Journal of Pathology and Translational Medicine

Volume 40(5); October 2006

Original Articles

Assessment of Apoptosis by M30 Immunoreactivity and the Relationship with the MSI status and the Clinicopathological Characteristics of Colorectal Carcinomas.: Hyun Jeong Kang, Mee Young Sol, Do Youn Park, Soo Han Lee, Dong Hun Shin, Jee Yeon Kim, Kyung Un Choi, Hwal Woong Kim, Chang Hun Lee, Gi Young Huh; Korean J Pathol. 2006;40(5):319-325.

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Abstract PDF: BACKGROUND
The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 that's produced during the process of apoptosis, and it is reactive in formalin-fixed, paraffin-embedded tissue. The detailed nature of apoptosis in colorectal cancer is unclear, especially in regard to the MSI status and the clinicopathologic factors. The purpose of this study was to elucidate the apoptosis assessed by M30 immunoreactivity in colorectal cancer and its relationship with the MSI status and the various clinicopathologic factors of colorectal cancers.
METHODS
101 colorectal cancers were classified according to levels of MSI as 12 MSI-H, 4 MSI-L and 85 MSS. Apoptosis was quantified by immunohistochemistry with using M30 CytoDEATH anti-body.
RESULTS
The apoptotic index assessed by M30 was significantly increased in the MSI-H and MSI-L colorectal cancer compared to that in the MSS colorectal cancer. Right sided colon cancer showed a significant higher apoptotic index than did the left sided colon cancer. There was also a tendency for decreased apoptosis in metastatic colorectal cancers (Duke's stage D). There was somewhat of an increase of apoptosis in colorectal cancers with mucinous carcinoma and medullary carcinoma, and also in the colorectal cancers with an increased TIL count, but this was not statistically significant.
CONCLUSION
M30 immunoreactivity is a valuable method to detect apoptosis in formalin-fixed, paraffin-embedded tissue and it might explain that MSI-H colorectal cancer shows better clinical behavior than MSS colorectal cancer in regard to the increased apoptosis.

Significance of Galectin-3 Expression in Pulmonary Non-Small Cell Carcinoma.: Dong Hoon Shin, Chang Hun Lee, Hyun Jung Kang, Mee Young Sol, Min Ki Lee; Korean J Pathol. 2006;40(5):326-332.

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Abstract PDF: BACKGROUND
Non-small cell carcinoma (NSCC) has become the leading cause of cancer related death around the world. However, its prognostic factors remain poorly defined. Galectin-3 is an apoptosis related protein and its relationship with various cancers is presently the subject of research. This study was performed to investigate galectin-3 expression in NSCC and its value as a prognostic factor. METHODS: We examined the expression of galectin-3 and bcl-2 in surgically resected, lung NSCC, including 61 squamous cell carcinomas and 41 adenocarcinomas. PCNA staining was also performed. RESULTS: Each type of carcinoma showed cytoplasmic positivity in 18 (30.0%) and 25 (61.0%) cases, respectively. Squamous cell carcinoma showed increased galectin-3 expression in better differentiated tumors, whereas adenocarcinoma didn't show any relationship with the degree of differentiation. The cytoplasmic positivity of galectin-3 in both types of carcinoma was associated with poor prognosis. Bcl-2 expression didn't show any significant relationship with overall survival. Galectin-3 and bcl-2 expressions were positively correlated. However, co-expression of both proteins was not related to prognosis. CONCLUSIONS: These results indicate that galectin-3 expression in NSCC warrants attention as a possible prognostic factor.

Expression of Survivin, HSP90, Bcl-2 and Bax Proteins in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Sang Dae Lee, Sung Woong Park, Soon Auck Hong, Gui Young Kwon, Tae Jin Lee; Korean J Pathol. 2006;40(5):333-338.

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Abstract PDF: BACKGROUND
Survivin belongs to the inhibitor of apoptosis family, and it has recently been found to be expressed in most solid tumors. Therefore, its expression is suggested to have prognostic significance. However, no data are available concerning the significance of survivin for the carcinogenesis of bladder cancer.
METHODS
In order to induce urothelial tumor in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was administered to male Sprague-Dawley rats for 30 weeks. We used immunohistochemistry to investigate the expressions of survivin, HSP90, Bcl-2 and Bax in rat bladder carcinogenesis.
RESULTS
Urothelial cell hyperplasia, papilloma, non-invasive urothelial carcinoma and invasive urothelial carcinoma appeared at 5, 10, 20 and 30 weeks, respectively. The expressions of survivin and HSP90 increased sequentially from normal mucosa, hyperplasia, papilloma, non-invasive urothelial carcinoma to invasive urothelial carcinoma. The expressions of Bcl-2 and Bax did not increase, however the number of cases with more than 1 of Bcl-2/Bax expression ratio increased sequentially during the progression of urothelial lesion. The expression of survivin showed a statistically significant correlation with the expression of HSP90 and the Bcl-2/Bax expression ratio.
CONCLUSIONS
Our findings suggest that survivin may be involved in the carcinogenesis of rat bladder and its expression is correlated with the expression of HSP90 and the Bcl-2/Bax expression ratio.

Genistein Induces G2/M Cell Cycle Arrest and Apoptosis in Rat Neuroblastoma B35 Cells; Involvement of p21(waf1/cip1), Bax and Bcl-2.: Ismail A Ismail, Ku Seong Kang, Jung Wan Kim, Yoon Kyung Sohn; Korean J Pathol. 2006;40(5):339-347.

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Abstract PDF: BACKGROUND
The effect of genistein on different types of cells has been investigated. However, its effect on the nervous system is still unclear. The aim of the present work is to explore the effect of genistein on rat neuroblastoma B35 cells.
METHODS
The effect of genistein on the proliferation of B35 cells, its cytotoxicity, the cell-cycle distribution, the ultra-structural changes and the induction of apoptosis were determined using MTT assay, LDH assay, Flow-cytometric analysis, transmission electron microscopy and Hoechst staining, respectively. Furthermore, Real-time quantitative RT-PCR and Western blotting were used to examine the transcriptional and post-translational alterations of the G2/M cell-cycle arrest marker cyclin-dependent kinase inhibitor p21(waf1/cip1) and the apoptosis-related genes after genistein treatment.
RESULTS
Genistein significantly inhibits cell survival, slightly elevates the release of lactate dehydrogenase and induced apoptosis in B35 cells. Genistein increased the number of cells at S-phase and induced cells to accumulate at the G2/M phase. These G2/M arrested cells are associated with a marked up-regulation of p21(waf1/cip1) at both the mRNA and protein levels. We observed that genistein up-regulates pro-apoptotic Bax with concurrent down-regulation of the anti-apoptotic Bcl-2 protein.
CONCLUSION
These observations suggest that the anticancer effect of genistein on B35 neuroblastoma cells is mediated through multiple cellular pathways including G2/M cell-cycle arrest and the induction of apoptosis.

Clinicopathological Analysis of Eight Cases of Idiopathic Portal Hypertension.: Kyungeun Kim, Young Suk Lim, Kyung Mo Kim, Eunsil Yu; Korean J Pathol. 2006;40(5):348-353.

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Abstract PDF: BACKGROUND
Idiopathic portal hypertension (IPH) is a rare clinicopathologic entity that shows clinical evidences of portal hypertension with no pathologic features of cirrhosis.
METHODS
The clinical and pathologic features of 8 cases with IPH were analyzed via the medical records along with the biopsy or resected liver specimens.
RESULTS
Six patients were male and two were female. The chief complaints were sudden variceal bleeding in seven patients and abdominal pain in one patient. Six patients were treated with varix ligation and one was treated with splenectomy after the failure of bleeding control. One patient underwent a liver transplantation due to severe symptoms of portal hypertension. The prognosis of all the patients was excellent. Microscopically, the portal tracts were variably fibrotic, and the portal veins in them were sclerotic, obliterated or dilated in 7 cases; pathologic abnormalities were absent in 1 case. Cirrhosis was absent in all cases, while septal fibrosis was present in one resected liver.
CONCLUSIONS
IPH is a minor cause of portal hypertension. However, a liver biopsy to show the subtle portal vascular changes and fibrosis in patients who have the clinical symptoms of portal hypertension is important for making the diagnosis of IPH.

PDGF-R alpha Expression in Preneoplastic and Neoplastic Hepatocellular Lesions: A Rat Model N-nitrosomorpholine Stop Experiment.: Su Jin Kim, Kyoung Tae Kim, Jin Sook Jeong; Korean J Pathol. 2006;40(5):354-360.

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Abstract PDF: BACKGROUND
N-nitrosomorpholine (NNM) is a genotoxic hepatocarcinogenic agent. Preneoplastic and neoplastic hepatocyte lesions were induced in rats by oral exposure to NNM (200 mg/L) in a stop model experiment. Platelet-derived growth factor receptor (PDGF-R) is a tyrosine kinase receptor that works with PDGF, stimulating cellular growth and proliferation. The present study was designed to determine the role of PDGF-R alpha expression in hepatocellular neoplasms and precursors.
METHODS
Seventeen rats out of a starting number of 30 died. From the fifth week until the 24th week one or two rats were evaluated. Preneoplastic single cells or foci, foci of altered hepatocytes (FAH) hepatocellular adenomas (HCA) and hepatocellular carcinomas (HCC) were studied histologically, and the expressions of GSTp and PDGF-R alpha by immunohistochemistry.
RESULTS
At the fifth week, GSTp +single cells showed PDGF-R alpha expression (20.8+/-5.8%). At the sixth week, GSTp +single cells, located at periportal areas, co-expressed PDGF-R alpha (43.4+/-9.6%). Over the next several weeks periportal hepatocytes showed weaker PDGF-R alpha expression but no GSTp. GSTp+FAH, and all HCA, demonstrated no PDGF-R alpha expression. However, nine out of 10 (90%) HCC showed PDGF-R alpha expression.
CONCLUSIONS
These data showed that there were two peaks of PDGF-R alpha expression, and suggest that the earlier expression is related with the response to NNM-induced hepatocyte toxicity, and that the later response is associated to malignant transformation.

Immunohistochemical Characteristics of Kaposi Sarcoma and its Mimicries.: Kyoung Bun Lee, Hye Seung Lee, Hee Eun Lee, So Yeon Park, Jin Haeng Chung, Gheeyoung Choe, Woo Ho Kim, Kye Yong Song; Korean J Pathol. 2006;40(5):361-367.

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Abstract PDF: BACKGROUND
The differential diagnosis of Kaposi sarcoma includes many disease that range from benign disease to malignant tumors. However, little information is available about the immunohistochemical characteristics of Kaposi sarcoma.
METHODS
The expressions of 13 various proteins (HHV-8 LNA-1, Ki-67, bcl-2, p53, CD31, CD34, factor VIII, D2-40, vimentin, SMA, S-100, EMA, and c-kit) were evaluated immunohistochemically in 49 vascular tumors including 16 Kaposi sarcomas, 8 angiosarcomas, 2 hemangioendotheliomas, and 23 benign vascular tumors with using the tissue array method.
RESULTS
All 16 cases of Kaposi sarcoma showed nuclear staining for HHV-8 LNA-1, whereas all the cases of angiosarcoma and benign vascular lesions were negative for HHV-8 LNA-1 (p<0.001). All Kaposi sarcoma were positive for D2-40, which is a marker of lymphatic differentiation, but 25% of the benign vascular lesions and 30.4% of the angiosarcoma were positive for D2-40 (p<0.001). The mean proliferation index as assessed by Ki-67 immunostaining revealed no difference between the benign and malignant vascular lesions (p>0.05). No Kaposi sarcoma showed a bcl-2 expression, but 62.5% of the angiosarcomas and 21.7% of the benign vascular tumors had bcl-2 expressions (p=0.005).
CONCLUSIONS
Immunohistochemical detection of HHV-8 LNA-1 and D2-40 are useful tools to differentiate Kaposi sarcoma from other vascular tumors.

Case Reports

A Case of Arteriovenous Hemangioma Involving the Submandibular Gland: A Case Report.: Jai Hyang Go; Korean J Pathol. 2006;40(5):368-369.

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Abstract PDF: Hemangioma in the submandibular gland is extremely rare. It is mostly cavernous in the subtype found in adults. A case of arteriovenous hemangioma occurred in a 60-year old male patient. Oropharyngeal computed tomography revealed an ill-defined, poorly enhanced mass that involved the plastyma muscle. The excised mass was composed of large numbers of dilated blood vessels, mostly veins, with a peripheral rim of non-neoplastic salivary gland tissue. Small numbers of arteries were also admixed. Elastic staining revealed communications of the arteries and veins, which confirmed the diagnosis. Local recurrence is common in arteriovenous hemangioma because of the difficulties in achieving a complete excision, so pathologic diagnosis of this subtype is important in case of hemangioma.

Pediatric Adrenal Cortical Neoplasm with Histologic Malignancy: A Case Report with Review of Literature.: So Hyung Park, Daeyeon Kim, Gyungyub Gong; Korean J Pathol. 2006;40(5):370-372.

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Abstract PDF: Adrenal cortical neoplasm, especially carcinoma, is extremely rare in pediatric patients. We describe here a rare pediatric case of adrenal cortical neoplasm. A 2-year-old girl presented with an enlarged clitoris. The other physical findings and laboratory tests were nonspecific. The magnetic resonance imaging showed a 4 cm-sized heterogeneously enhancing soft tissue mass with calcification in the left adrenal gland. The mass was removed by laparoscopic operation. Grossly, several fragments of reddish tan soft tissue were present, and they weighed 19 gm in total. Microscopically, there were capsular invasion, diffuse/solid growth pattern with focal necrosis, high cellularity, cytoplasmic eosinophilia, marked nuclear pleomorphism, high N/C ratio, prominent nucleoli, atypical mitotic figures and calcifications, which all suggested adrenal cortical neoplasm of histologic malignancy. On immunohistochemistrical staining, there were positive reactivities to pancytokeratin, cytokeratin 7/20, CEA, inhibin and p53. The Ki-67 labeling index was about 6%. All these findings were indicative of adrenal cortical neoplasm of histologic malignancy.

Solitary Cutaneous Reticulohistiocytoma On the Upper Lip: A Case Report.: Jae Wang Kim, Hyun Wook Kang; Korean J Pathol. 2006;40(5):373-376.

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Abstract PDF: Reticulohistiocytosis represents a rare spectrum of non-Langerhans cell histiocytosis: the solitary cutaneous form (reticulohistiocytoma), the diffuse or multiple cutaneous form without systemic involvement, and multicentric reticulohistiocytosis with systemic involvement. To the best of our knowledge, there have been relatively few reports in the literature of solitary cutaneous reticulohistiocytoma found on the lip. We report here on a case of solitary cutaneous reticulohistiocytoma in a 58-year-old male, who presented with an asymptomatic dome-shaped nodule adjacent to the upper lip. The histopathologic examination revealed a dense dermal infiltrate, that was composed predominantly of large oncocytic histiocytes and multinucleated giant cells with abundant granular eosinophilic cytoplasms, which had a "ground-glass" appearance.

Angiomatoid Fibrous Histiocytoma: A Case Report.: Kyungeun Kim, Jong Seok Lee, Kyung Ja Cho; Korean J Pathol. 2006;40(5):377-380.

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Abstract PDF: We report on a case of angiomatoid fibrous histiocytoma located deep in subcutaneous tissue of the left shoulder in an 11-year-old boy. An ovoid firm mass was slowly increasing in size for 5 months without any pain or tenderness. The tumor was grossly multicystic, with dense fibrous capsule and it measured 7.5 x 7.5 x 4.0 cm. The locules contained hemorrhagic fluid, and the inner surface was purplish brown and trabecular. The septal solid areas were cellular, and they consisted of histiocytoid spindle cells that were arranged in a storiform or fascicular pattern. The tumor cells showed immuno-positivity for CD99, CD68 and desmin. These findings were compatible with angiomatoid fibrous histiocytoma of an uncommon location.

Tonsillar Lymphangiomatous Polyp: Report of Two Cases.: Han Suk Ryu, Soo Young Jung, Jae Soo Koh, Seung Sook Lee; Korean J Pathol. 2006;40(5):381-384.

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Abstract PDF: Tonsillar lymphangiomatous polyp is an uncommon hamartomatous lesion that generally arises from the tonsillar surface, and it has rarely been reported in the medical literature. Because of the uncommon clinical and pathological features of these polyps, pathologists and clinicians may experience difficulty in correctly classifying them. We report herein two cases of lymphangiomatous polyp of the tonsil in a 49 year-old man and a 30 year-old man who both presented with a tonsillar mass of the palatine tonsil. Microscopically, there were protruding polypoid lesions that had a core of fibroadipose tissue with dilated multiple lymphatics and aggregated lymphoid tissue. Both patients have been stable since resection.

Traumatic Neuroma in the Pancreas Head Following Excision of Pseudocyst: A Brief Case Report.: Jeong Won Kim, Gawon Choi, Jeong Eun Hwang, Shin Kwang Kang, Duck Jong Han, Se J Jang; Korean J Pathol. 2006;40(5):385-388.

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Abstract PDF: We describe here a case of traumatic neuroma that developed in the pancreas head as a rare complication of pancreatic surgery for pseudocyst. A 50-year-old man presented with septic shock. The patient was a heavy drinker with history of operation for pancreatic pseudocyst 28 years ago. On the radiologic examinations, a poorly defined mass-like lesion was found in the uncinate process of pancreas, and it had features of chronic pancreatitis and a stricture of the distal common bile duct. Whipple's operation was performed due to the diagnosis of suspected pancreas head cancer. The pancreas revealed an ill-demarcated 4 cm sized firm mass with grayish white fibrotic cut surface in the head portion. On the microscopic examination, the mass was composed of haphazard proliferations of nerve fascicles in a fibrocollagenous matrix and this case was diagnosed as traumatic neuroma. Although traumatic neruoma is a rare cause of a pancreatic mass, it should be included as a differential diagnosis of pancreatic mass in patients with a history of pancreatic surgery.

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