Journal of Pathology and Translational Medicine

Volume 38(6); December 2004

Original Articles

Differential Expression of Promyelocytic Leukemia Protein in Autoimmune Liver Diseases.: Hyun Jung Kim, Jung Sun Kim, Yong Sang Lee, Young Hwa Chung, Han Joo Lee, Dong Jin Suh, Chong Jai Kim, Eunsil Yu; Korean J Pathol. 2004;38(6):357-363.

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Abstract PDF: BACKGROUND
Promyelocytic leukemia protein (PML) is a primary biliary cirrhosis (PBC)-specific autoantigen. Anti-PML antibody is analyzed using cultured cells with patient sera, however, PML expression has rarely been examined in liver tissues.
METHODS
In the present study, PML expression was examined immunohistochemically in paraffin embedded liver needle biopsy specimens obtained from 20 cases of PBC, 10 cases of autoimmune cholangitis, 36 cases of autoimmune hepatitis and from 5 cases of noninflammatory livers.
RESULTS
Variable PML immunopositivity was detected in the bile duct epithelial cells of 18 (90.0%) of 20 PBC cases and in all 10 cases (100.0%) of autoimmune cholangitis, whereas it was only present in 6 (16.7%) of 36 cases of autoimmune hepatitis (p<0.001). In contrast, hepatocyte PML immunopositivity was higher in autoimmune hepatitis (33/36 cases, 90.8%), than in PBC (10/20 cases, 50.0%) or autoimmune cholangitis (3/10 cases, 30.0%) (p<0.05).
CONCLUSION
Our data indicate that the differential expression of PML is closely related to autoimmune liver diseases type, and suggest that the overexpression of PML protein in bile duct cells is associated with the development of autoantibodies in patients with PBC or autoimmune cholangitis. Furthermore, PML immunoreactivity may be useful for the diagnosis of autoimmune cholangitis and overlap syndrome.

Correlation Between Neuronal Apoptosis and Expression of Inducible Nitric Oxide Synthase after Transient Focal Cerebral Ischemia.: Byoung Yuk Yi, Sung Kyoo Hwang, Ku Seong Kang, Hong Hua Quan, Young Mi Lee, Jung Wan Kim, Eun Kyoung Kwak, Ji Young Park, Yoon Kyung Sohn; Korean J Pathol. 2004;38(6):364-371.

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Abstract PDF: BACKGROUND
Neuronal death in acute-phase cerebral ischemic injury is caused by necrosis. However, neuronal injury after reperfusion can be associated with apoptosis.
METHODS
We used Sprague-Dawley rats whose brains were reperfused after middle cerebral artery occlusion for either 30 min or 2 h. We examined a relationship between apoptosis and the expression of inducible nitric oxide synthase (iNOS) in the brain tissue from 3 h to 14 days after reperfusion in both groups.
RESULTS
TUNEL and iNOS positivity were closely related in both groups. The 2-h ischemia group exhibited increases in the amount of TUNEL and iNOS-positive cells for up to 3 days after reperfusion, at which the TUNEL and iNOS-positive cells decreased. The 30-min ischemia group exhibited peak positivity 24 h after reperfusion, followed by a similar decrease. iNOS mRNA expression peaked 3 h after reperfusion in the 30-min ischemia group, at which time it decreased. In the 2-h ischemia group, iNOS mRNA increased 3 h after reperfusion, peaked 24 h after reperfusion, and then decreased.
CONCLUSION
These results indicated the occurrence of delayed apoptosis in transient cerebral ischemia. Increased expression of iNOS is closely associated with this apoptosis, and oxygen free radical-producing materials, such as nitric oxide, may play an important role in the induction of this apoptosis.

Expression of Melanoma Antigen Gene (MAGE) and Synovial Sarcoma on X chromosome (SSX) in Ovarian Tumors.: Young Ok Kim, Jean Kyung Park, Kwang Hui Kim, Jong Wook Park, Chang Ho Cheon, Won Kim, Hee Kyung Chang; Korean J Pathol. 2004;38(6):372-377.

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Abstract PDF: BACKGROUND
Several cancer-testis antigen genes or gene families have been isolated to date, including Melanoma Antigen Gene (MAGE) and Synovial Sarcoma on X chromosome (SSX). This study attempted to investigate the possibility of immunotherapy for ovarian cancer and to explore the prevalence of the expression of MAGE and SSX.
METHODS
The fresh tissue samples were obtained from 5 cases of normal ovaries, 6 cases of non-neoplastic disease, 21 cases of benign ovarian tumors, and 12 cases of malignant ovarian tumors. The expression of MAGE A1-6 and SSX 1-9 was detected by nested reverse transcriptionpolymerase chain reaction using each common primers sets for MAGE A1-6 and SSX 1-9.
RESULTS
The expression rate of MAGE 1-6 mRNA was 23.0% (5/21) for the benign ovarian tumors and 91.7% (11/12) for the malignant ovarian tumor, whereas the normal ovaries (0/5) and non-neoplastic ovarian tissues (0/6) did not express MAGE (p<0.05). The expression rate of SSX was 40.0% (2/5) for the normal ovaries, 23.0% (5/21) for the benign ovarian tumors, and 33.3% (4/12) for the malignant ovarian tumors, while the non-neoplastic ovarian tissues showed no expression of SSX (p>0.05). A relationship between the two genes was not observed (kappa coefficient=0.32).
CONCLUSION
These results suggest that the gene products of MAGE and SSX can be useful for the immunotherapy of ovarian cancer patients and that MAGE can be a more promising target than SSX from the viewpoint of applicability and cancer-specificity.

Effect of Probucol and Verapamil on Injury to Myocardium and Nerve Fibers in Rat Heart Induced by Doxorubicin.: Sang Yeop Yi, Sang Ho Cho, Woo Ick Yang; Korean J Pathol. 2004;38(6):378-387.

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Abstract PDF: BACKGROUND
Doxorubicin is considered to be one of the most effective drugs to treat a variety of human cancers. However, the dose-dependent cardiotoxicity of doxorubicin limits its clinical usefulness. This study aimed to evaluate the effect of probucol and verapamil on the cardiac neurotoxicity and cardiomyopathy induced by the long-term use of doxorubicin.
METHODS
Sprague-Dawley male rats were grouped as the control group, the doxorubicin treated group, the doxorubicin treated with probucol group, and the doxorubicin treated with verapamil group. The rats were treated for 4, 6, 8 and 10 weeks. H&E staining and immunohistochemical staining for protein gene product 9.5, caspase-3, heat shock protein 70, and hsp 25 were performed.
RESULTS
The degree of interstitial inflammatory cell infiltration was mildest in the probucol treated group. The reduction in the number of nerve fibers in the probucol treated group was less than the other treatment groups. There was a negative correlation between the treatment duration and stained nerve fibers in all the treatment groups. The number of caspase-3 positive cells was more increased in the doxorubicin group and the verapamil treated group than in the control and probucol treated group.
CONCLUSION
It is suggested that probucol partly contributed to the inhibition of doxorubicin-induced cardiac neurotoxicity and cardiomyopathy, whereas the verapamil had no effect.

CD24 Expression in Gastric Adenocarcinoma Is Associated with Tumor Invasiveness.: Kyeong Cheon Jung, Jae Nam Seo, Tae Woon Kim, Young Mi Choi, Kwon Ik Oh, Hun Ho Song, Hyung Sik Shin, Young Euy Park; Korean J Pathol. 2004;38(6):388-393.

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Abstract PDF: BACKGROUND
CD24, also referred to as the heat stable antigen in mice, is a glycosyl phosphatidylinositol- linked glycoprotein expressed by thymocytes, B cells, neutrophils and immature neuronal cells. It has been recently observed in a variety of human malignancy. Here, we demonstrated the expression of CD24 in gastric adenocarcinomas.
METHODS
A total of 40 gastric adenocarcinomas and 20 tubular adenomas were immunohistochemically examined for the expression of CD24 and matrix metalloproteinase-2 (MMP-2) proteins. The immunoreactivity of CD24 was semiquantitatively scored (0, 1+, 2+) and compared with clinicopathologic variables and MMP-2 expression in tumor cells.
RESULTS
CD24 was rarely expressed in normal gastric tissue and not expressed in tubular adenoma. In contrast, a moderate/strong expression (2+) of CD24 was observed in 25% of gastric adenocarcinomas, and 30% cases showed a weak CD24 staining (1+). Moreover, CD24 expression was significantly correlated with the depth of tumor invasion and MMP-2 expression.
CONCLUSION
These results suggest that the aberrant expression of CD24 in gastric adenocarcinomas might be associated with tumor progression and invasiveness.

Paleopathologic Analysis of a Mummified Pregnant Woman of Papyung Yoon's Family.: Woon Yong Jeong, Bong Kyung Shin, Chul Hwan Kim, Insun Kim, Woo Rim Kim, Kwang Sik Choe, Chang Sub Uhm, Juck Joon Hwang, Han Kyeom Kim; Korean J Pathol. 2004;38(6):394-400.

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Abstract PDF: BACKGROUND
A mummy is a dead body of a human being or an animal that has been preserved artificially or naturally from decaying. Because the natural environment of Korea isn't appropriate for mummification and Korean people haven't artificially made mummies, mummies were rarely studied in Korea.
METHODS
On September 6, 2002, a well-preserved female mummy was found in the grave of a family in Kyunggi-do. She was submitted to a thorough autopsy examination along with the review of genealogical documents.
RESULTS
The mummy died in winter. She was pregnant and the fetal head was observed at the vaginal orifice. The uterine wall was ruptured, and the peritoneum was discolored, probably by hemorrhage. Histologically, the gastric mucosa was well preserved. On the smear cytology of gastrointestinal material and the fluid from the coffin, pollens and parasitic eggs were observed. The woman seemed to be death from hypovolemic shock due to uterine rupture during the 2nd phase of labor.
CONCLUSION
From this case, we concluded the causes of the woman's mummification included the cold and dry circumstance at the time of her death, and the thick mortared wall of the grave that completely isolated the body from the outside.

Effect of Atorvastatin, a HMG-CoA Reductase Inhibitor, in Experimental Colitis in Mice.: Hyo Jin Park, Tae Woon Kim, Jae Nam Seo, Kwon Ik Oh, Eun Young Choi, Hyung Sik Shin, Young Euy Park; Korean J Pathol. 2004;38(6):401-407.

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Abstract PDF: BACKGROUND
The statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are approved for cholesterol reduction, and may also be beneficial in the treatment of inflammatory disease. In this study, atorvastatin was tested in experimental colitis, a disease model of inflammatory bowel disease.
METHODS
To induce colitis, dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS) were administrated to C57BL/6 or BALB/c mice. Mice were monitored daily for loss of body weight and survival for indicated days. Colon length and histology were examined after sacrifice.
RESULTS
The administration of DSS induced marked colonic inflammation and shortening, and resulted in a loss of body weight. DSSinduced colitis was not affected by atorvastatin treatment, but in contrast, the administration of atorvastatin relieved TNBS-induced colitis with a resultant rapid recovery of weight loss and a reduction in colonic length shortening. Histologically, inflammatory cell infiltration in the colonic wall, mucosal ulceration and crypt disruption were also suppressed in atorvastatin treated mice.
CONCLUSION
These results suggest that atorvastatin preserves intestinal integrity in colitis, probably via the modulation of Th cell-mediated immune response, in a manner independent of innate immunity.

The Difference of Cathepsin D Expression between Invasive Ductal Carcinoma and Ductal Carcinoma In Situ of the Breast.: Hye Kyoung Yoon, Soo Jin Jung; Korean J Pathol. 2004;38(6):408-414.

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Abstract PDF: BACKGROUND
It is known that cathepsin D expression in host stromal cells is associated with a more aggressive tumor behavior in breast cancers.
METHODS
Cathepsin D expression was examined in 222 cases of invasive ductal carcinoma (CA) and 25 cases of ductal carcinoma in situ (DCIS) by the immunohistochemical staining. Cathepsin D expression was evaluated according to the expression site, either in the tumor cells (CD-T) or in the stromal cells (CD-S), and graded according to the immunopositivity. The differences of CD-T and CD-S in each case were evaluated according to the pathologic parameters and estrogen receptor (ER)/progesterone receptor (PR) status.
RESULTS
The rate of CD-S was significantly higher in the CA than in the DCIS (p<0.0001). In the CA, the rate of CD-S was higher than that of CD-T, while in the DCIS, the rate of CD-T was higher than that of CD-S. In the CA, the rate of CD-S and the tumor grade showed a positive relationship (p=0.0281). There were positive correlations between the ER positivity and CD-S (p=0.0236), and between the PR positivity and CD-T (p=0.0246). For the DCIS, no significant relationships were noted between the pathologic parameters including ER/PR status and CD-T/CD-S.
CONCLUSION
Cathepsin D expression in the stromal cells seems to be related to the invasiveness and aggressive biological behavior in breast cancers. In addition, there might be some relationship betweeen the ER positivity and CD-S, and between the PR positivity and CD-T.

Case Reports

Giant Cystic Adenomatoid Tumor of the Uterus: A Case Report.: Mi Jin Kim, Mi Jin Gu; Korean J Pathol. 2004;38(6):415-418.

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Abstract PDF: Adenomatoid tumor of the uterus is a rare benign tumor of the uterine serosa and myometrium. It usually appears as a small nodular lesion having a distinctive histologic appearance. We describe a case of 67-year old female with a large, grossly cystic adenomatoid tumor 7x7 cm in dimension that was located at the right uterine cornus. Microscopically the tumor had unusually extensive solid proliferation of signet ring cells with large vacuoles in their cytoplasm. Also, adenoid and honeycomb-like cystic patterns were observed. The immunohistochemical and ultrastructural studies demonstrated the mesothelial origin.

Obstructive Mucocele of the Appendix Secondary to Endometriosis: A Case Report.: Chang Hun Lee, Dong Hoon Shin, Jun Woo Lee; Korean J Pathol. 2004;38(6):419-422.

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Abstract PDF: Appendiceal mucoceles are usually associated with hyperplastic or neoplastic mucosal proliferation and obstructive lesions such as postinflammatory scarring, fecalith, carcinoid tumor, and endometriosis. Among these, an association with endometriosis is known to be very exceptional. We herein report on a rare case of obstructive mucocele of the appendix that was secondary to endometriosis in a 42-year-old patient with pelvic endometriosis. A computed tomography scan demonstrated a periappendiceal abscess-like lesion with a left adnexal mass that was suggestive of endometriosis. On gross examination, the periappendiceal lesion consisted of a mucin-filled cavity (the so-called mucocele) that was 1.8 cm in diameter, and it protruded into the cecal lumen. Microscopically, the lining epithelium of the cavity was almost totally denuded. A small amount of mucus spilled over outside the mucocele, but pseudomyxoma peritonei was not present. The wall of the mucocele showed the characteristic multiple foci of endometriosis involving predominantly the muscularis propria and the serosa of the appendix and adjacent cecal walls.

Macrocystic Form of Serous Cystadenoma of the Pancreas: Two Cases Report.: Ki Seok Jang, Hyo Jin Lee, Moon Hyang Park; Korean J Pathol. 2004;38(6):423-426.

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Abstract PDF: The macrocystic form of serous cystadenoma of the pancreas is an uncommon benign neoplasm composed of few, relatively large cysts that are lined by uniform, glycogen-rich, cuboidal epithelial cells. We report here on two cases of pathologically proven macrocystic serous cystadenoma of the pancreas in a 45-year-old female patient and a 53-year-old female patient. Both these cysts were lined by low cuboidal epithelia without any evidence of mucin production. There was also no evidence of pancreatitis. These tumors were radiologically suspected as being mucinous cystic neoplasm or pseudocysts. Although the microscopic and immunohistochemical studies of the macrocystic variant are not different from the conventional serous microcystic cystadenoma, their unusual macroscopic features can lead to confusion for the clinicians and radiologists.

Paratesticular Papillary Serous Tumor of Low Malignant Potential: A Case Report.: Moon Il Park, Hun Soo Kim, Kwang Sun Suh, Dae Young Kang; Korean J Pathol. 2004;38(6):427-429.

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Abstract PDF: Paratesticular papillary serous tumors have been rarely reported, and they often resemble ovarian serous tumors of borderline malignancy. We experienced a case of papillary serous tumor in the left paratestis of a 39-year-old man. This is the second case reported in the Korean literature. The tumor, which was found incidentally during an operation for a hydrocele, was composed of papillary structures lined by cuboidal to columnar epithelial cells that displayed low cytologic atypia and frequent psammoma bodies.

Isolated Intracranial Rosai-Dorfman Disease: A Case Report.: Jin Kyu Park, Mee Yon Cho, Kwang Hwa Park, Jhin Soo Pyen; Korean J Pathol. 2004;38(6):430-433.

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Abstract PDF: Rosai-Dorfman disease (RDD) is an idiopathic histioproliferative disorder of the lymph nodes and extranodal sites. Central nervous system involvement is extremely rare. Intracranial RDD, especially the isolated form, resembles meninigioma both clinically and radiologically. Here, we report a case of isolated, intracranial, dura-based RDD. The patient presented with headache and dizziness with no evidence of lymphadenopathy. Histologically, the lesion consisted of large histiocytes with emperipolesis and lymphoplasma cell infiltrates with a fibrotic background. We discuss the differential diagnosis of this lesion. To our knowledge, this is the first reported Korean case of intracranial RDD.

Myxoma of the Ovary with Uncertain Malignant Potential: A Case Report.: Min A Kim, Ji Hoon Kim, Jae Y Ro, Geunghwan Ahn, In Ae Park; Korean J Pathol. 2004;38(6):434-437.

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Abstract PDF: Primary ovarian myxoid tumor such as myxoma, myxoid liposarcoma and myxoid leiomyosarcoma is extremely rare neoplasm. We experienced a case of unusual myxoid tumor of the ovary in a 25 year-old woman. She was admitted for an incidentally found ovarian mass during antenatal check. Radiologic studies revealed a 5.5x5 cm-sized solid mass in left ovary and she was undertaken left oophorectomy. Grossly, the round ovarian mass was measuring 8x6x5 cm, and the cut surface was predominantly solid with myxoid appearance. Microscopically, the tumor was surrounded by thick collagenous capsule and had moderate cellularity and rich vascularity. The tumor cells were stellate-shaped with abundant extracellular myxoid material without atypia. We initially thought this lesion as myxoma, but the cellularity was too high as an ordinary myxoma. Myxoid liposarcoma could also be considered as the differential diagnosis, however there was no convincing lipoblast. So, we diagnosed that tumor as myxoma with uncertain malignant potential.

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