Effect of Selective Cyclooxygenase 2 Inhibitor in TCDD Pre-exposed Thyroid Papillary Carcinoma Cell Line

BACKGROUND: Cyclooxygenase 2 (COX-2) is related to carcinogenesis and progression of cancer. COX-2 has been detected in thyroid cancer. This suggests that COX-2 inhibitor may be useful to control the growth of thyroid cancer cells as well as the progression of thyroid cancer. Tetrachlorodibenzodioxin (TCDD), acting as an inflammatory cytokine, directly induces the expression of COX-2. We examine whether TCDD controls the effect of COX-2 inhibitor on thyroid cancer cells. METHODS: The effects of TCDD and celecoxib on thyroid papillary carcinoma cell line (SNU790) were examined using cell proliferation and fluorescence-activated cell sorting analysis. Western blot analysis was performed to determine the expressed COX-2 levels and the cell cycle-related proteins. The matrix metalloproteinase-2 (MMP-2) expression and gelatinolytic activity were examined using real time-polymerase chain reaction and zymography. RESULTS: TCDD directly induced the growth of SNU790 and the expression of cyclin D1, cyclin A, cyclin E, p21 and COX-2. Celecoxib suppressed the growth of SNU790 and the expression of cyclin D1 and cyclin E. Celecoxib reduced the MMP-2 expression and the gelatinolytic activity, but those effects were decreased in the SNU790 by either pre-treatment with TCDD or co-treatment with TCDD and celecoxib. CONCLUSIONS: Celocoxib effect is directly reduced depending on the exposure to TCDD. TCDD exposure should be considered in the treatment with Celecoxib.

PREFACE

No abstract available.

Development of the Korean Academy of Medical Sciences Guideline for Rating Physical Impairment

Systematic and effective welfare for the disabled is possible when there are scientific and objective criteria demonstrating either presence or severity of the impairment. We need our own scientific criteria suitable for our culture and society, since the impairment is influenced by them. In 2007, we established the Developing Committee of Korean Academy of Medical Sciences (KAMS) Guideline for Impairment Rating under KAMS supervision. We included all fixed and permanent physical impairments after a sufficient medical treatment. The impairment should be stable and medically measurable. If not, it should be reevaluated later. We benchmarked the American Medical Association Guides. The KAMS Guideline should be scientific, objective, valid, reasonable and practical. In particular, we tried to secure objectivity. We developed the KAMS Guideline for Impairment Rating.

Hepatoid Thymic Carcinoma: A Case Report

We report here on a rare case of hepatoid thymic carcinoma in a 34-year-old man. The patient complained of a high fever and headache, and a 6.6cm-sized anterior mediastinal mass was found on chest computed tomography (CT). There was no hepatic mass seen on abdominal CT. The resected mass consisted of epithelioid cells with abundant eosinophilic cytoplasm, pleomorphic vesicular nuclei and prominent nucleoli, and the mass was surrounded by thymic tissue. The tumor cells were immunopositive for cytokeratin 7, alpha-1-antitrypsin, hepatocyte staining, and epithelial membrane antigen, but they were negative for CD5, alpha-fetoprotein (AFP) and placental alkaline phosphatase, and this all led to a diagnosis of hepatoid thymic carcinoma rather than hepatoid yolk sac tumor. This entity should be included in the differential diagnosis of epithelioid thymic tumors.

The Author Respond

No abstract available.

Primary Pulmonary Ewing's Sarcoma/Primitive Neuroectodermal Tumor in a 67-year-old Man

Extraskeletal Ewing's sarcoma (EES) is a branch of neuroectodermal tumor (PNET), which is very rare soft tissue sarcoma. We report a case of EES/PNET arising is the lung of a 67-yr-old man. Computed tomography, bone scintigraphy, and positron emission tomography confirmed the mass to have a primary pulmonary origin. The mass showed positive reactivity in the Periodic Acid Schiff (PAS) stain and MIC-2 immunoreactivity in immunohistochemical stain. Fluorescence in situ hybridization (FISH) was performed, which revealed an EWSR1 (Ewing sarcoma breakpoint region 1) 22q12 rearrangement. The diagnosis was confirmed both pathologically and genetically. The mass lesion was resected, and the patient is currently undergoing chemotherapy.

Metastatic Medullary Carcinoma of Thyroid to Breast; A Case Initially Diagnosed as Primary Invasive Lobular Carcinoma: A Case Report

Metastasis to the breast from medullary carcinoma of the thyroid is extremely rare. We report a case of metastatic medullary carcinoma of the thyroid which presented as multiple breast masses with ipsilateral axillary lymphadenopathy in a 48-year-old woman. Six years ago, she underwent total thyroidectomy and neck dissection because of palpable neck masses, with a diagnosis of medullary thyroid carcinoma. Histological features of breast masses showed single- file or linear-cord arrangements, with plasmacytoid appearance, and the initial diagnosis was invasive lobular carcinoma. She underwent modified radical mastectomy. The tumor cells were diffusely positive for E-cadherin, calcitonin and thyroid transcription factor-1 (TTF-1) and were metastatic medullary carcinoma of thyroid. In the patients with a history of medullary carcinoma of the thyroid, a careful examination is necessary for a breast mass composed of solid and cord-like clusters of small round to ovoid cells with plasmacytoid appearance. Immunohistochemical staining for E-cadherin, calcitonin and TTF-1 could be helpful for differential diagnosis.

Chondroblastoma in a Distal Phalanx of the Great Toe: A Case Report / 대한정형외과학회잡지

A chondroblastoma is a relatively rare benign bone tumor that is typically encountered in the epiphysis. The authors describe a case of a chondroblastoma arising in the great toe. An 82-year-old woman presented with pain over her left great toe with a 1 year duration. The radiographs showed an expansile osteolytic lesion with cortical thinning and coarse trabeculation that replaced the distal phalanx of the left great toe. An incisional biopsy and curettage were performed. Histologically, the tumor consisted of uniform, round to polygonal cells with clear to slightly eosinophilic cytoplasm and round to ovoid nuclei, mimicking chondroblasts, intermingled with osteoclast-like giant cells.

Fine Needle Aspiration Cytology of Extranodal Marginal Zone B cell Lymphoma with Abundant Plasma Cells and Eosinophilic Histiocytes in Parotid Gland / 대한세포병리학회지

The authors present the fine needle aspiration cytology (FNAC) cytologic findings of a case of extranodal marginal zone B cell lymphoma (MZBCL), which featured abundant plasma cells and eosinophilic histiocytes arising in both parotid glands. A 49-year-old female presented with palpable masses in both parotid glands. She had been suffering from systemic lupus erythematosus and rheumatoid arthritis. The lesions were evaluated by FNAC and smears showed a small number of clusters of oncocytic cells with abundant eosinophilic granular cytoplasm and small nuclei, intermixed with small to medium-sized lymphoid cells containing round to lobulated nuclei, which suggested Warthin's tumor. Some of lymphoid cells had a plasmacytoid appearance, and some scattered large cells contained a large amount of eosinophilic cytoplasm. Bilateral superficial parotidectomy was performed and a histopathologic study indicated MZBCL with abundant plasma cells, intermixed with eosinophilic histiocytes. The presence of oncocytic cells and a mixture of lymphoid and plasma cells indicates Warthin's tumor, but the cytologic features of a relatively monotonous small to medium-sized lymphoid infiltrate suggest the possibility of MZBCL in the clinical setting of an FNAC study performed on a patient suffering from a connective tissue disease.

Expression of Heregulin and ErbB Family Proteins in Gastric Adenocarcinomas: Correlation with Clinopathologic Prognostic Factors

PURPOSE: Heregulin is a natural ligand for erbB3 and erbB4. However, very little is known about their roles in the gastric cancer. This retrospective study was performed to evaluate the frequencies of heregulin and erbB family protein expression and to compare their expressions with clinicopathologic parameters. MATERIALS AND METHODS: Immunohistochemical expressions of heregulin and erbB family proteins were examined with tissue micro-array slides. A total of 251 gastric adenocarcinomas were classified as early cancers and advanced cancers and as having and not having lymph node metastases. RESULTS: The positive rates of the heregulin, erbB1, erbB2, erbB3, and erbB4 protein stainings were 64%, 68%, 6%, 88%, and 76%, respectively. Intestinal type gastric adenocarcinomas showed higher expression of heregulin, erbB2, erbB3, and erbB4 proteins. Heregulin and erbB4 proteins showed lower expressions in advanced gastric carcinomas. However, erbB2 protein showed higher expression in advanced gastric carcinomas. The protein expressions of heregulin and erbB family proteins showed no relationship with survival rate. Co-expression groups of heregulin and erbB3 proteins or heregulin and erbB4 proteins showed higher expressions in intestinal type adenocarcinomas and early gastric carcinomas. CONCLUSION: Heregulin, erbB3, and erbB4 proteins may play a role in the early stage of adenocarcinomas.

Mucin Expression According to the Progression of Gastric Carcinomas

PURPOSE: Alteration of the mucin profile has been known to be related with the progression of the gastric cancers. This study was intended to evaluate the expression of MUC proteins in gastric cancers and assess the differences in their expressions and the tumor depth, histological classification, lymph node metastases, and the survival of gastric cancers patients. METHODS: A total of 251 gastric adenocarcinomas were classified using tumor progression as early cancers and advanced cancers, either with or without lymph node metastases. The immunohistochemical expressions of MUC1, MUC2, MUC5AC, and MUC6 were examined using tissue array slides. RESULTS: Intestinal type of gastric adenocarcinomas showed higher expressions of MUC1 and MUC2 (P=0.004, P=0.028), but no statistical relationship was found with the expressions of MUC5AC and MUC6. MUC2, MUC5AC, and MUC6 showed progressively lower expressions in relation to advanced lesions and lymph node metastases, ; however, MUC1 showed higher expressions according to tumor progression. Patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those not expressing MUC1 (P=0.0134). Also, those patients expressing lower levels of MUC5AC and MUC6 showed poorer survival rates (P=0.000, P=0.0213). The expression of MUC2 showed no relationship with survival rate. CONCLUSION: The present study suggests that study of mucin profile might be a useful prognostic factor for predicting the outcome of gastric cancer patients.

Gastrointestinal Stromal Tumors in Koreans: It's Incidence and the Clinical, Pathologic and Immunohistochemical Findings

Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p=0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p= 0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.

Liposclerosing Myxofibrous Tumor in Tibia: A Case Report and Review of the Literature

Liposclerosing myxofibrous tumor (LSMFT) is a benign fibro-osseous lesion that is characterized by a complex mixture of histologic elements, including its fibrous dysplasia-like features and its lipoma, myxofibroma, xanthoma and pseudo-Paget's bone patterns. However, this lesion is considered by some researchers as a variant of fibrous dysplasia or as the non-specific end result of degenerative change, while it is considered by others as a definite clinicopathologic entity. Here, we report on a case of LSMFT occurring in tibia, which is a very uncommon location for this tumor, and we review the related literatures. The case presented here shares features with those described for LSMFT, except for the location of this tumor. We believe that more studies on a larger scale that compare LSMFT with other benign bone lesions, including fibrous dysplasia, are required to clarify the origin and behavior of this lesion.

The Usefulness of Concomitant High-Risk Human Papillomavirus Test and Colposcopy in Combination with the Papanicolaou Test in ASCUS Patients / 대한세포병리학회지

The objective of this study was to ascertain whether or not the high-risk human papillomavirus(HPV) test, when coupled with Papanicolaou(Pap) smears, would prove useful in the screening and management of patients in whom abnormal Pap smear results had been obtained. Concomitant high-risk HPV detection using the hybrid capture II test and colposcopy with a Pap smear were performed with 176 patients, all of whom had been screened for both cervical carcinoma and precancerous lesions. We concomitantly performed colposcopies on these patients. Upon the follow-ups, the histologic diagnoses of these patients were confirmed via either biopsy or hysterectomy. The rate of high-risk HPV detection was correlated with cytologic diagnoses and colposcopic findings. The group composed of the high-risk HPV-positive ASCUS patients exhibited a 55.7% rate of cervical intraepithelial neoplasia(CIN), a significantly higher rate than the 7.5% result obtained in the high-risk HPV- negative ASCUS group. HPV test showed high sensitivity(87%) and low specificity (62.6%) in detection of CIN and colposcopy also showed high sensitivity (88%) and low specificity(22%). Any combination of these tests improve sensitivity, but not specificity. High-risk HPV tests, when coupled with Pap smears, constituted a useful triage approach with regard to colposcopy-directed biopsies in patients in whom a cytologic diagnosis of ASCUS had been rendered.

Prevalence and Clinicopathologic Features of Mucinous Cystic Tumor and Intraductal Papillary Mucinous Tumor of Pancreas in Korea

BACKGROUND: Mucin producing cystic neoplasms, such as mucinous cystic tumor (MCT) and intraductal papillary mucinous tumor (IPMT) of the pancreas, are uncommon but become increasing in their incidences. The pathologic classification and biologic potential of these neoplasmsremain the subject of controversy. METHODS: The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists analyzed the clinicopathologic characteristics of 85 casesof MCT and 72 cases of IPMT and examined the expression patterns of p53, CEA and MUC1. RESULTS: IPMT was located largely in the head, and showed connection with the main pancreatic duct (MPD, 68.1%), no ovarian-like stroma (0/72), and presence of intervening intratumoralnormal or atrophic parenchyma. On the other hand, MCT was located largely in thetail (73%), and showed common ovarian-like stroma (66/80), rare connection with the MPD(7/85) and no intervening pancreatic parenchyma. CEA and p53 immunoexpressions weresignificantly increased from adenoma through borderline to carcinoma, but MUC 1 was expressedonly in the invasive carcinoma among cases of MCT and IPMT. CONCLUSIONS: The tumorlocation, ovarian-like stroma, connection with the MPD and intratumoral intervening nonneoplastictissue were helpful in the differential diagnosis between IPMT and MCT. CEA and p53expressions can be indicators of malignancy, while MUC 1 expression can indicate invasion.

Expression of Survivin and KAI-1 in Gastric Adenocarcinomas

PURPOSE: The aim of this study was to investigate the impact of survivin expression and the decrease or loss of KAI-1 on the clinical stage and the survival rate in gastric adenocarcinomas. MATENRIALS AND METHODS: Expressions of survivin and KAI-1 were immunohistochemically determined in 40 cases of gastric adenocarcinomas. The survivin and KAI-1 expressions were also analyzed by using western blots in 14 cases among them. RESULTS: Resected gastric cancer specimens from 40 patients (intestinal type: 15 cases and diffuse type: 25 cases) were evaluated immunohistochemically. Survivin protein expressions were significantly higher in diffuse types (P=0.03) and in advanced clinical stages (UICC TNM II and III, P=0.02). In contrast, a decrease or loss of KAI-1 expression had no statistically significant correlation with the Lauren classification or the clinical stage. Survivin protein positivity was associated with an unfavorable prognosis. Decrease or loss of KAI-1 was associated with a shorter disease free survivial rate (P<0.01). The western blot data (n=14) indicated that neither survivin protein over-expression nor KAI-1 down-expression had an significant correlation with the Lauren classification or the clinical stage. CONCLUSION: In gastric carcinomas, survivin over-expression and decrease or loss of KAI-1 were associated with unfavorable prognosis, being independent prognostic factors along with the clinical stage and the disease free survival rate.

Prognostic Significance of KAI-1 and Survivin Expressions in Ovarian Epithelial Carcinomas / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the expressions of KAI-1 and survivin, and to investigate their correlation with the clinical stage and survival rate of patients with ovarian carcinomas. MATERIALS AND METHODS: The expressions of survivin and KAI-1 were immunohistochemically determined in 54 serous and mucinous ovarian adenocarcinomas and borderline malignancy tumors. 10 of the 54 cases were also analyzed for the expressions of survivin and KAI-1 using western blot. RESULTS: The down-regulation of the expression of KAI-1 was observed by immunohistochemical staining (IHC) in 53.7% of the ovarian cancers, and a negative reaction in 50% by the western blot analysis. From the IHC, the survivin expression was positive and strongly positive in 51.9 and 18% of the ovarian cancers, respectively. From the western blot analysis, 10% of the ovarian cancer showed positive reactions. The down- regulation of the KAI-1 expression was significantly correlated with the clinical stage (p=0.001) and disease free survival rate (p<0.001), but not with the histological type. The expression of survivin was not correlated with the clinical stage or histological type. However, the patients with a negative survivin expression had a significantly longer disease survival rate than those with a strong positive expression. CONCLUSION: The down- and up-regulation of the KAI-1 and survivin, respectively, might be independent prognostic factors in human ovarian carcinomas.

The First Human Case of Hepatic Dirofilariasis

Most of human dirofilariasis are pulmonary or subcutaneous infections, but there have been a few reports of human dirofilariasis in unusual sites, such as large vessels, mesentery, peritoneal cavity, and spermatic cord. We present the first case of human hepatic dirofilariasis, which was surgically diagnosed. A 39-yr-old man without any evidence of systemic symptom was found incidentally to have a hepatic nodule during routine physical check-up. The histologic findings of the resected lesion showed a granulomatous lesion with central necrosis containing up to 35 transverse sections of a nematode, ranging 30-80 micrometer in diameter. Thin (1.5-5 micrometer) cuticle with transverse striations surrounded polymyarian and muscle bundles occupied a sixth of both sides of outer body cavity. Central portion of the body cavity was occupied with an intestine-like tubular structure and a larger reproductive tube. These microscopic findings were consistent with degenerated Dirofilaria immitis. Antibody test by enzyme-linked immunosorbent assay for patient serum reacted positively against adult D. immitis antigen.

Role of Angiogenesis and Expression of Vascular Endothelial Growth Factor in Mouse Skin Carcinogenesis

BACKGROUND: Angiogenesis is crucial for many biological processes such as embryogenesis, cyclic changes in the endometrium and wound healing. It is also critical for the growth, invasion and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) acts as a mitogen for endothelial cells and is expressed by the presence of various tumor cells. The objective of this study is to evaluate if angiogenesis is involved in the mouse skin carcinogenesis and if VEGF is related to angiogenesis. METHODS: We induced premalignant and malignant lesions on mouse (BALB/c) skin using the two stage chemical carcinogenesis moedl, DMBA (7,12-dimethylbenzanthracene) initiation and TPA (tetra decanoyl-phorbol-acetate) promotion. And we analysed the microvessel densities (MVD) and expression of VEGF in various stages of premalignant and malignant lesions by immunohistochemical studies. RESULTS: Squamous papillomas, keratoacanthoma, dermatofibroma, and squamous cell carcinomas were developed in 20 weeks. There were no differences in the incidence of benign and malignant tumors between 10-week and 20-week promotion groups. There were significant increases in MVD from normal and hyperplastic skin through premalignant lesion to invasive squamous cell carcinoma (p<0.0005). But the degree of VEGF expression neither correlated with neither MVD nor the tumor groups. CONCLUSIONS: Increased angiogenesis begins from the hyperplastic stage. VEGF produced by tumor cells may not play major roles in the angiogenesis in the two stage chemical carcinogenesis model of the mouse skin.

Detection of Micrometastases of Breast Cancer by Immunohistochemical Analysis of Cytokeratin / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Axillary lymph node metastases are the single most important predictor of overall survival in patients with breast cancer. Micrometastases are defined by the American Joint Committee on Cancer as tumor foci less than or equal to 2 mm in greatest dimension. Recently, up to 30% of breast cancer patients were reported to have micrometastases. In this paper, to assess the rate of micrometastases in patients with stage I breast cancer, we attempted to determine the most useful marker of the micrometastases in node negative cases by routine histopathologic examination of regional lymph nodes and comparison of the results with the influencing factors on prognosis. MATERIALS AND METHODS: We performed immunohisto chemical staining for pancytokeratin, cytokeratin 7, cytokeratin 20 and CEA to identify which protein was the most useful marker for the detection of micrometastases in 86 node negative cases and determined the correlation between histological and clinical data. RESULTS: A total of 5 lymph nodes in 5 separate cases showed micrometastases among the total 1,296 lymph nodes and 86 cases. The rates of micrometastases of lymph nodes and cases were 0.38% and 5.8%, respectively. The tumor type of micrometastasis was infiltrating ductal carcinoma in all cases. None of the microme tastases cases showed any relationship with tumor grade, tumor size, expression of ER and PR, patient survival rate or recurrence rate. The most useful marker to detect micrometastases was pancytokeratin. CONCLUSION: The results of this study indicate that micrometastasis of axillary lymph nodes does not carry any independent prognostic significance.