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Volume 39(4); August 2005
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Original Articles
Thrombospondin-1 and -2 Expressions in Hepatocellular Carcinomas: an Association with Tumor Angiogenesis and p53 Overexpression.
Jae Sin Chung, Ho Sung Park, Hyun Jin Son, Myoung Jae Kang, Woo Sung Moon
Korean J Pathol. 2005;39(4):215-221.
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AbstractAbstract PDF
Background
: It has been suggested that thrombospondin (TSP) is a p53-dependent negative regulator of tumor angiogenesis. TSP expression and localization in hepatocellular carcinomas (HCCs) and its association with overexpression of p53 protein were investigated. Methods : TSP-1 and -2 expressions were examined in 40 HCC specimens by immunohistochemical staining and in 4 HCC cell lines by Western blotting. In addition, p53 protein expression and microvessel density (MVD) were correlated with the TSP expression. Results : Strong immu- nopositivity for TSP-1 was observed in fibroblasts, vascular endothelial cells, and some vas- cular smooth muscle cells of the stroma in 18 cases (45%), and in tumor cells in 3 cases (7.5%) of 40 cases of HCC. Immunoreactivity for TSP-2 was observed in only the sinusoidal lining cells of the tumor in 15 cases (46%), and in tumor cells in 2 cases (6%) of 32 cases of HCC. TSP-1 expression was inversely correlated with MVD (p=0.028), but TSP-2 expression did not show any correlation with MVD. Although p53 was overexpressed in 17 cases, there was no significant correlation between TSP and p53 expressions. None of the HCC cell lines expressed TSP-1 or -2. Conclusions : These findings indicate that TSP-1 is mainly derived from nonparenchymal cells, and may decrease tumor angiogenesis in HCC.
An Analysis of p53, bcl-2 and Ki-67 Expressions, and Apoptosis in Rectal Cancer: Their Correlation with the Tumor Response after Preoperative Radiochemotherapy.
Jinyoung Yoo, Su Zy Kim, Hyeon Min Cho, Sung Whan Kim, Hyung Min Chin, Jung Yong Lee, Jun Ki Kim, Seok Jin Kang, Chung Soo Chun, Chang Suk Kang
Korean J Pathol. 2005;39(4):222-228.
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AbstractAbstract PDF
Background
: Preoperative radiochemotherapy (RCT) has been administered for locally advanced rectal cancer to increase the therapeutic benefits, and to preserve the sphincter in low-lying tumors, however, tumor responses after RCT are variable. Methods : Apoptotic index (AI), and expressions of Ki-67, p53 and bcl-2 were analyzed in pretreatment biopsies from 69 patients with rectal cancer by immunohistochemistry. Tumor response was graded in surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR). Results : CR was identified in 19 cases (28%), PR in 24 cases (35%), and NR in 26 cases (38%) of 69 cases. p53 protein was expressed in 49 cases (71%), whereas bcl-2 was in 42 cases (61%). The pretreatment Ki-67 labeling index was 65.4+/-3.4%. The tumor response was not associated with any of these markers. Tumors with CR/PR showed a higher AI (0.84+/-.84%/0.66+/-.52%) than that of tumors with NR (0.58+/-0.54%). There was a significant correlation between tumor response and the histologic differentiation (p=0.008) or recurrence (p=0.039). Conclusions : The AI revealed a tendency to increase in tumors with CR/PR, while expressions of p53 and bcl-2, and Ki-67 labeling index had little direct association with tumor response.
Expression Patterns of Tumor Related Proteins for Differential Diagnoses of Intrahepatic Adenocarcinomas.
Ghil Suk Yoon, Mi Sung Kim, Young Hwa Li, Ji Hyun Uhm, Sun Ju Kim, Tae Sook Kim, In Su Suh, Han Ik Bae
Korean J Pathol. 2005;39(4):229-235.
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AbstractAbstract PDF
Background
: Differential diagnoses of intrahepatic adenocarcinomas (IHAC) play an important role in the detecting primary sites and the determining type of treatment and overall prognosis of the patient. However, histopathologic findings alone have limitations of differential diagnoses of IHAC. Methods : To clarify which tumor related proteins (TRP) are useful for differential diagnoses of IHAC, TRP expression were investigated immunohistochemically, using MUC5AC, MUC2, mAb 91.9H, MUC1, and pS2, and by high iron diamine (HID) staining in 61 clinically confirmed IHACs. Results : MUC5AC (9/18, p<0.05) and MUC1 (17/18, p>0.05) displayed the most frequent expression in cholangiocarcinomas, and MUC2 (11/18, p<0.05), mAb 91.9H (16/18, p<0.05), and HID (16/18, p<0.05) in colorectal adenocarcinomas. pS2 (3/11, p>0.05) was expressed more often in pancreatic adenocarcinomas than other IHAC, while MUC2 and 91.9H were not expressed at all in pancreatic adenocarcinomas. The positivity of several TRP did not correlate with tumor differentiation. Conclusions : MUC5AC, MUC2, mAb 91.9H, and HID may be useful in differentiating cholangiocarcinomas from colorectal adenocarcinomas.
Loss of PTEN Expression in Breast Cancers.
Sun Hee Chang, Shi Nae Lee, Min Sun Cho, Heasoo Koo, Woon Sup Han, Seock Ah Im, Byung In Moon, Hyun Suk Suh, Hye Young Choi, Sun Hee Sung
Korean J Pathol. 2005;39(4):236-241.
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AbstractAbstract PDF
Background
: PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression.
Results
: Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.
Expression of Osteopontin, ZO-1 and E-cadherin in Adenoma and Adenocarcinoma of the Colon.
Yu Kyung Jeong, Mi Ja Lee, Sung Chul Lim, Keun Hong Kee, Ho Jong Jeon, Chae Hong Suh
Korean J Pathol. 2005;39(4):242-250.
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AbstractAbstract PDF
Background
: The expressions of osteopontin (OPN), zonula occludens-1 (ZO-1) and E-cadherin, known as cell adhesion-associated substances, were examined in adenoma and adenocarcinoma of the colon. The relationship of their expressions with clinicopathologic factors was examined to investigate the roles of these proteins in the development, invasion or metas- tasis of colon adenocarcinoma. Methods : The expressions of OPN, ZO-1, and E-cadherin were examined in 54 cases of adenoma and 67 cases of adenocarcinoma of the colon by immunohistochemical staining. Results : The expression of OPN in colon adenocarcinoma correlated with staging (p=0.012) and distant metastasis (p=0.021). The expression of ZO-1 was closely related with tumor cell differentiation (p<0.001), and the reduced expression of E-cadherin was associated with tumor cell differentiation (p=0.05) and lymph node metastasis (p<0.001). Co-expression of ZO-1 and E-cadherin was significantly associated with tumor cell differentiation, and the expressions of ZO-1 and E-cadherin were reduced or lost in all cases (5 cases) of poorly differentiated adenocarcinoma. Conclusions : Our data suggest that OPN is involved in the process of invasion and metastasis of colon adenocarcinoma, and ZO-1- and E-cadherin-mediated cell adhesion may play an important role in the differentiation of colon adenocarcinoma.
Expression of CD44 Isoforms and Its Significance in Renal Cell Carcinoma.
Ghil Suk Yoon, Hee Yeon Hong, Tae Sook Kim
Korean J Pathol. 2005;39(4):251-257.
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AbstractAbstract PDF
Background
: CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.
Expression of Actin-bundling Protein Fascin and its Relationship with Altered E-cadherin and beta-catenin Expressions in Ovarian Serous Neoplasms.
Eun Yoon Cho, YoonLa Choi, Seoung Wan Chae, Eo Jin Kim, Kyehyun Kim, Geung Hwan Ahn, Jin Hee Sohn
Korean J Pathol. 2005;39(4):258-264.
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AbstractAbstract PDF
Background
: Fascin, an actin-bundling protein, has been found in specialized normal cells, including the neuronal, endothelial and dendritic cells, and its expression is known to be greatly increased in various human neoplasms. Methods : Immunohistochemical stainings for fascin, betacatenin, and E-cadherin were performed in normal ovary tissue (n=13), and in benign (n=14), borderline (n=32), and malignant (n=74) ovarian serous neoplasms. We evaluated the fascin expression, and its relationship with the betacatenin and E-cadherin expressions, as well as the clinicopathologic factors. Results : Fascin expression was detected in the majority of the borderline (100%, 32/32) and malignant tumors (90.5%, 67/74), but it was not seen in the normal ovarian surface epithelial cells and the benign tumors (p<0.001). Fascin expression was significantly correlated with the occurrence of peritoneal metastases in the carcinomas (p=0.043). A significant relationship between the expressions of fascin and betacatenin (p=0.046), as well as E-cadherin (p=0.035) was noted. There was no significant correlation with the tumor grade of carcinoma, the FIGO stage, tumor recurrence, tumor-related death and the survival rate. Conclusions : In ovarian serous neoplasms, the fascin expression may be closely linked with tumor progression and metastasis, and it was associated with the up-regulation of betacatenin and E-cadherin.
Case Reports
Juxtaoral Organ of Chievitz: A Case Report.
Hyun Sil Kim, Jin Hak Kim, In Ho Cha, Tai Seung Kim, Mi Heon Ryu, Jin Kim
Korean J Pathol. 2005;39(4):265-268.
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AbstractAbstract PDF
The juxtaoral organ of Chievitz is an intramuscular embryonic structure of neuroepithelial origin, and is found near the insertion of the pterygomandibular raphae. The juxtaoral organ of Chievitz has no known function, however, its clinical implication and differential diagnosis should be considered. Here, we report a fibrous cord like mass in a 34-year-old woman that was incidentally found while her lower right third molar was extracted. Histologically, it showed epithelial cell nests with glandular or squamous differentiation, simulating odontogenic tumors or perineural invasion of carcinoma. However, they were positive for the S-100 protein, neuron specific enolase, the neural cell adhesion molecule, and nerve growth factor receptors by immunohistochemistry, supporting the theory that these cells are of neural origin. Awareness of the juxtaoral organ of Chievitz should be emphasized for the epithelial islands in this organ not to be misinterpreted as an invasive carcinoma, an odontogenic tumor, or perineural invasion by carcinoma.
Giant Cell Tumor with an Unusual Cartilage Matrix: A Case Report.
Ingu Do, Kyung Nam Ryu, Chung Soo Han, Yong Koo Park
Korean J Pathol. 2005;39(4):269-272.
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AbstractAbstract PDF
Giant cell tumor of bone is a locally aggressive benign neoplasm, which is composed of oval or plump, spindle-shaped mononuclear cells and uniformly distributed multinucleated giant cells. Bone or cartilage matrix production by the tumor cells is usually not seen. We present a pathologically proven case of giant cell tumor, arising in the acetabulum and pubic bone, with unusual cartilage matrix production. We also discuss the differential diagnosis from a chondroblastoma as well as a giant cell-rich osteosarcoma.
Synovial Sarcoma with Massive Myxoid Feature: A Case Report.
Joon Hyuk Choi, Young Ran Shim, Young Kyung Bae, Mi Jin Kim, Duk Seop Shin, Kil Ho Cho
Korean J Pathol. 2005;39(4):273-277.
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AbstractAbstract PDF
Focal myxoid change in synovial sarcoma is not uncommon, although the presence of predominantly myxoid stroma is very rare. Recognition of synovial sarcomas with massive myxoid feature is important because these can easily be mistaken for other myxoid soft tissue neoplasms. We report a case of a synovial sarcoma with massive myxoid feature in the left thigh of a 54-year-old woman. Wide excision of an 8.5*7.0*5.0 cm, well-circumscribed and lobulated tumor was performed. The cut surface was gray, soft, and myxoid. Histological examination showed proliferation of spindle cells in the predominantly myxoid stroma. There were small areas with features more typical of synovial sarcoma, including uniform, spindled cells with fascicular growth patterns, collagenous stroma, mast cell infiltration, and hemangiopericytoma-like vascular patterns. Immunohistochemical examination showed focal positivity of the tumor cells for epithelial membrane antigen (EMA). Tumor cells were all negative for cytokeratin (AE1/AE3), cytokeratin 7, S-100 protein, smooth muscle actin, and desmin. Ultrastructurally, tumor cells showed desmosomes and microvilli. Our case underscores that, in order to make a correct diagnosis, immunohistochemical and ultrastructural examination is essential.
Combined IgA Nephropathy and Membranous Glomerulonephritis : A Report of Six Cases.
Ji Han Jung, Yeong Jin Choi, Yong Soo Kim, Yoon Sik Chang, Byung Kee Bang, Sang In Shim, Chang Suk Kang
Korean J Pathol. 2005;39(4):278-283.
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AbstractAbstract PDF
IgA nephropathy (IgAN) and membranous glomerulonephritis (MGN) are common in adults. However, it is unlikely that these two distinct glomerulonephrites coexist in a renal biopsy. Here, we report clinical and pathological data of six patients with concomitant existence of IgAN and MGN in renal biopsy specimens from 1990 to 2004. Five patients were male and one was female, and their ages ranged from 29 to 71 years. Four patients had microscopic hematuria, five had nephrotic range proteinuria, three had hepatitis B virus infections, three had rheumatoid factors, one had antinuclear antibodies. Two cases were developed after kidney transplant. Immunofluorescence microscopy showed characteristic findings of mesangial IgA deposits and granular IgG deposits on the capillary walls. These were confirmed by electron microscopic findings of immune-type electron-dense deposits in the mesangium and subepithelial capillary basement membranes. The pathogenesis and prognosis of the patients are discussed in this report.
Angiomyolipoma of the Nasal Cavity.
Jai Hyang Go
Korean J Pathol. 2005;39(4):284-286.
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AbstractAbstract PDF
Nasal angiomyolipomas are exceedingly rare and usually present as small tumors in middle-aged or old men. Their histology is similar to that of the renal counterpart, but they differ in the absence of epithelioid cells, the lack of HMB-45 immunoexpression and no association with tuberous sclerosis. A case of angiomyolipoma occurring in the right nasal cavity was presented in a 44-year-old male patient. The mass was removed by an endoscopic approach. A well-circumscribed, 1.3 cm-sized, ovoid mass was composed of yellowish gray, solid, soft tissue. Histologically, it consisted of bundles of smooth muscles, mature fat cells and thick-walled blood vessels. Nests of seromucous glands were admixed within the mass. Neither epithelioid nor pleomorphic cells were found, and HMB-45-positive cells were not detected. No recurrence has been detected for 2 months after the operation.
A Case of Metastatic Hepatocellular Carcinoma of the Ovary: An Immunohistochemical Study and Literature Review.
Mi Jin Kim
Korean J Pathol. 2005;39(4):287-290.
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Hepatocellular carcinomas rarely metastasize to the ovaries. To our knowledge, only nine cases of metastatic hepatocellular carcinoma of the ovary have been reported in the literature. Here, we present an additional case in which an ovarian lesion was the initial presentation in a 43-year-old female patient. An exploratory laparotomy revealed a left ovarian solid mass measuring 6.5*4.0*3.5 cm, with a lobulated greenish brown sectioned surface. A subsequent ultrasonogram and CT scan revealed a concurrent hepatic mass, and laboratory tests showed high serum AFP and CA125 levels. Microscopically the tumor showed predominantly solid and trabecular patterns, and intercellular canaliculi containing bile pigments. A postoperative hepatic biopsy confirmed the hepatocellular carcinoma. The main differential diagnosis involved ovarian metastasis of the hepatocellular carcinoma, the hepatoid carcinoma of the ovary with liver metastasis, and a hepatoid yolk sac tumor. Diagnosis in such cases should be reached by careful clinical evaluation and a thorough pathologic examination accompanied by a histochemical and immunohistochemical work-up.

J Pathol Transl Med : Journal of Pathology and Translational Medicine