gene.
RESULTS
ERK1 and/or ERK2 was expressed in 65.7% (46/70) of the tumors; overexpression of ERK1 was observed in 38 (54.3%) tumors, whereas ERK2 was detected in 29 (41.4%). Nine (12.8%) samples demonstrated multations in the ras gene: 4 in H-ras and 5 in K-ras. Seven of the 9 (77.8%) mutated tumors were of the intestinal type. No association was established between the ras abnormalities and the overexpression of ERK1 and/or ERK2. However, the correlation between ERK2 and progression (early vs. advanced) was statistically significant (p<0.05).
CONCLUSIONS
These data indicate that ras abnormalities are uncommon events in gastric adenocarcinomas. The majority of ras mutations, however, occurred in intestinal-type tumors, supporting the notion of different molecular mechanisms involved between the intestinal-and diffuse-type lesions. Enhanced ERK2 activity may provide assistance in the determination of tumor penetration in these tumors.

The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Factor-beta1 in Unilateral Ureteral Obstruction .: Sang Mi Han, Eun Joo Kim, Hyo Soon Jeoung, Byung Yuk Lee, Sang Sook Lee, Kwan Kyu Park, Hyun Chul Kim; Korean J Pathol. 2002;36(2):84-92.

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Abstract PDF: BACKGROUND
In unilateral ureteral obstruction (UUO), the obstructed kidney is characterized by interstitial fibrosis and an increase in transforming growth factor (TGF)-beta1. Interstitial expression of TGF-beta1 is important in tublointerstitial fibrosis. The objectives of this study is to make new ribbon-type antisense oligodeoxynucleotides (ODN) for TGF-beta1 which are resistant to exonuclease and to examine the effcets of TGF-beta1 on reducing tubulointerstitial fibrosis of the kidney.
METHODS
We introduced a new ribbon-type antisense ODN for TGF-beta1 in rats using the UUO model to block interstitial fibrosis by tail vein injection. A combination of one antisense sequences for TGF-beta1 was adopted to construct a large antisense molecule with a loop and stem. Artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ)-liposomes were used as a vector system for the delivery of antisense ODN.
RESULTS
The levels of TGF-beta1 mRNA was decreased more in the cultured mesangial cells treated with ribbon-type antisense ODN than in that of a linear-type antisense ODN for TGF-beta1. TGF-beta1 mRNA was increased markedly in the interstitium of untreated obstructed kidneys. Northem analysis revealed that the levels of TGF-beta1 mRNA were decreased in the obstructed kidneys treated with antisense ODN. The fibrosis of the obstructed kidneys treated with ribbon-type antisense ODN was dramatically less than that of the untreated group.
CONCLUSIONS
These results demonstrate that the introduction of new ribbon-type antisense ODN for TGF-beta1 may be a potential therapeutic maneuver for preventing interstitial fibrosis.

Case Report

Complete Hydatidiform Mole in Early Gestation: A Clinicopathologic Study of 51 Cases.: Kyu Rae Kim, Seung Koo Lee, Sun Young Jun, So Young Park; Korean J Pathol. 2002;36(2):93-99.

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Abstract PDF: BACKGROUND
With the widespread use of high resolution ultrasound in early pergnancy periods, poorly formed diagnostic features of complete hydatidiform mole (CHM) (which mimics normal or nonmolar gestation) often lead to a confusion fo CHM with partial mole, hydropic abortion or nonmolar chromosomal abnormalities.
METHODS
We studied the clinicopathologic finnings in 51 early CHM, evacuated before 12 weeks of gestation to characterize the early histologic changes.
RESULTS
Conventional diagnostic features were not uniformly identified; extensive cavitation was identified in 51.0%, trophoblastic hyperplasia in 49.1%, and avascular villi in 13.7%. The characteristic histologic features of early CHM were cellular and basophilic stroma (82.4%), bulbous projection with linear intervening clefts (76.5%), and apoptotic stromal cells (84.3%). In 86.3%, vascularized chorionic villi showed either primitive vascular network or clearly visible vascular lumen. Nonmetastatic persistent trophoblastic neoplasia developed in 35.3% and all were cured with single-agent or combination chemotherapy. Choriocarcinoma did not develop in any cases. The extent of trophoblastic proliferation at initial curettage han no prognostic value for clinical progression to persistent hydatidiform mole.
CONCLUSIONS
The fact that the histologic features of CHM in early gestation are often not as distinctive as those in later gestation should always be kept in mind in the diagnosis of conceptual products in early gestation.

Original Articles

Allelic Loss at the BRCA1 and BRCA2 Loci in Sporadic Breast Carcinoma Using Paraffin Embedded Tissue .: Ji Young Park, Myung Hoon Lee, Dong Ja Kim, Tae In Park, Young Ha Lee, Jung Wan Kim, Yoon Kyung Sohn; Korean J Pathol. 2002;36(2):100-105.

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Abstract PDF: BACKGROUND
Germline mutations in the breast cancer-associated genes BRCA1 and BRCA2 confer susceptibility and a lifetime risk of breast. Several morphological and clinical features have been attributed to hereditary tumors. However, in sporadic breast cancer, the interrelationship between the loss of heterozygosity (LOH) of these loci and clinical features remains to be fully elucidated.
METHODS
Microdissected paraffin-embedded tissue blocks of 48 cases of surgically resected breast carcinoma were investigated to identify the LOH of BRCA1 and BRCA2 using microsatellite markers.
RESULTS
Of 48 cases, 22 (45.9%) exhibited LOH at BRCA1 locus while in 29 out of 48 (60.4%) cases LOH was observed for the BRCA2 region. There was no significant correlation between LOH at BRCA1/2 and the patient's age, tumor size, histologic grade or lymph node metastasis. When comparing the frequency of LOH with the expression of several prognostic factors, such as p53, c-erb B2 protein, estrogen and progesterone receptor using immunohistochemical stain, there was only correlation with LOH at BRCA2 and the progesterone receptor.
CONCLUSIONS
Our results suggest that allelic deletion play a role to the development of sporadic breast cancers.

Role of Angiogenesis and Expression of Vascular Endothelial Growth Factor in Mouse Skin Carcinogenesis .: Aeree Kim, Byoung Kook Kim, Hosu Chun, Ju Han Lee, Jong Sang Choi; Korean J Pathol. 2002;36(2):106-111.

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Abstract PDF: BACKGROUND
Angiogenesis is crucial for many biological processes such as embryogenesis, cyclic changes in the endometrium and wound healing. It is also critical for the growth, invasion and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) acts as a mitogen for endothelial cells and is expressed by the presence of various tumor cells. The objective of this study is to evaluate if angiogenesis is involved in the mouse skin carcinogenesis and if VEGF is related to angiogenesis.
METHODS
We induced premalignant and malignant lesions on mouse (BALB/c) skin using the two stage chemical carcinogenesis moedl, DMBA (7,12-dimethylbenzanthracene) initiation and TPA (tetra decanoyl-phorbol-acetate) promotion. And we analysed the microvessel densities (MVD) and expression of VEGF in various stages of premalignant and malignant lesions by immunohistochemical studies.
RESULTS
Squamous papillomas, keratoacanthoma, dermatofibroma, and squamous cell carcinomas were developed in 20 weeks. There were no differences in the incidence of benign and malignant tumors between 10-week and 20-week promotion groups. There were significant increases in MVD from normal and hyperplastic skin through premalignant lesion to invasive squamous cell carcinoma (p<0.0005). But the degree of VEGF expression neither correlated with neither MVD nor the tumor groups.
CONCLUSIONS
Increased angiogenesis begins from the hyperplastic stage. VEGF produced by tumor cells may not play major roles in the angiogenesis in the two stage chemical carcinogenesis model of the mouse skin.

Case Reports

Fibromatosis of the Parotid Gland: A Case Report.: Dae Su Kim, Chulhwan Kim, Insun Kim; Korean J Pathol. 2002;36(2):112-114.

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Abstract PDF: A 51-year-old woman was presented with a palpable mass in the infraauricular area that had existed for 4-months. The mass from the superficial lobe of the parotid gland was 2.7 cm in the greatest dimension and was ill-defined with rubbery, homogeneous, and fibrotic appearance. Histologically, the lesion was infiltrative into the lobules of the paratid gland, and was composed of a proliferation of spindle or stellate cells with cellular and sclerotic areas. On immunohistochemistry, the cells were only positive for vimentin and focally for smooth muscle actin. Differential diagnosis from nerve sheath tumors and solitary fibrous tumors involving the parotid gland was emphasized.

Calcitonin Producing Middle Ear Carcinoid with Amyloid Deposition: A Case Report.: Beom Jin Lim, Woo Ick Yang, Soon Won Hong, Chanil Park; Korean J Pathol. 2002;36(2):115-118.

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Abstract PDF: Carcinoid tumor of the middle ear cavity is a rare neoplasm of low malignant potential. It grows slowly and rarely metastasizes. We recently experienced a case of carcinoid tumor of the middle ear cavity occurring in a 51-year-old female who was presented with hearing loss and tinnitus of the right ear. A 1 cm sized pinkish soft mass was noted in the promontory of the middle ear. Histologically, the mass was composed of nests and cords of tumor cells with slightly pleomorphic nuclei and eosinophilic cytoplasm. The extracellular matrix was glassy pink, homogeneous and exhibited apple green birefringence under a polarized light microscope after Congo red staining. The tumor cells showed immunoreactivity for cytokeratin, chromogranin A, synaptophysin, neuron-specific enolase and calcitonin. Electron microscopic examination confirmed the presence of neurosecretory granules. The production of calcitonin and amyloid by the tumor cells suggests the possible relationship of this tumor to the thyroid C cells.

Pneumatosis Cystoides Intestinalis of Adult Ileum: A Case Report.: Seoung Wan Chae, Hye Kyung Ahn, Jin Hee Sohn; Korean J Pathol. 2002;36(2):119-121.

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Abstract PDF: Pneumatosis cystoides intestinalis is an uncommon condition characterized by the presence of multiple gas-filled cysts within the gastrointestinal wall. This lesion occurs in association with a large variety of gastrointestinal and non-gastrointestinal conditions. Herein, we describe a case of pneumatosis cystoides intestinalis of the small intestine that developed in a 31-year-old man with a history of duodenal ulcer and pyloric stenosis. Emergency exploro-laparotomy was done due to a suspicion of ulcer perforation. Primary closure for duodenal ulcer perforation and segmental resection of ileum were done. Resected ileum showed diffuse sponge-like changes in the wall. Microscopically, variable-sized cystic lesions, lined by flat or multinucleated giant cells, were noted throughout the intestinal wall.

Recurrent Viral Hepatitis Following Liver Transplantation: Report of 4 Cases.: Sunhee Chang, Kwangseon Min, Jaegul Jung, Ghil Suk Yoon, Seung Kyu Lee, Yung Sang Lee, Eunsil Yu; Korean J Pathol. 2002;36(2):122-127.

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Abstract PDF: The recurrence of viral hepatitis B or C after liver transplantation is almost universal but their clinical courses and outcomes are vary widely. We investigated four cases of rapidly progressive and fatal recurrent viral hepatitis following liver transplantation, which were rapidly progressive and fatal. Case 1 was a 58-year-old male, who developed recurrent viral hepatitisC. Case 2, 3, and 4 were a 59-year-old female, a 42-year-old male, and a 50-year-old male, respectively, who developed recurrent viral hepatitis B. In cases 1 and 2, the histopathological features of the first liver biopsies were prominent ballooning degeneration of the hepatocytes but later biopsies revealed significant lobular activity. Case 3 began with a marked fatty change and mild lobular and porto-periportal activity and progressed to severe lobular activity and septal fibrosis. In case 4, the first liver biopsy revealed minimal lobular activity but the second biopsy revealed severe lobular activity.

Alpha-Fetoprotein Producing Sertoli-Leydig Cell Tumor of the Ovary: A Case Report.: Kee Taek Jang, Hye Rim Park, Duck Hwan Kim, Chang Mo Kim, Woo Seok Sohn, Hyung Sik Shin; Korean J Pathol. 2002;36(2):128-131.

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Abstract PDF: A 26-year-old woman had an ovarian Sertoli-Leydig cell tumor (SLCT) associated with an elevated level of serum alpha-fetoprotein (AFP). The tumor had a heterologous element of intestinal-type mucinous epithelium, retiform and intermediately differentiated tubules of the Sertoli cells, and AFP-producing Leydig cells. AFP was demonstrated within the Leydig cells by an immunohistochemical technique. After surgery, the serum AFP level of the patient fell to the normal range. The present case is the first documented case of AFP producing a SLCT of the ovary reported in Korea.

Meningeal Hemangiopericytoma in a Newborn: A Case Report.: Dong Sug Kim, Seong Ho Kim, Woo Mok Byun, Jeong Ok Hah; Korean J Pathol. 2002;36(2):132-135.

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Abstract PDF: Several, but not many, cases of congenital meningeal hemangiopericytoma have been described to date. Herein, a case of meningeal hemangiopericytoma in a newborn is described. The patient was a 2-week-old boy with expanded fontanelles and frequent vomiting. A 5 cm sized mass was found in the left temporo-parietal lobe, which was well circumscribed and lobulated. Histologically the tumor was compatible with anaplastic (malignant) hemangiopericytoma, which showed pleomorphic nuclei, frequent mitotic figures and extensive hemorrhagic necrosis. The tumor cells were immunoreactive for vimentin, but negative for CD34, desmin and S-100 protein. Differential diagnosis for meningeal hemangiopericytoma was discussed, and the fact that meningeal hemangiopericytoma might have occurred congenitally was emphasized.

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