P2X7 Receptor Expression in Coexistence of Papillary Thyroid Carcinoma with Hashimoto's Thyroiditis

BACKGROUND: This study was aimed at investigating the relation of P2X7 receptor (P2X7R) expression with the clinicopathological features of papillary thyroid carcinoma (PTC) coexisting with Hashimoto's thyroiditis (HT). METHODS: We examined 170 patients (84, PTC with HT; 86, PTC without HT). P2X7R expression was examined by immunohistochemical methods. The staining intensity and patterns were evaluated and scored using a semi-quantitative method. RESULTS: The PTC with HT group was more likely to contain women and had less extrathyroid extension, lymph node (LN) metastasis, lymphovascular invasion, and recurrence than the PTC without HT group. Patients positive for P2X7R had significantly higher frequencies of lymphovascular invasion, extrathyroid extension, LN metastasis, and absence of HT. As shown by multivariate analysis, the expression of P2X7R was significantly higher if HT was absent and extrathyroid extension was present. In the PTC with HT group, the expression of P2X7R was significantly higher in patients with tumor multifocality, lymphovascular invasion, and extrathyroid extension. In the PTC without HT group, the expression of P2X7R was significantly higher in women and those having tumor multifocality. CONCLUSIONS: Coexistence of PTC with HT is associated with good prognostic factors, and P2X7R expression in PTC was correlated with poor prognostic factors and the absence of HT.

Rabies Post-Exposure Prophylaxis of Overseas Travelers in the International Travel Clinic of the National Medical Center from 2006 to 2012, Korea / 감염과화학요법

BACKGROUND: Rabies is an acute fatal viral disease generally transmitted from infected animals to humans through bites. It is distributed worldwide. The number of Korean people traveling to rabies-endemic countries and being bitten by infected animals has been increasing recently. Therefore, we investigated international travelers who received rabies post-exposure prophylaxis (PEP) at the National Medical Center (NMC) and compared the data with those of other clinics. MATERIALS AND METHODS: This study was a retrospective review of 106 patients who visited the International Travel Clinic of the NMC and received rabies PEP between July 2006 and December 2012. During that period, we used the Essen intramuscular regimen protocol. Complete rabies PEP was defined as 5 doses of rabies vaccination with or without rabies immunoglobulin (RIG) administration according to the World Health Organization guidelines. RESULTS: A total 106 cases documented within the period of 6 years were selected, including 10 children younger than 15 years and 96 older than 15 years. The mean age of the patients who received PEP was 33.4 years. Of the patients, 53 were male and another 53 were female. Most of the exposures occurred in Southeast Asia, predominantly from dog bites (71, 66.9%). The lower extremities were the most frequent site of exposure (37, 34.9%). All the patients began receiving rabies vaccination for prophylaxis after exposure, and 51 received rabies vaccination with RIG. Meanwhile, 74 cases (69.8%) initiated rabies vaccination overseas, but only 10 of them received RIG while overseas; the remaining 32 (30.2%) initiated rabies vaccination after returning to Korea. Within 7 days, all the children and 74 adults received their first rabies vaccination. Six adults initiated first rabies vaccination after 1 week. Eleven of the 106 patients stopped PEP before 5 doses, among whom 4 (1 child and 3 adults) discontinued vaccination after confirming that the biting animal remained healthy throughout 10 days of observation. None of the patients had been previously vaccinated against rabies. CONCLUSIONS: Most of the overseas travelers who visited our clinic after being bitten by suspected rabid animals received appropriate rabies PEP. However, the interval between exposure and first rabies vaccination was often delayed. Tourists who plan to travel in rabies enzootic regions need to be aware that prompt initiation of PEP is important to reduce the risk for developing human rabies.

Histopathologic Predictors of Lymph Node Metastasis and Prognosis in Tonsillar Squamous Cell Carcinoma

BACKGROUND: Risk factors for lymph node metastasis in tonsillar squamous cell carcinoma (TSCC) need to be established to determine the degree of surgery required to achieve high curative rates. However, little is known currently about the histopathological features predicting prognosis, specifically in TSCC. METHODS: This study included 53 patients who underwent surgical resection with neck dissection. Clinicopathological factors investigated included age, gender, alcohol use, tobacco consumption, tumor stage, adjacent structure involvement, cell differentiation, squamous dysplasia, in situ carcinoma associated with primary invasive cancer, carcinoma in situ skip lesions, necrosis, invasive front, depth of invasion, and lymphatic, muscle, or perineural invasion. RESULTS: Contralateral cervical metastasis was associated with higher T stages and soft palate invasion. Lymphatic and muscle invasion were associated with ipsilateral cervical metastasis. Advanced T stage, invasion to the base of tongue, and skip lesions were associated with decreased disease-free survival. Advanced T stage and skip lesions were associated with worse overall survival. CONCLUSIONS: Advanced T stage and soft palate invasion may predict a high risk of contralateral nodal metastasis. T stage and skip lesion are worse prognostic factors in TSCC and should be commented in pathology reports.

A Case of Cronkhite-Canada Syndrome with Esophageal Candidiasis

Cronkhite-Cadana syndrome is a rare non-familial disease. This syndrome is characterized by multiple hamartomatous polyps on the entire gastrointestinal tract except esophagus, nail dystrophy, alopecia and hyperpigmentation. Taste disturbance, abdominal pain, diarrhea and weight loss are common symptoms of it. The pathogenesis and causes of Cronkhite-Canada syndrome remain unknown until now. Although various treatment strategies including steroid therapy have been tried, their prognosis is poor. We report a 68 years old man who were diagnosed Cronkhite-Canada syndrome with esophageal candidiasis. After using combination of steroids and anti-fungal drugs, both Cronkhite-Canada syndrome and esophageal candidiasis were cured.

Osteoclast-like Giant Cell Tumor of the Parotid Gland Accompanied with Carcinoma ex Pleomorphic Adenoma

The origin of osteoclast-like giant cell tumor (OGCT) of the salivary gland has been debated because the prototypic cells of osteoclast-like cells and mononuclear stromal cells are largely unexplained in this gland. Bone marrow-derived CD14+ and CD45+ monocyte-derived multipotential cells (CD14+/CD45+ MOMC) may be one of the possible origins of OGCTs of salivary glands, which have never been explored in salivary OGCTs. We present a case of OGCT accompanied with carcinoma ex pleomorphic adenoma in the parotid gland of a 67-year-old Korean female. The tumor presented as a rapidly growing cervical mass comprising a central area of carcinoma ex pleomorphic adenoma and a peripheral circumferential area of OGCT. The immunohistochemical staining pattern was phenotypically consistent with bone marrow-derived CD14+/CD45+ MOMC. This case is the first report of a salivary OGCT in Korea.

Osteoclast-like Giant Cell Tumor of the Parotid Gland Accompanied with Carcinoma ex Pleomorphic Adenoma

The origin of osteoclast-like giant cell tumor (OGCT) of the salivary gland has been debated because the prototypic cells of osteoclast-like cells and mononuclear stromal cells are largely unexplained in this gland. Bone marrow-derived CD14+ and CD45+ monocyte-derived multipotential cells (CD14+/CD45+ MOMC) may be one of the possible origins of OGCTs of salivary glands, which have never been explored in salivary OGCTs. We present a case of OGCT accompanied with carcinoma ex pleomorphic adenoma in the parotid gland of a 67-year-old Korean female. The tumor presented as a rapidly growing cervical mass comprising a central area of carcinoma ex pleomorphic adenoma and a peripheral circumferential area of OGCT. The immunohistochemical staining pattern was phenotypically consistent with bone marrow-derived CD14+/CD45+ MOMC. This case is the first report of a salivary OGCT in Korea.

A Case of Paraduodenal Pancreatitis and Immunohistochemical Analysis

Paraduodenal pancreatitis (PP) is a rare, distinct form of chronic pancreatitis, and it is related to alcohol abuse in middle-aged men. A 36-year-old man with a history of chronic recurrent pancreatitis for 4 years and alcohol abuse for 15 years presented with abdominal pain. Computed tomography revealed a multilocular cystic mass 3.2 x 3 x 3 cm in size and it was located within the muscular layer of the duodenal wall. The cysts were lined by a single layer of eosinophilic cuboidal epithelial cells that stained positively for mucin (MUC)1, MUC6, cytokeratin (CK)7 and CK19 and they stained negatively for MUC2, MUC5AC and CK5/6. Mild, chronic inflammatory reaction around the cystic wall, Brunner's gland hyperplasia and several clusters of heterotopic pancreatic tissue were noted. We report here on a case of PP and we demonstrated that the pancreatitis was of pancreatic ductal cell origin according to the MUC and CK expression patterns we observed on the immunohistochemical analysis.

The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance

BACKGROUND: E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors. METHODS: Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate. RESULTS: 1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008). CONCLUSIONS: E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.

Microsatellite Instability and p53 Gene Loss of Heterozygosity in Hepatocellular Carcinoma

PURPOSE: Hepatocellular carcinoma (HCC) shows various molecular and genetic alterations in its development and progression. Recently, microsatellite instability (MSI) and the loss of heterozygosity (LOH), have been postulated as useful prognostic factors in many malignant tumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSI has been found to be the result of a mismatched DNA pairing. Our objectives were to evaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors. METHODS: MSI analysis was performed by using polymerase chain reaction with 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the 1998 NCI International Workshop) on 50 surgically resected tumors. p53 LOH was detected with 4 markers (D17S796, TP53, D17S5, D17S513). RESULTS: MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCs exhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53 markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequently detected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, p53 LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with higher tumor grade and invasiveness. LOH-High group showed a significant correlation with advanced HCCs and lymphovascular invasion. There was no demonstrated correlation between MSI and p53 LOH was not demonstrated. CONCLUSION: These results suggest that MSI may be involved to some extent in hepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a useful clinical indicator in determining the prognosis among patients with HCC.

Microsatellite Instability in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: Breast cancer shows various molecular and genetic alterations in its development and progression. Microsatellite alterations, and especially microsatellite instability (MSI) and loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and as a useful prognostic factor for several gastrointestinal malignancies. LOH is related to the allelic loss of various tumor suppressor genes; however, MSI has been found to be the result of an erroneous DNA mismatch repair system and this has been known to be involved in the carcinogenesis of the hereditary non-polyposis colon cancers and some portion of the sporadic colorectal or gastric cancers. Yet MSI has rarely been studied in invasive ductal carcinoma. Our objectives were to evaluate the MSI and p53 protein expression in invasive ductal carcinomas and to correlate this with various clinicopathological factors. METHODS: The MSI analysis was performed by using polymerase chain reaction with five polymorphic microsatellite markers (the BAT25, BAT26, D2S123, D5S346 and D17S250 loci as recommended by the 1998 NCI International Workshop on Microsatellite Instabilitis and RER phenotypes) in 50 surgically resected tumors and each of their non-tumorous counterpart. The p53 protein expression was studied using immunohistochemistry. RESULTS: MSI and a p53 protein expression were detected in 22% and 54% of the tumors and non-tumorous tissues, respectively. MSI was more frequently detected in tumor grade I, T-stage I, non-metastatic tumor and tumor stage I. Also there were rare cases showing a high grade and stage with metastasis in the MSI-high group, in which more than 3 microsatellite loci had MSI. The p53 expression results correlated well with a higher tumor grade. Correlation between MSI and the p53 expression was not found. CONCLUSION: These results may suggest that MSI may be involved in some portions in mammary carcinogenesis and tumor invasion. Also the clinical use of the MSI status may help to determine a better prognosis among invasive ductal cancer patients.

Role of Hepatocyte Growth Factor and c-met Gene Expression in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The hepatocyte growth factor (HGF)/c-Met signal pathway may play various roles in carcinogenesis of several organs. However, studies about this pathway in head and neck cancers, especially oral cavity and oropharyngeal squamous cell carcinoma (SCC), are very rare. Our objectives are to evaluate the relationship between the mRNA and protein expression of HGF and c-met genes in oral cavity and oropharyngeal carcinomas. SUBJECTS AND METHOD: In this study, we examined the mRNA expression of HGF and c-Met by means of the immunohistochemistry (IHC) method and reverse transcription polymerase chain reaction (RT-PCR) in 40 cases of surgically resected oral cavity and oropharyngeal SCC and 10 cases of low grade dysplasia. RESULTS: Using RT-PCR, HGF mRNA amplification was detected in 67.5% and 10% of carcinoma and dysplasia. c-Met mRNA over-expression was detected in 57.5% and 20% of carcinoma and dysplasia. Using IHC, HGF and c-Met protein over-expression was detected in 55% and 62.5% in carcinoma, but not detected in dysplasia. CONCLUSION: These results suggest that HGF/c-Met signal pathway may be associated with the development of oral cavity and oropharyngeal SCC.

Effects of irradiated frozen allogenic bone on bone formation in human fetal osteoblasts / 대한치주과학회지

The purpose of this study was to investigate the effects of irradiated frozen allogenic bone(IFAB) on the cell proliferation and differentiation of human fetal osteoblasts. Human fetal osteoblasts(hFOB1) were cultured to examine the cellular proliferation for 3 days and 5 days with 1mg/ml, 100microgram/ml, 10microgram/ml, 1microgram/ml, 100ng/ml, 10ng/ml, 1ng/ml of IFAB, and to compare the ALP synthesis to control groups for 3 days with DMEM/F-12 1:1 Mixture and 1mg/ml, 100microgram/ml, 10microgram/ml, 1microgram/ml, 100ng/ml, 10ng/ml, 1ng/ml of IFAB. To compare the calcium accumulation, hFOB1 cultured for 23 days were quantified and photographed. The cellular proliferation of hFOB1s treated with IFAB was increased at 5 days to control(p<0.05). The activity of ALP in hFOB1s treated with 100ng/ml IFAB was significantly increased at 5 days(p<0.05). A quantified calcium accumulation in hFOB1 was significantly increased at 100ng/ml, 10ng/ml of IFAB(p<0.05). In the present study, we found that IFAB play a important role of bone formation in the early stage. There was considered that IFAB could be used in the bone graft material.

Clinical Significance of the Expression of Galectin-3 in Thyroid Tumor / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Galectin-3 is a beta-galactoside binding protein, of which the major function is not fully elucidated in malignant tumor. However, galectin-3 is expressed in epithelial cells and contributes to the progression of cancer. Although galectin-3 is expressed in a variety of tissues and plays important roles in malignant transformation or tumor progression, the study on its expression related to clinicopathological parameters in thyroid tumor is rare. So, the present study aims to find out the clinical significance of galectin-3 in thyroid tumor. SUBJECTS AND METHOD: We assessed mRNA and protein expressions of the galectin-3 gene by means of the RT-PCR method and immunohistochemical staining in 100 cases of thyroid tumors (50 papillary carcinomas, 10 follicular carcinomas, 20 follicular adenomas, 20 nodular hyperplasia). The expression of galectin-3 is compared with the clinical prognostic factors of thyroid papillary cancer. RESULTS: Using RT-PCR, galectin-3 mRNA was detected in 41 (82%) in papillary carcinoma, 6 (60%) in follicular carcinoma, 8 (40%) in follicular adenoma and 9 (45%) in nodular hyperplasia cases. Using immunohistochemical staining, galectin-3 protein expressions were detected in 46 (92%), 7 (70%), 3 (15%) and 1 (5%). The expressions of the galectin-3 mRNA and protein were significantly recognized in thyroid papillary carcinoma. However, the galectin-3 mRNA and protein over-expression is not significantly correlated with the clinical prognostic factors of thyroid papillary carcinoma. CONCLUSION: These results suggest that galectin-3 expression may be associated with thyroid papillary carcinoma development.

Effects of Irradiated Frozen Allogenic Bone and Musculoskeletal Transplant Foundation on Bone Formation in Human Fetal Osteoblasts / 대한치주과학회지

The purpose of this study was to investigate the effects of ICB(Irradiated frozen allogenic bone, Rocky Mountain Tissue Bank, USA) and MTF(Decalcified freeze-dried bone allograft, Musculoskeletal Transplant Foundation, USA) on the cell proliferation and differentiation of human fetal osteoblasts. Human fetal osteoblasts (hFOB1) were cultured with 10 ng/ml of ICB and MTF. The negatvie control group was cultured with DMSO and positive control group was cultured with BMP (2 ng/ml). MTT was performed to examine the viability of the cell, and alkaline phosphatase activity was analyzed to examine the mineralization. Calcium accumulation was also evaluated. ICB and MTF did not increase the rate of the cellular proliferation of hFOB1s while they enhanced ALP and calcium accumulation. The expression of osteocalcin (OC) and bone silaloprotein (BSP) increased in hFOB1 treated with ICB and MTF (10 ng/ml). These results suggest that ICB and MTF stimulate osteoblastic activity of the hFOB1.

Expression of Maspin is associated with the Intestinal Type of Gastric Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Maspin is known as a tumor suppressor gene, but its significance has been questioned in various human cancers. The aim of this study was to investigate the expression pattern of Maspin in human gastric adenocarcinomas and its possible correlation with clinicopathological findings. MATERIALS AND METHODS: The expression of Maspin mRNA was measured by nested RT-PCR using 60 frozen adenocarcinomas of the stomach and 31 noncancerous tissues from the proximal resection margin. Immunohistochemical study for Maspin protein expression was carried out using 62 paraffin-embedded tissues, composed of both cancer and noncancerous tissues. RESULTS: Maspin mRNA expression was detected in 80.0% (48 of 60) of the gastric adenocarcinomas, but in only 22.6% (7 of 31) of the normal gastric mucosa (p<0.001). The positive rate of Maspin protein expression was higher in the adenocarcinomas than the normal tissues (62.9% vs. 27.4%, p<0.05). In addition, the intestinal type of tumors showed significantly higher expression levels compared to the diffuse type of tumors (81.5% vs. 48.6%, p<0.05). CONCLUSION: Our results suggest that Maspin is frequently expressed in human gastric cancers, and its expression might be associated with tumorigenesis of the intestinal type of gastric cancer.

Expression of the Matrix Metalloproteinase-2/9 and Tissue Inhibitor of Metalloproteinase-2 Proteins with Heterozygosity of p53 Gene in Thyroid Tumors / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mutations or overexpression of the p53 gene is believed to play an important role in the progression of various human malignant tumors. The type IV collagenase (matrix metalloproteinase: MMP) initiates the degradation of the extracellular matrix and consequently may play a role in the process of tumor invasion and metastasis. Although MMPs are known to be expressed in a variety of tissues and molecular studies in malignant tumor have shown the high frequency of loss of heterozygosity (LOH) in some specific regions, the study on the MMPs expression along with LOH on p53 gene related to clinicopathological parameters in thyroid tumors is very rare. MATERIALS AND METHOD: In this study, we examined the MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP) -2 expression in association with p53 gene LOH using immunohistochemical method and molecular polymorphic analysis in 100 cases of thyroid tumors (50 papillary carcinomas, 10 follicular carcinomas, 20 follicular adenomas, 20 nodular hyperplasias). LOH was examined at four p53 gene related microsatellite loci including TP53, D17S796, D17S5, D17S513. RESULTS: By immunohistochemistry, MMP-2 expression was detected in 37 (74%) papillary carcinomas, 4 (40%) follicular carcinomas, 5 (25%) follicular adenomas and 2 (10%) nodular hyperplasia cases. MMP-9 expression was detected in 35 (70%) papillary carcinomas, 4 (40%) follicular carcinomas, 4 (20%) follicular adenomas and 2 (10%) nodular hyperplasia cases. TIMP-2 expression was detected in 32 (64%) papillary carcinomas, 4 (40%) follicular carcinomas, 4 (20%) follicular adenomas and 1 (5%) nodular hyperplasia cases. By PCR-polymorphism study, p53 LOH was detected in 31 (62%) papillary carcinomas, 8 (80%) follicular carcinomas, 6 (30%) follicular adenomas and 0 (0%) nodular hyperplasia cases. The differences in MMP-2, MMP-9 and TIMP-2 expression rates and p53 LOH between malignant and benign tumors were statistically significant. Also, MMP-2, MMP-9, TIMP-2 expression and p53 LOH correlated well with higher tumor histologic grade. Also statistically significant correlation was found between p53 LOH and lymph node metastasis. The MMP-2 expression showed increased tendency of lymphatic emboli formation and lymph node metastasis, but there was not statistically significant. MMP-2 expression was well correlated with MMP-9 expression and p53 LOH, but there is no remarkable correlation of expression of MMP-2 and MMP-9 comparable to TIMP-2 expression. CONCLUSION: We concluded that the expression of MMP-2, MMP-9 and TIMP-2 with p53 LOH may contribute to the malignant transformation and poorly differentiated grade in thyroid tumors. Also, MMP-2 expression may be regulated by p53 gene.

Multilocular Cyst of Kidney with Malignant Recurrence / 대한비뇨기과학회지

A multilocular cyst of kidney is a rare pathological entity, which has been reported in the literature under several names. These various names reflect the controversy surrounding their nature. This tumor is traditionally regarded as benign in nature and a nephrectomy has to be performed because of the difficulty in its accurate diagnosis. Malignant recurrence of a multilocular cyst of kidney has an even rarer incidence, with only a few cases having been reported. We report a case of 50-year-old male, with an incidentally detected right renal cystic mass. This mass was pathologically confirmed as a multilocular cyst of kidney after a radical nephrectomy, which locally recurred as a malignant mesoblastic nephroma.

Loss of Heterozygosity of E-Cadherin Gene and Protein Expression in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: The E-cadherin gene, located on chromosome 16q22, may play principal roles in cell adhesion with the loss of E-cadherin expression leading to a propensity for a great number of malignant properties. The loss of heterozygosity (LOH) on 16q22 has rarely been studied in invasive ductal carcinomas. Our objectives were to evaluate the LOH of E-cadherin and the protein expression in invasive ductal carcinomas and their correlation with various clinicopathological factors. METHODS: The LOH analysis was performed using polymerase chain reactions with three polymorphic microsatellite markers (D16S419, D16S3106 and D16S498) in 50 surgically resected tumors and their non-tumorous counterparts. The E-cadherin protein expression was studied using immunohistochemistry. RESULTS: The LOH and loss of protein expression were detected in 54% and 46% of the tumors, respectively. There was no LOH or protein loss detected in the non-tumor lesions. The LOH results were well correlated with the tumor size and lymph node metastasis. The protein loss results were well correlated with tumor histological grade. No correlation was found between LOH and protein loss. CONCLUSION: These results suggest that the LOH of E-cadherin may be associated with tumor metastasis and tumor progression and E-cadherin protein loss may be related with the dedifferentiation in some portions of invasive ductal carcinomas. We propose the LOH of E-cadherin and protein loss may contribute to tumor progression by independent mechanism.

DNA Hypermethylation and the Loss of Heterozygosity of Chromosome 16q22 in Hepatocellular Carcinoma

PURPOSE: E-cadherin gene, located on chromosome 16q22, may play crucial roles in the cell adhesion and propensity for more malignant properties of various organs. Although loss of heterozygosity (LOH) and DNA hypermethylation at various chromosomal loci have been reported on many malignant tumors, they have been rarely studied in hepatocarcinogenesis, especially for the E-cadherin gene. Our objectives were to evaluate E-cadherin LOH and hypermethylation in hepatocellular carcinomas (HCC) and to correlate with various clinicopathological facors. METHODS: The LOH analysis was performed by using polymerase chain reaction (PCR) with three polymorphic microsatellite markers (D16S419, D16S3106, D16S498) in 40 surgically resected HCCs and each non-tumorous counterpart. The hypermethylation was studied using methylation specific PCR. RESULTS: LOH and hypermethylation were detected in 35% and 55% of HCC, respectively. Also, LOH and hypermethylation were detected in 0% and 32.5% of non-tumor lesions, respectively. LOH results correlated well with higher tumor histologic grade, tumor size and intrahepatic metastasis or vascular tumor invasion. Hypermethylation results correlated well with presence of cirrhosis. Correlation between LOH and hypermethylation was not recognized, but 45.5% of hypermethylation cases showed LOH detection. CONCLUSION: These results suggest that E-cadherin LOH may be associated with more malignant phenotype and tumor progression. And E-cadherin DNA hypermethylation may participates in the early hepatocarcinogenesis by preceding LOH but not causing LOH.

Expression of the c-met Gene in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: The c-met protein, known as the hepatocyte growth factor (HGF) receptor, is a transmembrane 190 kDa heterodimer having tyrosine kinase activity, and it is encoded by the c-met oncogene. The HGF/c-met signaling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities. Although HGF and c-met are known to be expressed in a variety of organs and they play important roles in signal transduction, studies on its expression and its correlation to the clinicopathological parameters of breast cancer are very rare. METHODS: In this study, we examined the c-met mRNA and the c-met protein expression by utilizing RT-PCR and immunohistochemical methods for 50 cases of invasive ductal carcinomas (IDCs) and 20 cases of normal breast tissues. RESULTS: The c-met mRNA amplification was detected in 35 cases of IDCs (70%), but not in the normal tissues. The c-met protein overexpression was detected in 27 cases of IDCs (54%) and 2 cases of normal breast tissue (10%). Both the mRNA amplification and protein overexpression rates were significantly higher in tumor than in the normal breast tissue. The c-met mRNA amplification showed a tendency to increase in an invasive cancer and nodal metastasis. The c-met protein overexpression was significantly correlated with the well differentiated grade of tumor and it showed a tendency to decrease in the metastatic tumors. The concordance between both the mRNA amplification and protein expressions were not observed. CONCLUSION: These results suggest that the HGF/c-met signal pathway may be associated with the development of breast cancer. c-met mRNA amplification may play important roles both in tumor progression and metastasis. c-met protein overexpression may contribute to the morphogenesis of well-differentiated tumor.