Journal of Pathology and Translational Medicine

Volume 36(1); February 2002

Original Articles

A Study of Apoptosis Induced by Microinjection of Cytochrome c Protein into Mouse 3T3 Fibroblast.: Min Sup Lee, Gu Kang; Korean J Pathol. 2002;36(1):1-6.

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Abstract PDF: BACKGROUND
Microinjectors have been used for cell biology and development, and are useful for the study of cellular morphologic changes with response to the external milieu and intracellularly injected molecules.
METHODS
This study was performed to confirm the apoptotic changes induced by intracytoplasmic microinjection of cytochrome c (5 mg/mL) to mouse 3T3 fibroblasts with and without pretreatment of Ac-DEVD-CHO (100 mol/mL), and BSA (bovine serum albumin, 5 mg/mL) as a control, and evaluate the usefulness of microinjection as a method to study apoptosis pathways.
RESULTS
Mild focal cytoplasmic fragmentation was seen in the cells microinjected with cytochrome c as early as 10 min after the injection. Apoptotic morphology with apoptotic body formation was observed at 60 min after the injection, and then new apoptotic change of the injected cells was not seen. Cytochrome c-injected cells showed about 31% of apoptotic cells of the total injected cells 50-60 min after the injection. BSA-injected cells did not show apoptosis morphology at 50-60 min after the injections. Caspase-3 inhibitor, Ac-DEVD-CHO-treated cells with cytochrome c microinjection exhibited lower apoptosis indices (average apoptosis index; 11.5+/-8.6%) than non-treated cells of the inhibitor (average apoptosis index; 11.5+/-8.6%).
CONCLUSIONS
It was observed that intracellular microinjection of cytochromic c induced apoptosis which was inhibited by Ac-DEVD-CHO, although apoptotic cells were so easily detached that further study could not be performed. However it is thought that microinjection should be a method to study apoptosis and signal transduction with the molecular biological techniques currently available.

Correlation Between Expression of p53, Bcl-2 Protein and Ki-67 Labelling Index and Lymph Node Metastasis in Early Gastric Cancer.: Joon Hyuk Choi, Young Ran Shim; Korean J Pathol. 2002;36(1):7-12.

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Abstract PDF: BACKGROUND
The purpose of this study was to investigate the difference of cliniopathological variables and p53, bcl-2, and Ki-67 labelling index between early gastric cancer with and without lymph node metastasis.
METHODS
The authors analyzed thirty patients who had early gastric cancer confined to submucosa (sm cancer) without lymph node metastasis and thirty patients who had sm cancer with lymph node metastasis. The expression of p53 protein, bcl-2 protein and Ki-67 labelling index were evaluated by immunohistochemistry.
RESULTS
No significant correlation was found between lymph node metastasis and age, sex, tumor size, Lauren classification, histologic grade, and venous invasion. But lymphatic invasion was significantly correlated to lymph node metastasis (p<0.01). The p53 positive rate was 73.3% (22/30) and 66.7% (20/30) in sm cancer with and without lymph node metastatsis, respectively. The bcl-2 positive rate was 40.0% (12/30) and 30.0% (9/30) in sm cancer with and without lymph node metastasis, respectively. The Ki-67 labelling index (%) was 63.9+/-15.3 and 61.4+/-12.8 in sm cancer with and without lymph node metastasis, respectively. The lymph node metastasis was not significantly correlated to expression of p53 protein, bcl-2 protein or Ki-67 labelling index.
CONCLUSIONS
Expression of p53, bcl-2 protein and proliferative activity of sm cancer may not influence lymph node metastasis. Lymphatic invasion is a significant predictor of lymph node metastasis.

Methylotion Analysis of p16/INK4A in Gastric Low-Grade Mucosa-Associated Lymphoid Tissue Lymphomas after Helicobacter pylori Eradication Therapy.: Young A Kim, Sung Shin Park, Bo Young Lee, You Sun Kim, In Sung Song, Chul Woo Kim; Korean J Pathol. 2002;36(1):13-20.

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Abstract PDF: BACKGROUND
Inactivation of p16 has been associated with promoter region hypermethylation in different types of malignancies, including non-Hodgkin's lymphomas (NHLs). This loss of p16 was found frequently in cases of mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies indicate that promoter hypermethylation is often an early event in tumor progression in the follow-up of NHLs.
METHODS
To investigate the usefulness of p16 methylation in the diagnosis and follow-up of gastric low-grade MALT lymphomas, we analyzed methylation status of p16 using methylation-specific polymerase chain reaction methods in the sequential biopsy specimens of 13 patients with gastric low-grade MALT lymphomas undergoing Helicobacter pylori eradication therapy.
RESULTS
Five of thriteen cases showed p16 hypermethylation upon diagnosis. In four of five methylation positive cases, abnormal methylation was detected in the specimen even after the treatment, although there were no histologic evidence of disease. This methylation disappeared in the later samples of two of the cases, and they have remained in complete remission. Immunohistochemically, the loss of p16 protein expression was detected in one of three methylation-positive cases, and in none of the methylation-negative cases.
CONCLUSIONS
These results suggest that p16 methylation is relatively fequent in low-grade gastric MALT lymphomas, and it may have clinical applications in the management and follow-up of low-grade gastric MALT lymphomas.

Altered Expression of Nephrin, Glomerular Epithelial Cell Protein-1 (GLEPP1) and WT-1 in Glomerular Disease.: Byoung Kwon Kim, Ji Hoon Kim, Hyun Soon Lee; Korean J Pathol. 2002;36(1):21-29.

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Abstract PDF: BACKGROUND
Glomerular epithelial cell protein-1 (GLEPP1) and WT-1 expressed in mature visceral glomerular epithelial cell (VGEC) is required for maintenance of the mature status of VGEC. Nephrin protein is located at the filtration slit and regarded as a molecular component of the slit diaphragm. Alterations of these proteins in proteinuric diseases are not clearly defined.
METHODS
We investigated the expression of GLEPP1, WT-1 and nephrin in 28 renal biopsies diagnosed with minimal change nephropathy (n=10), focal glomerulosclerosis (n=10) and membranous nephritis (n=8) by immunohistochemical staining. Normal control biopsies were obtained from six nephrectomy specimens.
RESULTS
The patients consisted of 15 males and 13 females. The mean age was 40.7 years. Nephrotic range proteinuria (> or =3.5 g/day) was noted in 15 (54%) patients. GLEPP1 and nephrin expression were significantly decreased in patients as compared with those of the controls (p<0.05). The mean number of WT-1 expressing cells per glomerulus was also significantly decreased in patients as compared with those of the controls (p<0.05). However, there was no significant difference in the number of WT-1 expressing cells among the disease groups.
CONCLUSIONS
These results suggest that the loss of biological markers of mature VGEC may play an important role in the pathogenesis of proteinuria.

Placental Pathology in Intrauterine Growth Retardation.: So Young Park, Moon Young Kim, Yee Jeong Kim, Yi Kyeong Chun, Hye Sun Kim, Hee Soo Kim, Sung Ran Hong; Korean J Pathol. 2002;36(1):30-37.

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Abstract PDF: BACKGROUND
Histologic examination of the placentas from intrauterine growth retardation (IUGR) fetuses can supplement clinical knowledge of the cause of IUGR. The present study was undertaken to observe the pathologic findings regarding the placentas in IUGR fetuses.
METHODS
Clinicopathologic findings in 45 cases with IUGR at the third-trimester were reviewed, and they were compared with those of 24 normal control cases. An IUGR fetus was defined as one with a birth weight less than those in the 10th percentile. Of the IUGR cases, 15 were hypertensive IUGR with or without preeclampsia, and 30 were normotensive IUGR.
RESULTS
The IUGR groups had significantly shorter mean gestational ages, lower mean placental weights, and higher incidences of oligohydramnios, compared to the normal controls (p<0.05). Histologically, IUGR was characterized by increased incidence of decidual vasculopathy (31.1%, p<0.05), multiple and severe infarct (p<0.05), villous fibrosis (31.1%, p<0.05), syncytiotrophoblastic knots (86.7%, p<0.05), and higher degree of increased perivillous fibrin deposition (p<0.05). However, there were no statistically significant differences in the placental lesions between hypertensive and normotensive IUGR cases, except for the presence of decidual vasculopathy.
CONCLUSIONS
Abnormal uteroplacental vasculature and chronic uteroplacental insufficiency, coagulation-related pathology in the uteroplacental, intervillous and/or fetoplacental vasculature, and chronic inflammatory lesions may be the primary disease processes related to the placental pathology of IUGR. Although the cause of IUGR pregnancies is heterogeneous, careful cilinicopathologic correlations in individual cases are necessary in the interpretation of placental lesions of IUGR, and the total burden of several placental lesions may be more important than a single histologic feature.

The Pattern of Cell Proliferation and Apoptosis in Human Embryonic and Fetal Brain.: Suk Jin Choi, Jung Ran Kim; Korean J Pathol. 2002;36(1):38-44.

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Abstract PDF: BACKGROUND
Cell proliferation and apoptosis account for the major morphogenetic mechanisms during development of the central nervous system. We investigated these processes in developing human brains.
METHODS
We examined human embryonic and fetal brains. Cell proliferation was analysed by classical histology and MIB-1 immunohistochemistry; cell death was investigated by the TdT-mediated dUTP-biotin nick end labelling method.
RESULTS
Most proliferating cells were observed in the ventricular zone (VZ) in the 3rd-10th week of gestational age (GA), and in both the VZ and the subventricular zone (SV) in the 19-24th week of GA. The proliferation index of the VZ was highest in the 8th week of GA and then decreased as the GA advanced. Apoptotic cells were observed in the VZ as early as the 5th week of GA. They were also observed in the intermediate zone in the 19-24th week of GA, although they were significantly lower in amount compared to that in the VZ and SV.
CONCLUSIONS
These results suggest that apoptosis occurring early in the embryonic period is related to a cellular mechanism which selects and determines the cells that are committed to migration and differentiation during the development of the human brain.

Case Reports

Posttransplant Lymphoproliferative Disorder: A Report of 4 Cases.: Sunhee Chang, Jooryung Hugh, Kyung Mo Kim, Duck Jong Han, Seung Kyu Lee, Eunsil Yu; Korean J Pathol. 2002;36(1):45-50.

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Abstract PDF: Posttransplant lymphoproliferative disorder (PTLD) is a proliferation of B-cells associated with Epstein-Barr virus (EBV) infection as a complication of immunosuppression, especially by FK506. We investigated four cases of PTLD which developed either in allografts or in other organs.
Case
1 was a 38-year-old woman, who developed monomorphic PTLD in a kidney 7 years and 7 months after renal transplantation. Case 2 was a 37-year-old man, who developed monomorphic PTLD in the right submandibular lymph node 4 months after liver transplantation. Case 3 was a 60-year-old man, who developed monomorphic PTLD in the liver 8 months after liver transplantation. Case 4 was a 2-year-old female child, who developed polymorphic PTLD in the colon, liver, and mesenteric lymph node 10 months after liver transplantation. FK506 was administered to case 4. EBV was identified in the tissues of all cases by immunohistochemistry and/or in situ hybridization.

Pulmonary Lymphangioleiomyomatosis and Micronodular Pneumocyte Hyperplasia associated with Tuberous Sclerosis: A Case Report.: Gou Young Kim, Juhie Lee, Yong Koo Park, Youn Wha Kim, Jae Hoon Park, Moon Ho Yang; Korean J Pathol. 2002;36(1):51-54.

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Abstract PDF: Lymphangioleiomyomatosis (LAM) is characterized by a hamartomatous proliferation of smooth muscle cells in the lung, mediastium, and abdomen. In the lung, an abnormal proliferation of smooth muscle is seen along the airways, blood vessels, and lymphatics, resulting in honeycombing of the lung. It occurs in 0.1-1% of tuberous sclerosis (TSC) patients. Micronodular pneumocyte hyperplasia (MNPH) is a rare but distinctive pulmonary manifestation of TSC, and appears to be a hamartomatous proliferation of the type II pneumocytes. We report a case of pulmonary LAM and MNPH associated with TSC and bilateral renal angiomyolipoma in a 26-year-old woman. Immunohistochemically, the spindle cells of LAM were positive for HMB-45, but the type II pneumocytes of MNPH were negative.

Primary Choriocarcinoma of the Stomach: A Case Report.: Eun Joo Seo, Hi Jeong Kwon, Ki Ouk Min, Keun Woo Lim, Seong Lee, Byung Kee Kim; Korean J Pathol. 2002;36(1):55-58.

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Abstract PDF: A case of primary gastric choriocarcinoma with multiple liver metastases is described. A 54-year-old man underwent gastrectomy for an advanced cancer. An ulcerofungating tumor with extensive hemorrhagic necrosis was found in the anterior wall of the prepyloric antrum. The histologic examination revealed a biphasic pattern composed of uninucleated cyto or intermediate trophoblasts and syncytiotrophoblasts. A small area of the adenocarcinoma forming glandular structures and poorly differentiated solid sheets was also noted on the superficial portion of the tumor. Immunohistochemical staining for the beta human chorionic gonadotropin (-hCG) and the human placental lactogen (hPL) showed strong immunoreactivity, particularly in the cytoplasms of the syncytiotrophoblasts and intermediate trophoblasts, respectively. A diagnosis of the choriocarcinoma was made. Multiple hepatic nodules consistent with metastases were noted on the abdominal sonogram. The serum -hCG level of the patient was significantly increased.

Leiomyoma of the Ovary: A Case Report.: Hye Kun Oh, Yeun Kyung Lee, Sung Chul Lim; Korean J Pathol. 2002;36(1):59-61.

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Abstract PDF: We present a case of ovarian leiomyoma without related clinical symptoms in a 68-year-old woman. Leiomyoma arising primarily in the ovary is rare. However, it is believed that there are actually more cases than those reported because this condition is usually mistaken for a fibrothecoma or parasitic leiomyoma. Most cases previously reported were incidentally presented and coexisted with other ovarian lesions. The present case was characterized by a 9 cm, round lobulated mass that totally replaced the left ovary without uterine leiomyoma or coexisting ovarian lesions.

Mixed Germ Cell-Sex Cord-Stromal Tumor of Non-Gonadoblastoma Type of Ovary: A Case Report.: Kwangseon Min, Byungha Choi, Kyu Rae Kim; Korean J Pathol. 2002;36(1):62-65.

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Abstract PDF: We described a case of mixed germ cell-sex cord-stromal tumor of non-gonadoblastoma type (GCSCT-NG) of the ovary in a 2-year-old girl and compared its histological, immunohistochemical and ultrastructural findings with those of gonadoblastoma. The germ cell component showed an immunopositivity for cytokeratin and epithelial membrane antigen (EMA), and a negative reaction for -inhibin, alpha-fetoprotein (AFP), placental alkaline phosphatase (PLAP), vimentin and CD99. The sex cord elements showed an immunopositivity for cytokeratin, EMA, vimentin and inhibin, but negativity for AFP, PLAP, and CD99. The ultrastructural features showed desmosome-like cell junctions, suggesting spermatocytic differentiation from the primordial germ cells or gonocytes. Immunohistochemical and ultrastructural findings suggested that GCSCT-NG is probably a more differentiated form of mixed germ cell- sex cord-stromal tumor than gonadoblastoma.

Chordoid Glioma: A Case Report.: Jang Hee Kim, Jae Ho Han, Chull Shim; Korean J Pathol. 2002;36(1):66-69.

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Abstract PDF: The chordoid glioma is a recently recognized rare neoplasm of the third ventricle and hypothalamus and, as the name implies, has a chordoid appearance. Using histological, immunohistochemical and ultrastructural studies, we report a case of a 32-year-old man with a chordoid glioma in the third ventricle. Magnetic resonance T1-weighted images of the brain with homogenous contrast enhancement revealed a well circumscribed, isointense mass occupying the third ventricle. Histologically, the tumor showed cords and clusters of epithelioid cells within a mucinous background along with lymphoplasmacytic infiltrate, and appeared to be reminiscent of a chordoma or chordoid meningioma. Immunohistochemically, the tumor cells were immunoreactive for glial fibrillary acidic protein, vimentin and CD34 but negative for epithelial membrane antigen. Ultrastructural study revealed round to spindle shaped cells with abundant cytoplasmic intermediate filaments and cytoplasmic zonation.

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