Journal of Pathology and Translational Medicine

Volume 40(2); April 2006

Original Articles

Immunohistochemical Expression of the Sodium/Iodide Symporter in Patients with Primary Lung Cancer.: Hyoun Wook Lee, Do Young Kang, Phil Jo Choi, Doo Kyung Yang, Ki Nam Kim, Kyung Eun Lee, Mee Sook Roh; Korean J Pathol. 2006;40(2):81-85.

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Abstract PDF: BACKGROUND
The sodium/iodide symporter (NIS) is a membrane glycoprotein that facilitates the uptake of iodine by thyroid follicular cells. Although the use of radioiodide is essential for the diagnosis and treatment of thyroid diseases, few studies have been conducted to investigate the use of NIS-mediated radioiodide accumulation in lung cancer. We evaluated the expression of NIS by immunohistochemistry in order to examine the diagnostic or therapeutic feasibility of using radioiodide in the treatment of primary lung cancer.
METHODS
Immunohistochemistry for NIS was performed in 139 lung cancers. The expression pattern of NIS was compared with the clinicopathological characteristics of the tumors.
RESULTS
NIS immunoreactivity was detected in 75 (54.0%) of the 139 cases. Twenty-three (37.7%) of the 61 squamous cell carcinomas, 49 (76.6%) of the 64 adenocarcinomas, 2 (40.0%) of the 5 small cell carcinomas, and 3 (33.3%) of the 9 other carcinomas showed positive NIS immunoreactivity. The expression of NIS was significantly associated with the histologic type (p<0.001), but it did not correlate with tumor size, lymphovascular invasion or lymph node metastasis.
CONCLUSIONS
The presence of NIS was detected in lung cancer tissue using immunohistochemistry. Lung cancer potentially could be targeted with radioiodide for both diagnosis and treatment, especially in cases of adenocarcinoma.

Usefulness of Galectin-3, Cytokeratin 19, p53, and Ki-67 for the Differential Diagnosis of Thyroid Tumors.: Moon Il Park, Dae Young Kang; Korean J Pathol. 2006;40(2):86-92.

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Abstract PDF: BACKGROUND
The expressions of galectin-3, cytokeratin 19, p53, and Ki-67 in papillary carcinoma (PC), follicular carcinoma (FC), follicular adenoma (FA), and nodular hyperplasia (NH) are characteristic for the differential diagnosis between benign and malignant thyroid tumors.
METHODS
The expressions of the four markers were evaluated in PC (n=37), FC (n=12), FA (n=22), and NH (n=23) by immunohistochemical staining.
RESULTS
Statistical analyses revealed that galectin-3 was significantly expressed in the malignant tumor cells of PC and FC, while CK19 was expressed only in PC.
CONCLUSION
These results show that galectin-3 is useful in differential diagnosis between malignant and benign thyroid lesions, especially between FC and FA in the patients over 20 years old, and indicate that CK19 is valuable in differentiating between follicular variant of PC and FC and between PC and papillary area of nodular hyperplasia.

Nicotinamide Reduces the Infarct Volume in a Rat Model of Transient Middle Cerebral Artery Occlusion.: Min Sup Lee, Young Jun Ahn, Ki Young Choi, Gu Kang, Seong Sik Kang, Il Young Cheong, Kun Jai Lee, Keun Woo Kim; Korean J Pathol. 2006;40(2):93-102.

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Abstract PDF: BACKGROUND
Cerebral ischemia depletes ATP and causes irreversible tissue injury. Nicotinamide is a precursor of NAD+ and it is also a poly (ADP-ribose) polymerase (PARP) inhibitor that increases the neuronal ATP concentration and so protects against stroke. Therefore we examined whether nicotinamide could protect against cerebral ischemia by using a model of transient middle cerebral artery occlusion (MCAO) (reperfusion 2 h post ischemia) in Sprague-Dawley rats.
METHODS
Nicotinamide (500 mg/kg) or normal saline was administered intraperitoneally 24 and 0 h before and after MCAO, respectively. The infarction volumes were determined with triphenyltetrazolium chloride staining 24 h after reperfusion. The nitrotyrosine, PAR polymer and PARP-1 expressions were examined by immunohistochemistry with using brain slices obtained from the rats that were sacrificed at 0, 15, 30, 60 and 120 min after reperfusion.
RESULTS
The infarction volumes were significantly attenuated (21.8%, p<0.05). The nitrotyrosine expressions were increased at 0, 15 and 30 min, and those expressions for PARP polymer and PARP-1 were increased at 60 and 120 min, respectively. Nicotinamide partly reduced the expressions for nitrotyrosine and PAR polymer except for PARP-1.
CONCLUSIONS
These results suggest that nicotinamide may attenuate ischemic brain injury through its antioxidant activity and the inhibition of PARP-1.

Enhanced CD24 Expression in Colorectal Cancer Correlates with Prognostic Factors.: Yoon La Choi, Hua Xuan Yan, Sang Jeon Lee, Seon Mee Park, Wun Jae Kim, Hee Jin Kim, Seok Hyung Kim; Korean J Pathol. 2006;40(2):103-111.

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Abstract PDF: BACKGROUND
CD24 was originally described as a B cell-specific marker, however its aberrant expression in various solid tumors has recently been reported. Our objective was to determine the pattern and extent of the CD24 expression in colorectal cancer and its related lesions, and to clarify its correlation with clinico-pathological parameters and especially those associated with patients' prognoses.
METHODS
A total of 307 colorectal cancers and the related lesions (150 carcinomas, 30 high-grade adenomas, 49 low-grade adenomas, 41 hyperplastic polyps, and 37 normal colorectal epithelia) were immunohistochemically analyzed by treating CD24 monoclonal antibody onto tissue embedded paraffin blocks.
RESULTS
CD24 expression was very rarely observed in the normal epithelia, hyperplastic polyps, and low-grade adenomas; however, in high-grade adenomas, the CD24 expression was shown to be mildly increased in the cytoplasm (13.3%). In carcinomas, the CD24 expression was increased substantially in both the membrane (38.0%) and the cytoplasm (44.7%). The expression of CD24 in the membrane was positively correlated with tumor size (p<0.01). The CD24 expression in the cytoplasm was positively correlated with several unfavorable parameters, including a larger tumor size (p<0.01), a higher tumor grade (p<0.01), a higher rate of tumor invasion (p<0.05), and a higher pTNM stage (p<0.05).
CONCLUSION
High levels of CD24 expression in the membrane and cytoplasm were characteristic in colorectal cancer, and the cytoplasmic CD24 expression was correlated with several unfavorable clinical parameters.

Fascin-1 Protein Expression in Gastric Carcinoma.: Seoung Wan Chae, Jin Hee Sohn; Korean J Pathol. 2006;40(2):112-117.

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Abstract PDF: BACKGROUND
Fascin-1 is a globular cross-linking and actin bundling protein that provides mechanical support to cellular protrusions and cell motility. The expression of fascin in epithelial neoplasms has been recently reported, but its exact mechanism in cancer is unknown. The purpose of this study was to assess the expression of fascin and its relationship with the clinicopathologic parameters and the other tumor markers in gastric carcinoma.
METHODS
Immunohistochemical stainings for fascin, c-erbB-2, p53 and Ki-67 labeling index were performed in 62 gastric carcinoma specimens.
RESULTS
Fascin-1 protein was not expressed in the normal gastric glandular epithelial cells. It had an expression in 35.5% of the gastric adenocarcinomas. The fascin-1 expression in carcinoma was slightly increased in the well to moderately differentiated tumors compared with the poorly differentiated tumors. The fascin-1 expression was correlated with the c-erbB-2 protein expression. There was no significant correlation with the clinicopathologic factors such as tumor size, nodal metastasis, pathologic stage, p53 protein expression and Ki-67 labeling index.
CONCLUSIONS
This study reveals the possibility that the fascin-1 protein expression in gastric carcinoma may be closely linked with the c-erbB-2 protein expression. However, further study on fascin-1 and c-erbB-2 protein at the cellular level and their clinical relevance is needed.

Pathologic Comparative Studies on the Protective Effects by Panax Ginseng and Panax Quinquefolium for Treating 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced Toxicity in Male Rats.: Dae Young Kang, Moon Il Park, Sun Young Na, Jae Joon Wee; Korean J Pathol. 2006;40(2):118-127.

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Abstract PDF: BACKGROUND
Panax ginseng is known to decrease the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular toxicity. Thus, we aimed to reveal the differences between Panax ginseng and Panax quinquefolium extract for their effects on TCDD-induced toxicity.
METHODS
Forty rats were divided into four groups; the control group, the TCDD only group, the TCDD plus Panax ginseng group, and the TCDD plus Panax quinquefolium-treated groups. Ginseng extract was given orally to rats from day one to twenty-one. TCDD was intraperitoneally administered to rats at a single dose of 50 microgram/kg on the seventh day. The pathologic changes were then examined. The changes of body weight, cholesterol and GOT in the serum were also examined.
RESULTS
The TCDD toxicity was prominent in the thymus, liver and testis. The thymus showed atrophy and an inverse pattern of lymphocyte density in the cortex and medulla. The liver revealed central necrosis with fatty changes. On electron microscopy, the seminiferous tubules showed destruction of the spermatogonia, clear spaces or vacuolar changes and degeneration in the Sertoli cells or germ cells. The above mentioned TCDD-induced changes were reduced in the rats that were administered with Panax ginseng, whereas Panax quinquefolium did not reduce these changes.
CONCLUSION
The protective effects of Panax ginseng on the TCDD-induced toxicity were more effective than those of Panax quinquefolium.

A High Thymidylate Synthase Expression is Related to Better Outcome for Advanced Gastric Cancer Patients Treated with 5-FU Chemotherapy after Curative Resection.: Mee Yon Cho, Sang Yeop Yi, Min seob Eom, Shu Peng Zhang, Hwan Sik Kim, Jong In Lee, Dae Sung Kim; Korean J Pathol. 2006;40(2):128-136.

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Abstract PDF: BACKGROUND
The expressions of thymidylate synthase (TS), E2F-1, pRb, and p53 are correlated with DNA synthesis. The significance of their expressions is still controversial for predicting the outcome of 5-fluorouracil (5-FU) therapy in the patients with advanced gastric carcinoma. Furthermore, their prognostic value in the metastatic lesions of gastric carcinoma has not yet been confirmed.
METHODS
To ascertain their prognostic value, we immunohistochemically analyzed the expressions of TS, E2F-1, pRb, and p53 in the primary tumors and the related metastatic lymph nodes, and we then compared the survival between the high and low expression group of each protein. Ninety four patients with advanced gastric carcinoma who were treated by complete resection and adjuvant 5-FU chemotherapy were analyzed.
RESULTS
The TS expression in primary tumors was significantly correlated with that of E2F-1. The expression of these genes showed no significant difference between the primary tumors and the metastatic lymph nodes except for E2F-1, which was significantly higher in the lymph node metastasis than in the primary tumors. After complete resection and 5-FU-based adjuvant chemotherapy, patients with a high TS expression in the primary tumors showed a longer survival than those patients having primary tumors with a low TS expression (p=0.0392).
CONCLUSION
A high TS expression in the primary tumors may be related to a better outcome for advanced gastric cancer patients who were treated with 5-FU chemotherapy after curative resection.

Case Reports

Gastrointestinal Stromal Tumors associated with Neurofibromatosis Type I: A Report of Two Cases.: Joo Heon Kim, Ock Seong In, Seong Kyu Lee, Haing Woon Baik, Seong Ho Kim, Dong Wook Kang, Kyung Hee Kim, Mee Ja Park, Yong Il Kim; Korean J Pathol. 2006;40(2):137-141.

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Abstract PDF: Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract, but this tumor is rarely seen in association with type 1 neurofibromatosis (NF-1). We report here on two cases of multiple GISTs of the small intestine that occurred in NF-1 patients. We also analyzed the mutations of c-kit exons 9, 11, 13 and 17 and the plateletderived growth factor receptor-alpha (PDGFRA) exons 12 and 18 in two GIST patients. Histologically, the NF-1-associated GISTs were similar to those of non-the NF-1 GISTs, but they characteristically revealed hyperplastic interstitial cells of Cajal around the GISTs. Immunohistochemically, these tumors showed strong co-expressions of CD117 and CD34. The molecular genetic analysis of the GISTs showed that all of the c-kit and PDGFRA exons that were analyzed in the GISTs of the two patients were the wild-type, suggesting a limited role for the c-kit and PDGFRA mutations in the tumorigenesis of NF-1-associated GISTs.

Composite Hemangioendothelioma: A Case Report.: Young Chae Chu, Suk Jin Choi, In Suh Park, Lucia Kim, Jee Young Han, Joon Mee Kim; Korean J Pathol. 2006;40(2):142-147.

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Abstract PDF: Composite hemangioendothelioma (CHE) is a recently described vascular tumor of low-grade malignancy. We report a case of CHE in an 18-year-old woman who presented with a 2-month history of an enlarging palpable mass in the left axilla. Grossly, the excised tumor was relatively circumscribed, nodular, firm, and soft. It measured 6.0 x 4.5 x 4.0 cm. The cut surface revealed a whitish gray solid area and a dark red to tan cystic area containing necrotic material. Histologically, the tumor demonstrated variably intermixed benign and malignant vascular components. The benign components showed features of an arteriovenous malformation, capillary hemangioma, spindle cell hemangioma and cavernous hemangioma. The malignant components were composed of areas resembling retiform hemangioendothelioma, epithelioid hemangioendothelioma, Kaposiform hemangioendothelioma, and angiosarcoma. The angiosarcoma component showed a mixed epithelioid and spindle shaped cell morphology with moderate differentiation. A nearly imperceptible transition between the benign and malignant components was noted.

Inflammatory Myofibroblastic Tumor of the Stomach: A Case Report.: Joon Mee Kim, In Suh Park, Lucia Kim, Suk Jin Choi, Jee young Han, Young Chae Chu, Kyoung Rae Kim; Korean J Pathol. 2006;40(2):148-150.

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Abstract PDF: Inflammatory myofibroblastic tumor of the stomach is a rare tumor-like, benign disease with an uncertain pathogenesis. A 15-year-old male presented with epigastric pain. Endoscopic ultrasonography revealed a 2.3 cm sized ovoid intramuscular mass in the lower body of the stomach at the lesser curvature. Histologically, the tumor was composed of smooth muscle actin positive- and vimentin positive spindle cells and there were a large number of lymphocytes, plasma cells and histiocytes in the fibrotic background. The spindle cells were also positive for ALK1, but negative for EBV in situ hybridization.

Follicular Lymphoma with Monoclonal Plasma Cell Differentiation: A Case Report.: Hyun chul Kim, Young Seok Lee, Jung woo Choi, Ae ree Kim, Bom Woo Yeom, Han kyeom Kim, In sun Kim; Korean J Pathol. 2006;40(2):151-155.

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Abstract PDF: We present a case of recurrent follicular lymphoma with an extensive plasma cell component involving infra-auricular lymph nodes in a 64 year-old woman. Immunohistochemical staining showed a strongly positive reaction of the follicles with CD20, bcl-2, bcl-6, CD10 and CD21 on the first biopsy specimen. The intrafollicular and interfollicular plasma cells showed monoclonality for IgG heavy chain and lambda light chain. The histological and immunohistochemical findings in the recurrent tumor were identical with those of the original. Discussion is focused on the importance of the differential diagnosis between reactive lymphoid hyperplasia and other lymphomas having plasmacytic differentiation.

Histiocytic Sarcoma of Rectum: A Case Report.: Moon Il Park, Kyu Sang Song, Dae Young Kang; Korean J Pathol. 2006;40(2):156-159.

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Abstract PDF: We present a case of a 44 year-old man with histiocytic sarcoma arising from the rectum. Histiocytic sarcoma is a rare type of malignant lymphoma, comprising less than 0.5% of all non-Hodgkin's lymphomas (NHLs). In this case, the tumor was a polypoid mass, measuring 2.5 x 2 cm. On microscopic examination, it was composed of many bizarre multinucleated cells and sheets of xanthomatous histiocytes. There were also areas with spindle cells arranged in a storiform pattern. Extensive metastases to regional lymph nodes were found, and combined adjuvant chemotherapy was administered after complete resection.

Adenosquamous Carcinoma of the Ampulla of Vater: A Report of Two Cases.: Da keun Lee, Cheol Keun Park, Geung hwan Ahn, Sung Ju Kim, Jin Seok Heo, Kyu Taek Lee, Sang hui Park, Kee Taek Jang; Korean J Pathol. 2006;40(2):160-164.

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Abstract PDF: Primary adenosquamous carcinoma of the ampulla of Vater is extremely rare. We report two cases of adenosquamous carcinoma of the ampulla of Vater in a 48-year-old female and an 80-year-old female patient. The gross appearance was a polypoid mass in both cases. Histologically, the majority of the two tumors was composed of squamous cell carcinoma with some intermingled glandular adenocarcinoma components in both cases. Squamous cell carcinomas showed an abrupt transition from the normal glandular epithelium or glandular adenocarcinoma. Although the two cases revealed duodenal wall invasion and lymph node metastasis was found in case 2, both patients are still alive at 19 and 46 months after surgery, respectively.

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