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Woo Ho Kim

Publications and source records attributed to Woo Ho Kim.

63 records · Page 4Linked to original sources

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary.

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.

Adenocarcinoma↗

Mutation and altered expression of beta-catenin during gallbladder carcinogenesis.

Gallbladder carcinoma has two main morphologic developmental pathways: a dysplasia-carcinoma sequence and an adenoma-carcinoma sequence. beta-Catenin is a key regulator of the cadherin-mediated cell adhesion system, and altered expression and mutation of beta-catenin have been identified in many human malignancies. To clarify its role in gallbladder carcinogenesis, we investigated mutation and immunohistochemical expression of beta-catenin in adenomas, dysplasias, and carcinomas. We classified adenomas according to the expression of apomucins and cytokeratin and compared the mutational and expression pattern among each type. beta-Catenin mutations were identified in 58% (14 of 24) of the adenomas, and they were absent from all carcinomas (37 cases) and dysplasias (13 cases). Altered expression of beta-catenin, such as nuclear or cytoplasmic expression and loss of membranous expression, was also significantly higher in adenomas than in dysplasias or carcinomas (p <0.001). Of the adenomas, papillary adenomas and tubular adenomas of intestinal type showed infrequent beta-catenin abnormality, which was similar to the carcinomas. The cytoplasmic and nuclear expression of beta-catenin in carcinomas was correlated with less aggressive tumor behavior; in particular, cytoplasmic expression was associated with improved patient outcome (p = 0.028). Gallbladder adenoma may be a heterogeneous entity, and the majority of adenomas are not responsible for carcinoma progression.

Adenocarcinoma↗

Manganese superoxide dismutase expression correlates with a poor prognosis in gastric cancer.

OBJECTIVE: The biologic significance of superoxide dismutase (SOD) in transformed gastric carcinoma cells is unclear. The aim of this study was to examine the role of SOD as a prognostic indicator of gastric carcinomas and its association with other clinicopathological factors. METHODS: Expression of MnSOD and Cu/ZnSOD was evaluated immunohistochemically in gastric carcinomas and adenomas using tissue-array methods. The correlation between SOD immunoreactivity and clinical outcome or clinicopathological factors was investigated. RESULTS: MnSOD expression was associated with a poor patient prognosis and was strong in advanced gastric cancer, in the well-differentiated type and in the presence of lymphoid stroma (p < 0.05). On the other hand, there was no association between Cu/ZnSOD expression and patient survival. Cu/ZnSOD immunoreactivity was strong in advanced gastric cancer and in the presence of lymphoid stroma (p < 0.05) and was weak in signet ring cell type. CONCLUSION: MnSOD immunoreactivity is significantly associated with poor outcome in gastric carcinoma patients although both MnSOD and Cu/ZnSOD have a connection with several clinicopathological parameters with some overlap.

Adenocarcinoma↗

Expression of beta-catenin and E-cadherin in the adenoma-carcinoma sequence of the stomach.

beta-catenin plays an important role in the Wnt signaling pathway and the E-cadherin-catenin complex plays a critical role in the maintenance of normal tissue architecture. An alteration of any of the components of the E-cadherin-catenin complex is believed to result in the loss of cell-cell adhesion and to contribute to carcinogenesis. In order to evaluate such alterations in the gastric adenoma-carcinoma sequence, the abnormal expression of beta-catenin and E-cadherin and the mutations of beta-catenin exon 3 were studied. In the case of beta-catenin, nuclear immunoreactivity was noted in 17 (11.3%) out of 150 adenomas and 19 (17.1%) out of 111 carcinomas (p = 0.18). Among 51 gastric adenomas, no mutations were detected by direct sequencing analysis. The loss of membranous expression of both beta-catenin and E-cadherin linearly increased with tumor progression, however, beta-catenin loss was more frequent than E-cadherin. Our results show that the nuclear expression and membranous loss of beta-catenin without exon 3 mutation is relatively frequent in gastric adenomas. These suggest that alteration of other genes is primarily responsible for the nuclear translocation of beta-catenin in gastric adenomas.

Adenoma↗

Loss of heterozygosity in ampulla of Vater neoplasms during adenoma-carcinoma sequence.

BACKGROUND: Ampulla of Vater cancers arise from precancerous lesions and existence of an adenoma-carcinoma sequence is based on morphological observations. MATERIALS AND METHODS: We studied the loss of heterozygosity (LOH) in 22 adenomas, 32 carcinomas and 10 metastatic lesions using nine dinucleotide-repeated sequences in 3p, 8p, 8q, 9p, 10q, 13q, 17p, 17q, 18q. RESULT: High LOH frequencies (> 50%) of 9p (IFNA) and 17p (TP53) were observed in adenomas and carcinomas. The frequency of LOH is higher in adenoma (55.6%) than in carcinoma (40%) for 8p (D8S261), but it is the same in cases having adenoma (57.1%) and carcinoma (57.1%) in the same lesion. LOH for 13q (D13S118), 17q (D17S520) and for 18q (D18S34) were more common in carcinomas than in adenomas, but statistically a significant difference was observed only on 13q (p < 0.05). Fractional allelic loss (FAL) is not correlated with any of the clinicopathological parameters. CONCLUSION: Tumor suppressor genes located in the 8p, 9p and 17p chromosomes might be associated with the early stage of tumorigenesis and that in 13q is involved during the adenoma-carcinoma progression.

Adenoma↗

Expression of family A melanoma antigen in human gastric carcinoma.

BACKGROUND: Since the members of the MAGE (melanoma antigen) gene family have been reported to be expressed in tumor cells but not in normal tissues, they have been considered as targets for tumor-specific immunotherapy. MATERIALS AND METHODS: The expression pattern of MAGE-A genes and their expression mechanisms were investigated in 10 gastric cancer cell lines and 1,097 gastric carcinoma specimens by RT-PCR, IHC, Western blot and MSP. RESULTS: MAGE-A1, -A2 and -A3 gene transcripts were detected in 1, 3 and 4 of 10 gastric cancer cell lines, respectively. In those cases in which the mRNA expression of MAGE-A2 or -A3 was detected, the promoters of the corresponding genes were hypomethylated. MAGE-A protein expression was detected in 30% (3/10) of the cell lines and 15.8% (173 out of 1,097) of the carcinoma specimens. Promoter hypomethylation of the MAGE-A2 or -A3 genes correlated with their expression in primary gastric cancer tissue and gastric cancer cell lines. MAGE-A protein expression was associated with tumor invasiveness (p=0.002), lymph node metastasis (p<0.001), advanced pathologic stage (p<0.001) and a worse prognosis (p<0.005). CONCLUSION: MAGE-A protein expression occurred due to promoter hypomethylation in a minor subset of gastric cancers, and MAGE-A expression increased during the progression of the gastric cancer.

Antigens, Neoplasm↗

Silencing and CpG island methylation of GSTP1 is rare in ordinary gastric carcinomas but common in Epstein-Barr virus-associated gastric carcinomas.

BACKGROUND: The GSTPI gene encodes for glutathione S-transferase pi (GST-pi), which protects cells from cytotoxic agents. The carcinogenic role of this enzyme is at issue because functional polymorphisms have been shown to be a risk factor of human cancer. Moreover, GST-pi protein loss has frequently been reported in various human cancers. MATERIALS AND METHODS: The expression of GST-pi and the methylation status of the promoter area of GST-pi were investigated in gastric carcinomas. Eleven human SNUgastric cancer cell lines, PC-3 prostate cancer cell lines, various cancer tissues and normal gastric mucosa tissues were analyzed by immunohistochemistry, in situ hybridization, Western blot and methylation specific PCR. RESULTS: Only 22 (2.0%o) out of 1081 cases showed loss of GST-pi expression. Interestingly, 16 out of 22 GST-pi-negative cases were Epstein-Barr virus (EBV)-associated gastric carcinomas. The loss of expression of GST-pi among EBV-associated gastric carcinomas was found to be 27.1% (16/59), but to be 0.6% (6/1022) in EBV-negative gastric carcinomas (p < 0.001). Eight out of 16 cases with loss of GST-pi expression showed CpG island methylation in the GSTP1 promoter region, while none of the normal gastric mucosa or EBV-negative gastric carcinomas showed methylation (p < 0.001). CONCLUSION: These findings demonstrate that the loss of GST-pi expression is clustered in a subset of gastric carcinomas with EBV incorporation, and that the methylation of the promoter of the GSTP1 gene is correlated with this loss of GST-pi expression. Our results suggest that GST-pi abrogation by CpG island hypermethylation may account for EBV-associated gastric carcinoma.

Cell Line, Tumor↗

Expression of E-cadherin and beta-catenin in the adenoma-carcinoma sequence of ampulla of Vater cancer.

BACKGROUND/AIMS: Ampullary carcinoma is uncommon but provides a good model for adenoma-carcinoma sequence. During the adenoma-carcinoma transition, the tumor cells should acquire the ability to invade. The E-cadherin-catenin complex connects the adjacent epithelial cells at the zona adherens, and this adhesion interferes with the tumor cell invasion. METHODOLOGY: 111 cases of ampullary carcinoma were investigated with E-cadherin and beta-catenin expression with immunohistochemistry and the result was compared with their clinicopathologic and survival results. Forty-nine (44.1%) cases were associated with adenomatous component. RESULTS: Expressional loss of E-cadherin was detected in 3 (6.1%) adenomas and 73 (65.8%) carcinomas, and the expressional loss was significantly associated with tumor cell differentiation (p<0.05) and survival (p<0.05) in carcinoma. In beta-catenin immunostaining, 4 (8.2%) adenomas and 45 (40.5%) carcinomas showed abnormal staining patterns either as nuclear staining or as a loss of membrane staining. The cases with membranous loss of beta-catenin expression were correlated with poor survival rate. CONCLUSIONS: Alteration of E-cadherin and beta-catenin is a late event during the adenoma-carcinoma sequence in ampullary neoplasms, and the loss of membranous expression of both E-cadherin and beta-catenin is closely correlated with less differentiated histology and poor prognosis.

Adenoma↗