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Volume 31(3); March 1997
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Original Articles
Loss of Heterozygosity Affecting the APC and p53 Tumor Suppressor Gene Loci in Colorectal Cancers and Its Prognostic Significance.
Eun Deok Chang, Won Sang Park, Byung Kee Kim, Sun Moo Kim, Sang In Shim
Korean J Pathol. 1997;31(3):191-200.
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AbstractAbstract PDF
Development of the human colorectal cancer is associated with several distinct genetic abnormalities involving both dominant-acting oncogenes (K-ras, c-src) and tumor suppressor genes (APC, DCC, p53) which undergo inactivation or loss. In colorectal tumors, the common molecular alteration is localized in the 17p13 and 5q21 loci encoding the p53 and the APC gene, respectively. The identification of these genes may help the understanding of the pathogenesis of colorectal neoplasia. In order to determine whether the frequency of the genetic alterations varies with sex, age, tumor size, or site, including pathologic parameters, such as degree of differentiation, tumor stage, mucin component, lymphoid reaction, tumor invasion pattern, vein and nerve invasion, lymph node metastasis, and other parameters, such as disease-free survival, distant metastasis and patient outcome, the authors analyzed the loss of heterozygosity (LOH) of the APC and the p53 genes in paraffin-embedded specimens of 48 colorectal cancers by use of the polymerase chain reaction and restriction fragment length polymorphism. The results were as follows: the LOH affecting the APC was found in 15 out of 31 (48.4%) heterozygous patients, while the LOH of the p53 locus was observed in 11 out of 26 (42.3%) patients. Among 48 patients, the LOH at both the APC and the p53 loci was observed in five (10.4%) patient. No statistically significant associations were found between the LOH of the APC gene and the proposed parameters. The relationship between the LOH of the p53 and the histologic differentiation, lymphoid reaction was significant (P<0.05), but survival was not correlated. Statistically significant associations were found between overall survival of the colorectal cancer patients and distant metastasis, Astler-Coller stage, lymphoid reaction, invasion pattern, nerve invasion, vein invasion, lymph node metastasis, and disease free survival. The above results suggest that the LOH of the p53 genes could be involved in the progression of colorectal cancers. However, neither the LOH of the APC nor that of the p53 have significant association with survival of the colorectal cancer patients.
Heat Shock Protein 70 and p53 Protein Expression in Colorectal Adenomas and Carcinomas.
Tae Jung Jang, Jung Ran Kim, Kung Bae Lee
Korean J Pathol. 1997;31(3):201-210.
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AbstractAbstract PDF
Heat shock protein 70 (HSP70) is a chaperone that binds to mutant p53 and consequently can regulate its accumulation or localization. Its expression is upregulated in tumor cells. We studied 44 adenomas and 29 carcinomas of colorectum to evaluate the expression of HSP70, and to assess the correlation among p53 protein and other clinical prognostic parameters. HSP70 expression was scored according to staining intensity and extent. p53 protein expression was 45.5%(20/44) in adenomas and 79.3%(23/29) in carcinomas(P<0.01). p53 protein expression of carcinomas was 57.1%(4/7) in diploidy tumors, 100.0%(8/8) in aneuploidy tumors(P=0.07), 100.0%(8/8) in well-differentiated tumors, and 50.0%(2/4) in poorly differentiated tumors(P= 0.09). HSP70 expression mainly revealed a fine granular cytoplasmic staining pattern in tumor cells. HSP70 was focally detected in some lymphocyte, ganglion cell and normal mucosa. HSP70 expression was 46.3%(19/41) in adenomas and 93.1%(27/29) in carcinomas. HSP70 score was 0.9+/-1.3 in adenomas(n=41) and 5.5+/-3.5 in carcinomas(n=29)(P<0.0005). Its score was 1.7+/-1.6 in p53 positive adenomas and 0.3+/-0.6 in p53 negative adenomas(P<0.005), and its expression rate was higher in p53 positive carcinomas than p53 negative carcinomas (P>0.05). There was no significant correlation among HSP70, tumor size, Dukes'stage, nodal metastasis, depth of tumor invasion, DNA ploidy and tumor differentiation. In conclusion, HSP70 and p53 protein appear to be correlated to each other, and that HSP70 and p53 protein may play a certain role in the progression of colorectal tumor. Further studies are needed for determining their prognostic factors in colorectal carcinoma.
The Correlation between the Proliferative Activity in Biopsied Specimen of Gastric Adenocarcinoma and the Pathologic Findings of Resected Specimen.
Hye Sun Kim, Jae Bok Lee, Se Min Kim, Jong Sang Choi, Han Kyeom Kim
Korean J Pathol. 1997;31(3):211-218.
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AbstractAbstract PDF
Studies on the correlation between proliferative activity of biopsied specimen and pathologic findings of resected specimen have been carried out to find the prognostic factors. To estimate the proliferative activity, 100 cases of biopsied specimen of gastric adenocarcinoma were tested for the PCNA (proliferating cell nuclear antigen) and the AgNOR (argyrophilic nucleolar organizer region) by the immunohistochemical and histochemical stainings, respectively. The resected tumors classified by histologic type, differentiation, depth of invasion, and nodal metastatic status were followed by cell cycle analysis using flow cytometry. The PCNA LI (labelling index) were higher in well or moderately differentiated tumors (P<0.01) than the poorly differentiated ones and the aneuploid tumors (P<0.05) more than in diploid ones. However, there were no correlations among histologic types, depth of invasion, nodal metastatic status and PCNA LI. The AgNOR counts were higher in advanced tumor than in the EGC (early gastric cancer) (P<0.01). In cases with nodal metastasis, most of them showed the AgNOR counts higher than those without nodal metastasis. There were no correlations between the AgNOR counts and the DNA ploidy, histologic type, or differentiation. High PCNA LI and high AgNOR counts were shown in cases with advanced tumors (P=0.000) and nodal metastasis (P<0.05). No correlation was shown with the histologic type or differentiation. The results show that proliferative activity of the biopsied specimen of gastric adenocarcinoma is correlated with the differentiation and the invasion depth of resected specimen. Especially, better correlation is obtained by analyzing both the PCNA LI and the AgNOR counts than by analyzing each.
Sequential Studies of Glomerular Crescent Formation in Rabbits with Anti-Glomerular Basement Membrane(GBM) Antibody Induced Glomerulonephritis(GN).
Hye Seon Ahn, Jung Woo Noh, Moon Hyang Park
Korean J Pathol. 1997;31(3):219-232.
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AbstractAbstract PDF
To investigate the mechanism of crescent formation, sequential pathologic changes from the New Zealand White rabbits with anti-GBM antibody induced GN by administration of guinea pig anti-GBM IgG were studied by light (LM), immunofluorescent (IF) and electron (EM) microscopy. Although no glomerular changes were observed in LM, swelling of the endothelial cells and the epithelial cells were noted in EM by day 2. By day 7, early and cellular crescents were evident. Proteinaceous materials and fibrins were noted in the glomerular capillary lumina (GCL) and Bowman's space (BS) associated with segmental hypercellularity. The GBM damage became progressively severe, followed by focal detachment of the visceral epithelial cells from the GBM. At day 14, fibrin strands, mononuclear cells and collagen fibrils were present between the proliferating extracapillary cells. At day 31, fibrocellular crescents were predominated. Elongated spindle cells, morphologically resembling myofibroblasts, were noted near the Bowman's capsule (BC). A degree of tubular atrophy, interstitial fibrosis, and inflammatory infiltrates increased as it did with fibrous organization of crescent. Intense linear IF staining for IgG and C3 were seen throughout the experiments along the GBM. In conclusion, the progression of crescent from an early "proteinaceous" stage through cellular, fibrocellular and fibrous stages was well documented in this study. Inflammatory cells and coagulation mechanism may activate the initiation of the GBM damage at the early stage. Activated periglomerular mononuclear cells may also cause disruption of BC which facilitates entry of activated periglomerular cells and fibroblasts into BS leading to progressive fibrous crescent formation.
Congenital Cystic Disease of the Kidney overview and a classification.
Mee Joo, Yeon Mee Kim, Chong Jai Kim, Yeon Lim Suh, Jeong Wook Seo, Je Geun Chi
Korean J Pathol. 1997;31(3):233-243.
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AbstractAbstract PDF
The congenital renal cystic disease encompasses a complex group of pathologic and clinical entities. We retrospectively reviewed 42 cases of congenital renal cystic lesions classified into four Potter types in a series of 2,063 consecutive autopsies from 1981 to 1996. According to our study based on morphologic, clinical, genetic features and associated anomalies, type I and III are relatively compatible with Potter's original definition. However, it was reasonable that type II and IV are classified to the same group because of: 1) very similar histologic findings representing dysplastic kidney, 2) many associated anomalies, 3) no evidence of inheritance, and 4) presence of a combined type. Syndrome associated cysts, such as Meckel-Gruber syndrome, were also separately classified. If the dysplastic evidence was insufficient for diagnosis to the dysplastic kidney in type II and IV, then these cases would be better classified into a cystic disease associated with congenital hydronephrosis. We propose a classification of the congenital cystic disease of the kidney to be: 1) dysplastic kidney, 2) cystic disease associated with congenital hydronephrosis, 3) polycystic kidney, and 4) syndromic cystic disease.
The Effect of Bacterial Lipopolysaccharide on the Lymphokine Production of the T Lymphocytes.
Hyung Bae Moon, Ki Jung Yun, Won Chul Han, Chae Woong Lim, Hyuk Nyun Kwon, Young Soon Park
Korean J Pathol. 1997;31(3):244-251.
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AbstractAbstract PDF
It is well known that the murine T helper cell clones are divided by their lymphokine secretory activities. One is the Th-1 cell, producing IL-2 and IFN after stimulation and the other is the Th-2 cell, producing the IL-4 and IL-5. This study was undertaken to evaluate the immunomodulatory properties of the bacterial lipopolysaccharide(LPS) on the lymphokine production in vivo and in vitro. The results were as follows: There were no effects on the lymphokine secretion by the in vitro treatment of the LPS. The in vivo treatment of the LPS decreases the capability of the production of IL-2 and IFN , whereas it increases the capability of IL-4 production. The altered capacity of the lymphokine production was recovered about 2 weeks after the treatment of the LPS. There were no differences on the lymphokine production between E-coli LPS and salmonella LPS. The capacity of the lymphokine production was the same in the treatment of a non-heated LPS or heated-LPS. The lymphokine production of the mice which were desensitized by the long term treatment of the LPS was not different from the control mice. The in vitro treatment of RU486 can block the alterations of the lymphokine production after the treatment of the LPS. In summary, one can tell that the LPS increases the secretion of the IL-4 through the endogenous secretion of the glucocorticoids.
Case Report
Carcinosarcoma and Multiple Early Gastric Carcinomas of the Stomach.
Won Mee Lee, Young Ha Oh, Moon Hyang Park, Kwang Su Lee, Jung Dal Lee
Korean J Pathol. 1997;31(3):252-256.
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AbstractAbstract PDF
We report a rare case of carcinosarcoma arising in the stomach. The tumor is presented in the posterior wall of the gastric lower body and antrum of a 56-year-old man. Grossly the tumor has polypoid appearance with diffuse surface ulceration and measures 5.5 cm in diameter. The tumor is accompanied with three separate well differentiated early gastric adenocarcinomas (two EGC type IIc & IIa). Microscopically, the tumor consists of moderately well differentiated adenocarcinoma in the periphery, and lobulated sarcomatous areas in the center, which shows chondroid differentiation. Transitional areas between adenocarcinoma and chondrosarcoma are evident. Immunohistochemical studies show positivity for cytokeratin and carcinoembryonic antigen in the epithelial component, and for vimentin and S-100 in the sarcomatous component. The transitional areas are positive in carcinoembryonic antigen, vimentin, S-100, and cytokeratin. The tumor extended to the subserosa and showed metastasis of only adenocarcinomatous component in six out of 47 dissected perigastric lymph nodes.
Original Article
Large Cell Neuroendocrine Carcinoma of the Lung 2 cases including one presented as an ovarian mass.
Yun Jung Kim, Jung Weon Shim, Hye Kyung Ahn, Young Euy Park
Korean J Pathol. 1997;31(3):257-262.
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AbstractAbstract PDF
Pulmonary tumors exhibiting neuroendocrine differentiation are classified as typical carcinoid, atypical carcinoid, and small cell lung carcinoma(SCLC). Travis et al. proposed a fourth category of large cell neuroendocrine carcinoma, which is characterized by light microscopic neuroendocrine appearance, cells of large size, polygonal shape, low nuclear cytoplasmic ratio, coarse nuclear chromatin, with prominent nucleoli high mitotic rate and frequent necrosis; and neuroendocrine features by immunohistochemistry or electron microscopy. High grade neuroendocrine carcinoma (LCAC-NE) revealed aggressive clinical course. We report two cases of neuroendocrine tumors of the lung characterized by a trabecular pattern of large pleomorphic cells with frequent mitoses and wide necrosis. The frequent metastatic sites of atypical carcinoid were liver, bone and brain. One of our case is presented, at first, as an ovarian mass, which shows multifocal rosettes and revealed metastasis from lung. Both cases expressed neuroendocrine differentiation by light microscopy and immunohistochemistry. However clinical neuroendocrine symptom were not present.
Case Report
Acute Renal Failure Associated with Gross Hematuria in a Patient with Focal Glomerulonephritis.
Hee Jung Kim, Hyeon Joo Jeong, Dae Suk Han
Korean J Pathol. 1997;31(3):263-268.
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AbstractAbstract PDF
A 58-year-old female with an episode of gross hematuria two months before and fever and chill for the past three days presented oliguric acute renal failure. She has taken NSAID intermittently for 18 years due to rheumatoid arthritis, and herb medicine for one week two months ago when gross hematuria developed. Physical examination revealed mild tenderness on costovertebral angles. Her blood pressure was 170/100 mmHg, the urinalysis showed >300 mg protein with many RBCs and 10-20 WBCs and the serum creatinine was 5.8 mg/dl. A renal biopsy performed on the 4th hospital day showed that it was overwhelmed by severe tubular lesions which reveal intratubular obstruction by massive erythrocyte casts and tubular necrosis. The glomeruli showed focal minimal crescents with many red blood cells entrapped in the crescents and in the capillaries. Immune deposits were not present. A renal failure resolved spontaneously and the patient was discharged three weeks later with creatinine of 2.4 mg/dl. In this patient, acute renal failure was considered to be due to a tubular lesion related to the glomerular bleeding from focal glomerulonephritis revealing minimal crescents.
Original Article
Intra-abdominal Angiosarcomatosis Induced by Irradiation.
Hee Jin Chang, Youn Joo Kim, Sung Eun Yang, Sung Sook Paeng, Jung Il Suh
Korean J Pathol. 1997;31(3):269-274.
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AbstractAbstract PDF
Therapeutic irradiation can induce angiosarcoma. Radiation-induced angiosarcoma constitutes 20% of all angiosarcomas. Although its common site of origin is the skin and subcutaneous tissue, it rarely arises in small or large bowels with a presentation as multifocal abdominal angiosarcomatosis. We report a case of intra-abdominal angiosarcomatosis involving the jejunum, ileum, transverse colon, mesentery and right ovary in a 63-year-old female. It developed 10 years after therapeutic irradiation for squamous cell carcinoma of uterine cervix. She developed panperitonitis due to intestinal perforation. She died from sepsis 3 days after segmental resection of the small bowel and right oophorectomy. We reviewed the previously reported cases and describe the clinicopathologic features of this tumor.
Case Reports
Congenital Hepatic Fibrosis with Caroli's Disease.
Yoon Jung Kim, Soon Ae Oak, In Chul Lee
Korean J Pathol. 1997;31(3):275-279.
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AbstractAbstract PDF
Congenital hepatic fibrosis is an inherited, congenital disorder of the liver, and is occasionally associated with cystic disease of the liver and kidney. We present a case of congenital hepatic fibrosis with Caroli's disease. A 21-year-old woman had suffered from an episodic fever with headaches for 3 years. In laboratory examination, the liver function test was within the normal limits. Esophageal varix was noted by an endoscopic examination. Hepatosplenomegaly and multiple dilated bile ducts were seen by abdominal CT scanning. An orthotopic whole liver transplantation was done. The liver was fibrotic and enlarged. Multiple cystically dilated intrahepatic ducts were noted. Microscopically, diffuse portal fibrosis and widening with proliferation of bile ductules were seen. Intrahepatic bile ducts were markedly dilated and tortuous. The liver cell cords were well preserved.
Malignant Glomus Tumor Arising in Benign Glomus Tumor.
Seung Sam Paik, Eun Sun Kim, Young Chun Moon, Chan Kum Park, Moon Hyang Park, Jung Dal Lee
Korean J Pathol. 1997;31(3):280-283.
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AbstractAbstract PDF
The glomus tumor is a distinct neoplasm composed of modified perivascular smooth-muscle cells identical to those described in the glomus body. Malignant glomus tumor, also referred to as glomangiosarcoma, is exceedingly rare. It has been subdivided into locally infiltrative glomus tumor, glomangiosarcoma arising in a benign glomus tumor, and glomangiosarcoma arising in de novo. A few cases of malignant glomus tumor arising in a benign glomus tumor have been reported. A 55-year-old man underwent resection of a solitary nodule in the right shoulder area. The tumor was biphasic with a typical benign glomus tumor at the periphery and the central sarcomatous area composed of oval to elongated pleomorphic cells with a single prominent nucleolus and occasional mitotic figures. Both tumor components showed intense staining for vimentin, smooth muscle actin, and muscle specific actin. Herein, we report a case of a malignant glomus tumor arising in a benign glomus tumor with an immunohistochemical study and a review of literatures.
A Cystic Mesothelioma in the Inguinal Area.
Im Joong Yoon, Nam Bok Cho, Tae Jin Lee, Mee Kyung Kim, Se Chul Kim, Kye Yong Song
Korean J Pathol. 1997;31(3):284-287.
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AbstractAbstract PDF
The cystic mesothelioma is a very rare tumor which has a clinically and histologically benign nature. Here in reported is the case of a cystic mesothelioma presented as a palpable mass of the inguinal area in a 28-year-old male. Ultrasound showed a cystic tumor at the inguinal canal, and the other physical and laboratory examinations were within normal limits. Grossly, the tumor consisted of cysts containing clear serous fluid and focally solid areas. Microscopically, the tumor was encapsulated with fibrocollagenous wall, and the tumor cells were cuboidal or polygonal epithelial cells with single or multiple layers and had clear cytoplasm. Some areas showed thyroid follicle-like structures. The content of follicle-like structures showed eosinophilia in the H&E section, but positive in mucin stain. Neither cytologic atypia nor mitoses were present. Immunohistochemical staining revealed positive reaction for keratins of low molecular weight, while negative for the thyroglobulin and CEA. These findings suggested mesothelial in origin. We concluded that this tumor was primary rather than metastatic, because he had no evidence of a tumor in gastrointestinal, genitourinary tracts and scrotum.

JPTM : Journal of Pathology and Translational Medicine