Journal of Pathology and Translational Medicine

Volume 32(3); March 1998

Original Articles

Expression of Phospholipase C Isozymes in Radiation-Induced Tissue Damage and Subsequent Regeneration of Murine Small Intestine.: Sung Sook Kim, Yeong Ju Woo, Ju Ryung Huh, Jung Hyun Ryu, Kyung Ja Lee, Jung Sik Lee, Pann Ghill Suh; Korean J Pathol. 1998;32(3):155-161.

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Abstract PDF: Phospholipase C (PLC) isozymes play significant roles in transmembrane signal transduction. PLC- 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. The exact mechanisms of this signal transduction of tissue damage and subsequent regeneration, however, were not clearly documented. This study was planned to determine the biological significance of PLC isozymes following irradiation in rat small intestine. Sprague-Dawley rats were irradiated to the entire body by a single dose of 8 Gy. The rats were divided into 5 groups according to the sacrifice days after irradiation. The expression of PLCs in each group was examined by the immunohistochemistry and immunoblotting. The histologic findings were observed using hematoxylin and eosin staining. The regenerative activity, which was estimated by mitotic count and proliferatin cell nuclear antigen (PCNA) immunostaining, was highest in Group III (5th day after irradiation). By the immunohistochemistry, the expression of PLC- 1 was higher in Group III and Group II (3rd day after irradiation), and was found in the regenerative zone of the mucosa. The expression of PLC- 1 was highest in Group I (1st day after irradiation) and was dominantly in the damaged surface epithelium. The immunostaining of PLC- 1 was negative in all groups. The results of the immunoblotting study was compatible to that of the immunohistochemical study. Group II and III showed positive bands for PLC- 1, and group I and II for PLC- 1. These results suggest that PLC- 1 plays a significant role in mucosal regeneration following irradiation. PLC- 1 may play a role in radiation - induced mucosal damage.

Correlation between Helicobacter pylori Infection and Lymphoid Follicle Formation in Gastrectomy Specimens.: Won Ae Lee, Hye Sung Hahn, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1998;32(3):162-168.

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Abstract PDF: Histopathologic studies for Helicobacter pylori (H. pylori)-associated chronic gastritis have been mostly undertaken with endoscopic biopsy specimens, often leading to an inappropriate evaluation of the gastric mucosal alterations. The purpose of this paper was designed to investigate the actual prevalence of lymphoid follicle formation by H. pylori infection using the resected stomachs. A total of 16 fresh gastrectomy specimens bearing gastric carcinoma were examined under the quick and gentle procedure, with which H. pylori was detected in 12 cases (75%) and lymphoid follicles in 14 cases (87.5%), while the detection rate of H. pylori remained 56.3% in the control group which comprised the same 16 resected stomachs and were examined by routine tissue preparation procedure without any special care. There was a significant correlation between the presence of H. pylori and lymphoid follicle formation (p=0.05), but no correlation was found between the grades of H. pylori and lymphoid follicles. The topographical distribution of H. pylori or lymphoid follicles in antrum and body gave no statistical difference. Similarly, there was no correlation between H. pylori infection and intestinal metaplasia, activity of chronic gastritis or histologic types of accompanying adenocarcinoma. We conclude that studies of the gastric mucosal change by H. pylori infection using the gastrectomy specimens provide a useful information for analysis of lymphoid follicle formation which is a consistent morphological characteristic of H. pylori infection.

Expression of the pS2 Protein and Its Relation with Estrogen and Progesterone Receptor in Breast Cancer.: Eun Deok Chang, Chung Soo Chun; Korean J Pathol. 1998;32(3):169-173.

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Abstract PDF: Expression of the pS2 protein in breast carcinoma is a useful guide to evaluate the prognosis and response to tamoxifen. The pS2 protein is an estrogen-regulated 60 amino acid protein which was originally discovered following the screening of cDNA libraries in MCF-7 breast carcinoma cells and is induced through estrogen-dependent transcription of the pS2 gene. The presence of the pS2 protein in breast cancer is considered as valuable as the receptor status, or even more so, in predicting the response to hormonal therapy. We have investigated the pS2 protein expression in 62 cases of primary breast cancer in order to know the relationship between the expression rate of the pS2 protein and hormonal receptor status using immunohistochemical procedures on formalin-fixed and paraffin-embedded tissues. Concomitantly, both the estrogen receptors (ER) and progesterone receptors (PR) were examined using the immunohistochemical technique. Positive staining for the pS2 was seen in forty-nine cases (79%) of the tumors. Forty three cases (88%) of the pS2 positive tumors were ER positive and forty one cases (84%) of the pS2 positive tumors were PR positive ; forty six cases (93%) of pS2 positive tumors were positive for ER and/or PR. The pS2 status correlated significantly with the ER (p<0.0001) and PR (p<0.001). The results reveal a close association between the pS2 protein and either or both the ER and PR status.

The Relation between Cell Proliferation and Apoptosis According to the Histologic Types in Chemically Induced Rat Mammary Tumorigenesis.: Tae Jung Jang, Woo Hee Jung, Kwang Gil Lee; Korean J Pathol. 1998;32(3):174-185.

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Abstract PDF: Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoptosis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogenesis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7, 12-dimethylbenzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-beta. Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 mg/ml DMBA by oral intubation) and a control group. The results were as follows. 1. In the experimental group, breast tumors occurred in twenty two of fifty nine rats(37.3%, 22/59), and the total number of tumors was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompanied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced in intraductal proliferation, and lowest in ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the extent of its expression was less than 1% of all tumor cells; 5. TGF-beta was mainly expressed in the central portion of tumor cell nests rather than in peripheral portion, and TGF-beta immunoreactive tumor cells displayed good differentiation and did not reveal BrdU immunoreactivity. TGF-beta labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the suppression of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis. However, the suppression of apoptosis is not related to p53 mutation, bcl-2, and TGF-beta. TGF-beta seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.

Alteration in Extracellular Matrix Components in Preeclamptic Nephropathy.: Moon Hyang Park, Seung Sam Paik; Korean J Pathol. 1998;32(3):186-192.

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Abstract PDF: The preeclamptic nephropathy is characterized by swelling of endothelial cells, interposition of mesangial cells and matrix, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. To determine the distribution of extracellular matrix (ECM) components in preeclamptic nephropathy, the immunohistochemical study was performed in ten renal biopsy cases using antisera to human type I, III, IV, and VI collagens, fibronectin, and laminin. In preeclamptic nephropathy, the accumulation of type IV and VI collagens, fibronectin was observed in moderate amount in the mesangium and, to some extent, in the thickened capillary walls, particularly in the subendothelial layer. In segmentally sclerotic lesions seen in six cases, the amount of type IV collagen was partly decreased, whereas those of type VI collagen and fibronectin were slightly increased. Type I collagen was expressed to a mild degree in the expanded mesangium and segmentally sclerotic lesions. The results suggest that the expression of ECM in the mesangium is increased in preeclamptic nephropathy, and the deposition of ECM components may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions may be linked to the alternative accumulation of ECM components.

Expression of Proliferating Cell Nuclear Antigen and p53 Protein in Ovarian Epithelial Tumors.: Jong Jae Jung, Jong Hee Nahm, Chang Soo Park; Korean J Pathol. 1998;32(3):193-200.

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Abstract PDF: p53 gene mutation is commonly accepted to be associated with loss of negative cell cycle control and progression of tumors. The proliferative activity of tumor cells is considered to be a valuable indicator of tumor aggressiveness. This study is intended to compare p53 protein expression with cell proliferation rates in the ovarian epithelial tumors according to the various clinicopathological parameters. Immunohistochemistry using monoclonal p53 antibody (DO-1) and PCNA antibody (PC10) was applied to 56 cases of ovarian epithelial tumors including 17 cases of borderline tumor. The results were as follows. Both immunohistochemical staining of PCNA and p53 protein showed positive reactions confined to the nuclei of tumor cells. There were significant differences of p53 protein expression rates between borderline malignancies (11.8%) and cystadenocarcinomas (56.4%) of ovary. The expression rate of p53 protein was not significantly different according to the differentiation and the stage, but the cases of strong positive reaction to p53 protein were more frequently noted in the poorly differentiated and advanced staged tumors. The PCNA indices of p53 strong positive cases were higher than those of p53 weak positive cases. In summary, p53 protein and PCNA expression may be used as an adjuvant in differentiating borderline lesions from carcinomas of ovary and predicting their biological behaviors.

The Usefulness of Cytokeratin 7 and Colon Ovarian Tumor Antigen in the Differential Diagnosis of Primary and Metastatic Ovarian Tumors.: Eung Seok Lee, Hyun Deuk Cho, In Sun Kim; Korean J Pathol. 1998;32(3):201-207.

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Abstract PDF: Cytokeratin 7 has been known to be present in various types of human epithelial cells including the ovarian neoplasms, but not in colon cancers. The antibody to colon ovarian tumor antigen (COTA) has been introduced as a marker of colon and ovarian tumors. The aim of this study was to evaluate the usefulness of cytokeratin 7 and COTA in the differential diagnosis between ovarian primary and metastatic tumors. Nineteen primary ovarian epithelial tumors, seven metastatic carcinomas of the ovary from the stomach, three metastatic carcinomas of the ovary from the colon, one mucinous tumor of the ovary associated with a mucinous tumor of the appendix and pseudomyxoma peritonei, and nineteen colonic and twenty gastric adenocarcinomas were stained with monoclonal antibodies to cytokeratin 7 and COTA. The results are summerized as follows; In the primary ovarian tumors, 94.4% were positive for cytokeratin 7 and 50% were positive for COTA. In the primary colonic adenocarcinomas, 94.7% were negative for cytokeratin 7 and 68% were positive for COTA. In the metastatic ovarian tumor from the colonic adenocarcinomas, 100% were negative for cytokeratin 7 and positive for COTA. In the primary gastric adenocarcinomas, 40% were negative for cytokeratin 7 and 85% were negative for COTA. In the metastatic ovarian tumor from the gastric adenocarcinomas, 43% were negative for cytokeratin 7 and 14% were negative for COTA. From the results of this study, it could be concluded that in the differential diagnosis of primary ovarian tumors from metastatic colonic carcinomas, positive reaction for cytokeratin 7 suggests a primary ovarian tumor but a negative reaction for cytokeratin 7 and positive reaction for COTA suggest metastatic colonic carcinomas. The results of this study also reveal that cytokeratin 7 and COTA are not useful in the differential diagnosis of primary ovarian tumors from metastatic gastric carcinomas.

Histopathologic Findings & Expression of bcl-2 of the Endometrium Analysis of 1,000 consecutive biopsies of uterine bleeding .: Hye Kyung Lee, Dong Geun Lee, Ho Lee, Sang In Shim; Korean J Pathol. 1998;32(3):208-214.

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Abstract PDF: We evaluated 1,000 consecutive endometrial curettage samples obtained over a 30 month period. The clinico-pathologic correlation was analysed according to Hendrickson's five criteria based on the practical view. The causes of uterine bleeding in decreasing order of occurrence were as follows: 1) hormonal imbalance lesions (49.2%) encompassing glandular and stromal breakdown suggesting anovulatory bleeding, proliferative phase endometrium, and disordered proliferative endometrium, 2) pregnancy associated lesions (24.2%), 3) organic lesions (13.5%), 4) endometrial hyperplasia (6.9%), and 5) inadequate specimen (6.2%). According to age, pregnancy related lesions were most frequent in the third decade. In the fourth, fifth, and sixth decades, hormonal imbalance lesions were the most common cause. In approximately 30% of the samples, there were two or three morphologic patterns such as anovulatory bleeding with an endometrial polyp, postabortal bleeding with inflammation, and glandular-stromal dissociation with a polyp, which suggested there was a variable histologic morphology in the same disease spectrum. Using immunohistochemical techniques we studied the hormonal dependency of bcl-2 oncoprotein in anovulatory bleeding, endometrial hyperplasia, and proliferative endometrium. 70% of anovulatory bleeding specimens showed weak positivity in the epithelial cytoplasm, and all cases of endometrial hyperplasia and carcinoma showed a strong positivity. These results suggest that there is a estrogenic hormonal dependency of apoptosis in the endometrium.

Immunohistochemical Study of p53 and E-cadherin Proteins in Prostate Carcinoma.: Lee So Maeng, Won Il Kim, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1998;32(3):215-221.

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Abstract PDF: Considerable controversy exists concerning the value of histomorphological data in the assessment of the malignant potential of prostate carcinomas. Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. E-Cadherin is a specific epithelial cell-to- cell adhesion molecule which has previously been found to be expressed in well-differentiated non-invasive carcinoma cell lines, but it is lost in many poorly differentiated invasive cell lines. We performed immunohistochemical staining of p53 and E-cadherin in formalin fixed paraffin embedded tissues of 58 primary prostatic carcinomas. The expression rates of p53 and E-cadherin proteins in prostate carcinoma were positive in 15.5% and 44.8% of the cases, respectively. Histologically high-grade prostate carcinoma shows an increased expression of the p53 protein and a decreased one of the E-cadherin protein (P<0.05). The expression rates of the E-cadherin protein in prostate carcinoma decreased significantly according to the higher clinical stages and PSA levels (P<0.05). There was no accordance between the expression rate of p53 and E-cadherin. There were no significant correlation between each of the clinical stages and the expression rate of p53 protein or the PSA levels and the expression rates of p53 protein (P<0.05). Based on the present study, the expression of p53 and down regulation of E-cadherin are correlated with tumor progression and metastasis, and may be a useful prognostic factor in prostate carcinoma.

Case Reports

Intraductal Variant of Peripheral Cholangiocarcinoma of the Liver A report of three cases.: Won Mi Lee, Seok Hoon Jeon, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(3):222-225.

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Abstract PDF: Intraductal variant of peripheral cholangiocarcinoma is extremely rare. This variant shows intraductal growth and intraluminal extension without any infiltrative growth. The mode of intraductal growth is not known. The prognosis of this variant is better than that of usual cholangiocarcinoma. We report three cases, one of which is associated with Clonorchis sinensis (CS) infection. The tumors were entirely confined within the dilated peripheral tributaries of the intrahepatic bile duct. Microscopically, the tumors were well to moderately well differentiated, with a papillary or a micropapillary growth pattern. Focal clear cytoplasmic change and mucin production were noted. The tumors showed intraductal spreading without any invasion to the liver parenchyme. Mucosal hyperplasia and dysplasia were noted in the adjacent ducts. The authors assume that intraductal cholangiocarcinoma is a distinct subtype, and persistent irritation, such as, CS infection may undergo a malignant transformation through mucosal dysplasia.

Hyalinizing Trabecular Adenoma of the Thyroid: A case report.: Hyun ee Yim, Chull Shim, Euy Young Soh; Korean J Pathol. 1998;32(3):226-230.

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Abstract PDF: We report a case of hyalinizing trabecular adenoma of the thyroid gland with its immunohistochemical and ultrastructural features. A 53 year-old euthyroid woman presented a well defined small cold nodule on a thyroid iodine scan. Microscopically, oval and elongated tumor cells were arranged in trabeculae, clusters and a "zellballen" pattern resembling paraganglioma with scattered follicles. Nuclear features were characterized by fine nuclear grooves, acidophilic intranuclear cytoplasmic inclusions and perinucleolar halos. Abundant extracellular eosinophilic fibrohyaline matrix resembling amyloid were also noted. Immunostaining of tumor cells was positive for thyroglobulin and negative for calcitonin. In addition, tumor cells displayed an unexpected, unique cytoplasmic immunoreactivity for MIB1. Electron microscopy revealed euchromatic nuclei with grooves, intranuclear cytoplasmic inclusions, intermediate filament stuffed cytoplasms and abundant extracellular basal lamina material.

Primitive Neuroectodermal Tumor of the Kidney: A case report .: Sang Yong Song, Eun Youn Cho, Jung Won Lee, Jai Hyang Go, Mi Kyung Kim, Dae Shick Kim, Young Hyeh Ko; Korean J Pathol. 1998;32(3):231-236.

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Abstract PDF: Peripheral primitive neuroectodermal tumor (pPNET), a rare, highly aggressive neoplasm of indetermined histogenesis, occurs typically in the soft tissues of the chest wall and the paraspinal region. Comprehensive diagnostic studies including histological, ultrastructural, immunohistochemical and molecular analyses have been stressed to diagnose this entity. We report a case of primary renal PNET which was incidentally found in a 59-year-old man who presented with generalized weakness for 4 months. He was diagnosed as a non-insulin dependent diabetes mellitus 15 years ago and has been made well by oral therapy. An ill-defined mass, measuring 3.5 3 cm, located in the left kidney and perirenal fat, was incidentally found by ultrasonogram during a renal diabetic examination. The mass was resected because of the unresponsiveness against one-year chemotherapy and radiation therapy. Grossly, a homogeneously solid, gray-white mass, measuring 2.8 1.8 cm, was noted in the mid portion of renal cortex. The mass showed severe adhesion to the perirenal fatty tissue. Microscopically, tumor cells were rather uniform, small round with scanty cytoplasm and often showed rosette formation. Ultrastructurally, they showed membrane-bound dense core granules, measuring 125~150 nm, intercellular junctions and microvillous cytoplasmic projections. The tumor cells were uniformly immunoreactive for neuron-specific enolase and were focally immunoreactive for CD99 (013), chromogranin, synaptophysin and cytokeratin. They were not reactive for S-100 protein, vimentin, Leu-7, leukocyte common antigen, desmin and smooth muscle actin. To our knowledge, this is the smallest renal PNET in literature.

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