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Woo Ho Kim

Publications and source records attributed to Woo Ho Kim.

17 recordsLinked to original sources
PubMed2003

Prognostic significance of Bcl-2 and p53 expression in gastric cancer.

BACKGROUND AND AIMS: Apoptosis regulates cell death and influences cell proliferation and therefore may play an important role in development or growth of various malignant tumors. The Bcl-2 and p53 are closely linked in the regulation of apoptosis. We investigated the prognostic significance of Bcl-2 and p53 expression in patients with gastric cancer. PATIENTS AND METHODS: Immunohistochemistry was used to study Bcl-2 and p53 expression in 308 consecutive patients with gastric cancer. RESULTS: Bcl-2 expression was positive in 39 patients (12.7%) and showed a significant negative correlation with depth of invasion and lymph node metastasis. p53 expression was observed in 105 patients (34.1%) and was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and intestinal type. Patients with Bcl-2(+) tumors showed a trend to better 5-year survival rate (81%) than those with Bcl-2(-) negative tumors (71%). The 5-year survival rate in p53 positive cases (60%) was significantly lower than that in p53-negative cases (78%). In addition, p53 expression showed a significantly poorer prognosis in both diffuse and intestinal types. In multivariate analysis restricted to patients with R0 resection p53 expression was an independent prognostic factor (relative risk: 2.063). In combined assessment of p53 and Bcl-2 expression the group with p53(+)/Bcl-2(-) tumors showed significantly worse 5-year survival (57%) than the other groups, while best survival was seen in the group with p53(+)/Bcl-2(+) tumors (100%). CONCLUSION: p53 expression is an unfavorable prognostic factor in gastric cancer. Bcl-2 expression may have possible prognostic value when combined with p53 expression.

Adult↗
PubMed2003

Alteration of O6-methylguanine-DNA methyltransferase in colorectal neoplasms in sporadic and familial adenomatous polyposis patients.

DNA repair failure is known to be a critical event during carcinogenesis of colorectal cancers. To investigate whether O(6)-methylguanine-DNA methyltransferase (MGMT) is altered during colorectal carcinogenesis, we performed immunohistochemical staining on 265 sporadic colorectal cancers, 113 sporadic adenomas, 33 familial adenomatous polyposis (FAP) colorectal cancers, and 93 FAP adenomas. Sixty-seven of 265 sporadic colorectal cancer cases and five of 113 sporadic adenoma cases showed loss of MGMT expression (P < 0.001). Among FAP patients, four of 33 cancers and six of 93 adenomas showed loss of MGMT protein expression. When we compared the association between MGMT promoter hypermethylation and protein expression, almost all cases without a methylated allele were positive for the expression of MGMT. In contrast, cases with promoter methylation frequently showed loss of MGMT expression (P < 0.01). Loss of MGMT was correlated with some clinicopathological characteristics, i.e., tumor invasion (P = 0.013) and stage (P = 0.035) in sporadic colorectal cancer, and degree of atypism (P = 0.042) in sporadic adenoma. Our results show that loss of expression of MGMT occurs more frequently in cancer than in adenoma in both sporadic and FAP patients, and that loss of expression of MGMT is associated with hypermethylation of the promoter area of MGMT gene.

Adenoma↗
PubMed2003

Tumour suppressor gene expression correlates with gastric cancer prognosis.

The loss of tumour suppressor genes (TSGs) is a key event in many human cancers, including gastric carcinoma. Many TSG candidates have been studied, but their roles in gastric carcinogenesis remain unclear. To clarify the clinical significance of TSG expression in gastric carcinoma, the expression of various TSG candidates (p53, E-cadherin, FHIT, smad4, rb, VHL, PTEN, MGMT, p16, and KAI1), as well as other proteins (bcl-2, MUC1, MUC2, MUC5AC, MUC6, CEA, CD44, beta-catenin, C-erbB2, and cyclin B2), was evaluated immunohistochemically in 329 consecutive gastric carcinomas using the tissue array method. The overexpression of p53 and MUC1 (p < 0.01) and the loss of expression of smad4 (p = 0.04), FHIT (p = 0.03), MGMT (p = 0.01), E-cadherin, KAI1, and PTEN (p < 0.01) were found to be significantly associated with poor gastric carcinoma prognosis. Seven out of eight survival-associated proteins were found to be protein products of TSGs. The gastric carcinomas were divided into five groups according to the grade of alteration in TSG expression. No TSG expression loss was found in 32 cases (TSG1). One TSG loss was found in 47 cases (TSG2), two in 67 cases (TSG3), three or four in 64 cases (TSG4), and five, six, or seven in 38 cases (TSG5). The grade of TSG expression was confirmed to be significantly associated with WHO classification (p = 0.04), pTNM stage, lymphatic invasion, and patient survival (p < 0.01 for the latter three). By multivariate analysis, the grade of TSG expression was found to be significantly and independently associated with patient survival (p < 0.01). In conclusion, the findings of this study suggest that the cumulative loss of TSG expression in gastric carcinoma is important in determining patient survival.

Acid Anhydride Hydrolases↗
PubMed2003

Epstein-Barr virus and microsatellite instability in gastric carcinogenesis.

Little information is available concerning the relationship between transforming viruses and microsatellite instability (MSI). We evaluated Epstein-Barr virus (EBV) using in situ hybridization for EBV-encoded small RNAs and MSI using the polymerase chain reaction in surgically resected gastric cancer. The study subjects included 298 consecutive cases of solitary gastric carcinoma, 63 gastric carcinomas in young patients (</=30 years old), 64 cases of gastric cancer coexisting with gastric adenoma in a single lesion, 26 cases of gastric remnant cancer, and 98 carcinomas from 47 patients with synchronous multiple gastric carcinomas. There was no overlapping case among these subsets of gastric cancer. None of these 549 gastric carcinomas demonstrated both EBV positivity and MSI positivity. Furthermore, the EBV-positive and the MSI-positive cases showed a mutually negative association in all subsets of gastric cancer. 5.7% of consecutive solitary gastric carcinomas were EBV positive, and 9.7% were MSI positive. EBV was positive in 1.6% of gastric cancers coexisting with gastric adenoma, 12.7% of younger patients, 28.6% of gastric remnant cancer with previous gastrectomy for benign disease, and 14.5% of synchronous cancers without adenoma. MSI was found in 1.6% of younger patients, 18.8% of gastric cancers coexisting with gastric adenoma, 25% of gastric remnant cancer with previous gastrectomy for gastric cancer, and in 53.3% of synchronous gastric carcinomas having gastric adenoma remote from the cancer. In conclusion, the carcinogenic roles of EBV and MSI may be different in terms of each subset of gastric cancer. EBV and MSI may contribute to functionally equivalent pathways in gastric carcinogenesis.

Adenoma↗
PubMed2003

Expression of mucins and cytokeratins in primary carcinomas of the digestive system.

To determine the most optimal treatment of cancer patients, it is fundamental to classify human carcinomas according to their primary anatomical site of origin. As for some patients, it is difficult to identify cancers occurring at obscure location and overlapping adjacent sites. The aim of this study is to partition the primary site of 486 patients in cancers of the digestive system by the expression pattern of the mucins and cytokeratins typifying each site. The expressions of MUC1, MUC2, MUC5AC, MUC6, CK7, CK8, CK13, CK14, CK18, CK19 and CK20 were evaluated immunohistochemically in 426 adenocarcinomas and 60 hepatocellular carcinomas using the tissue-array method. The finding of MUC series showed their characteristics in case of MUC2 in the appendix cancer and MUC1 and 5AC in pancreas cancer. As for CKs 7, 13, and 19, and 20 had a feature in cancers of common bile duct, liver, and appendix, respectively. We classified cancers in 11 sites by characteristic expression of antibodies. The sensitivity, specificity, positive predictive value, and diagnostic efficacy of significant antibodies were calculated with deducing the dichotomous tree made by SPSS 10.0. Six of 11 antibodies, CK 7, CK13, CK19, CK20, MUC1, and MUC5AC distinguished 6 groups from 11 sites. We also executed the clustering of cancers to investigate total relationship among cancers. They fell into three categories, which corresponded to embryologic origin. Unlike other sites, the small intestine and colorectum cancers expressed significantly different patterns to their sublocations. Mucins and CKs showed expression patterns to classify the primary sites of digestive cancers and may be helpful in predicting the primary sites of digestive cancers.

Adenocarcinoma↗
PubMed2003

Fatty acid-CoA ligase 4 is overexpressed in human hepatocellular carcinoma.

Fatty acid-CoA ligase 4 (FACL4) is a central enzyme controlling the unesterified arachidonic acid (AA) level in cells. It has been shown that FACL4 blocks apoptosis and promotes colon carcinogenesis by lowering the cellular level of unesterified AA. Consistent with this, FACL4 is upregulated in colon adenocarcinoma. The status of FACL4 in other tumors including hepatocellular carcinoma (HCC) is not known. Here, we report that FACL4 is overexpressed in human HCC compared with adjacent normal liver tissues. FACL4 mRNA and protein were overexpressed in 5 out of 12 (41.7%) and 3 out of 8 (37.5%) cases of HCC, respectively. Immunohistochemical staining showed strong fine granular intracytoplasmic staining in tumor cells, whereas we observed occasional weak staining in normal liver tissues surrounding the tumors. We found that 14 out of 37 (37.8%) HCC expressed moderate to strong FACL4 immunostaining. Both normal adult and fetal liver tissues showed very weak to no detectable staining, whereas 3 out of 10 (30%) cirrhotic livers expressed weak staining. In addition, we found that 4 out of 8 (50%) human hepatoma cell lines expressed high levels of FACL4 by northern blot analysis. Our results show that FACL4 is a new molecular marker for HCC and suggest that the FACL4 pathway may be involved in liver carcinogenesis.

Adult↗
PubMed2002

Identification of genes differentially expressed between gastric cancers and normal gastric mucosa with cDNA microarrays.

To identify genes whose alterations lead to gastric cancer, gene expression profiles have been obtained from 22 gastric cancer tissues and their surrounding gastric mucosa tissues. A total of 16 genes were differentially expressed in more than 50% of gastric cancer tissues compared with surrounding gastric mucosa tissues. Genes such as HMG-Y, fibroblast collagenase inhibitor, and osteopontin are among those that are overexpressed in over 50% of the gastric cancer tissues. Dihydrodiol dehydrogenase, ribonuclease A, and glutathione peroxidase are among those genes that are underexpressed in over 50% of the gastric cancer tissues. We identified genes that are associated with clinical phenotypes of patients with gastric cancers. Alpha-II spectrin, Na/K-ATPase and KIAA0111 are those that are enhanced in intestinal type of gastric cancer. Gene such as platelet-endothelial tetraspan antigen 3 was enhanced in highly metastatic gastric cancer tissues.

Base Sequence↗
PubMed2002

Identification and characterization of a novel cancer/testis antigen gene CAGE.

We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. The corresponding gene was named cancer-associated gene (CAGE). PCR of human x hamster Radiation Hybrids showed localization of CAGE on the human chromosome Xp22. Transient transfection of CAGE showed predominantly nuclear localization. Both Western blot and plaque assay indicated seroreactivity of CAGE protein. We found that demethylation played a role in the activation of CAGE in some cancer cell lines that do not express it. Cell synchronization experiments showed that the expression of CAGE was related with cell cycle. This suggests that CAGE might play a role in cellular proliferation. Because CAGE is expressed in a variety of cancers but not in normal tissues except testis, this gene can be a target of antitumor immunotherapy.

Adenoma↗
PubMed2002

Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma.

Aberrant methylation of promoter CpG islands of human genes has been known as an alternative mechanism of gene inactivation and contributes to the carcinogenesis in many human tumors. We attempted to determine the methylation status of 18 genes, or loci known to be frequently methylated in cancers of other organs, in 79 resected intrahepatic cholangiocarcinomas and 15 normal bile duct epithelium by methylation-specific polymerase chain reaction and correlated the data with clinicopathological findings. Methylation frequencies of the loci tested in intrahepatic cholangiocarcinomas were 59.5% for 14-3-3sigma,26.6% for APC, 21.5% for E-cadherin, 17.7% for p16, 11.4% for MGMT, 11.4% for THBS1, 8.9% for p14, 8.9% for TIMP3, 7.6% for DAP-kinase,6.3% for GSTP1, 5.1% for COX-2, 50.6% for MINT12, 40.5% for MINT1, 15.4% for MINT25, 35.4% for MINT32, and 1.3% for MINT31. Sixty-two (78.5%) of the 79 intrahepatic cholangiocarcinomas had methylation in at least one of these loci. Methylation was not detected in normal bile duct samples. There was a significant correlation between methylation and expressional decrease or loss of p16, E-cadherin, and GSTP1 proteins (P = 0.028, P = 0.044, and P < 0.001, respectively). The overall survival was poorer in the patients with CpG island methylation of APC, p16, and TIMP3 than in the patients without methylation (Kaplan-Meier log-rank test, P = 0.0128, 0.0447, and 0.0137, respectively). Age, gender, tumor stage, gross type, histological type, and differentiation had no correlation with methylation status of the specific gene. These results suggest that methylation is a frequent event in cholangiocarcinomas and contributes to the cholangiocarcinogenesis, and that CpG island methylation of APC, p16, or TIMP-3 may serve as a potential prognostic biomarker of the cholangiocarcinomas.

Adenomatous Polyposis Coli Protein↗
PubMed2002

Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma.

CpG island methylation is an important mechanism for inactivating the genes involved in tumorigenesis. Gastric carcinoma (GC) is one of the tumors that exhibits a high frequency of aberrant CpG island methylation. There have been many reports suggesting a close link between Epstein-Barr virus (EBV) and the development of GC. However, little is known about the oncogenic mechanism of EBV in gastric carcinogenesis. Twenty-one cases of EBV-positive GC and 56 cases of EBV-negative GC were examined for aberrant DNA methylation of the CpG islands of 19 genes or loci and the differences in the methylation frequency between EBV-positive and -negative GCs were investigated to determine a role of aberrant methylation in EBV-related gastric carcinogenesis. The average number of methylated genes or loci was higher in EBV-positive GCs than in EBV-negative GCs (13.4 versus 7.8, respectively, P < 0.001). EBV-positive GCs showed methylation in at least 10 CpG islands (52.6% of the tested genes), whereas 62.5% of EBV-negative GCs showed methylation in <10 CpG islands. THBS1, APC, p16, 14-3-3 sigma, MINT1, and MINT25 were methylated at a frequency >90% in EBV-positive GCs. The methylation frequency difference in the respective CpG islands between EBV-positive and -negative GCs was statistically significant (P < 0.05). Among these genes or loci, the methylation frequency of p16 in the EBV-positive GCs was more than three times higher than in the EBV-negative GCs. The PTEN, RASSF1A, GSTP1, MGMT, and MINT2 were methylated in EBV-positive GCs at a frequency of more than three times that of the EBV-negative GCs. These results demonstrate a relationship between EBV and aberrant methylation in GC and suggest that aberrant methylation may be an important mechanism of EBV-related gastric carcinogenesis.

CpG Islands↗
PubMed2002

Promoter methylation and silencing of PTEN in gastric carcinoma.

The PTEN/MMAC1/TEP1 gene (phosphatase and tensin homolog deleted on chromosome 10/mutated in multiple advanced cancers/TGF-beta regulated and epithelial cell enriched phosphatase 1), which regulates the signaling pathways of Akt, is a novel tumor suppressor gene implicated in multiple cancers. Because a number of tumor suppressor genes are known to be silenced by aberrant promoter methylation, we examined the methylation status of the 5' CpG islands of PTEN using methylation-specific PCR. The altered expression of PTEN in 310 gastric carcinomas was analyzed by immunohistochemical staining using tissue-array and clinicopathologic profiles related to PTEN expression were characterized. Of 310 consecutive gastric carcinomas, 62 cases (20%) showed expression loss of PTEN. Altered PTEN expression was significantly associated with tumor depth and size, lymphatic invasion, advanced stage, pTNM stage, and patient survival (p < 0.001). The promoter methylation frequency of PTEN was found to be present in 26 (39%) of 66 cases examined, and 19 (73%) of 26 gastric cancer tissues showing promoter methylation exhibited the loss of PTEN expression. Abnormalities in the expression of PTEN significantly correlated with promoter methylation (p < 0.001). In conclusion, silencing of the PTEN gene occurs frequently in gastric carcinoma and aberrant promoter methylation is a major mechanism of silencing of the PTEN gene. The abnormalities of the PTEN gene are associated with tumor progression, metastasis, and survival.

Adenocarcinoma, Mucinous↗
PubMed2002

Distinct clinical features and outcomes of gastric cancers with microsatellite instability.

Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <.05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <.001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-beta type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =.046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Epstein-Barr virus, p53 protein, and microsatellite instability in the adenoma-carcinoma sequence of the stomach.

To elucidate the adenoma-carcinoma sequence in the stomach, we investigated Epstein-Barr virus (EBV) incorporation, p53 overexpression, and microsatellite instability (MSI) in gastric adenomas and carcinomas. The study involved 66 cases of gastric carcinomas within or adjacent to adenomas (adenoma-carcinoma cases), 81 cases of simple adenomas (without carcinoma), and 306 de novo carcinomas (without adenoma focus). EBV incorporation was revealed in 1 (1.5%) of the adenoma-carcinomas, in none of the adenomas, and in 17 (5.6%) of the de novo carcinomas. p53 overexpression was observed in 24.2% (16 of 66) of the adenomas in the adenoma-carcinoma cases and in 36.5% (23 of 63) of corresponding carcinomas (kappa = 0.63, P = 0.00). MSI was positive in 12.3% (8 of 65) of the adenomas in the adenoma-carcinoma cases and in 18.8% (12 of 64) of the corresponding carcinomas (kappa = 0.77, P = 0.00). In conclusion, EBV incorporation is not possibly associated with the gastric adenoma-carcinoma sequence, whereas the gastric adenoma-carcinoma sequence seems to be supported in terms of p53 overexpression or MSI. The transcriptional activation of EBV may occur relatively late (after the adenoma stage) in the gastric adenoma-carcinoma sequence.

Adenoma↗
PubMed2002

Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma.

Aberrations of G1-S cell cycle arrest and TGF-beta/Smad pathway are critical events in human carcinogenesis. We studied alterations of both pathways by immunohistochemical staining for p53, p16, p27, cyclin D1, Rb and Smad4/Dpc4 in 42 intrahepatic cholangiocarcinomas (ICCs). Abnormal nuclear overexpression of p53 and cyclin D1 was noted in 15 (35.7%) and 26 (61.9%) cases, respectively. Total loss of p16, p27, Rb and Smad4 was detected in 15 (35.7%), 13 (31.0%), 5 (11.9%) and 19 (45.2%) cases, respectively. Forty cases (95.2%) showed aberrations of at least one of the pathways, of which 21 (50%) revealed abnormality in G1-S pathway only, 17 (40.5%) had abnormalities in both pathways and 2 (4.8%) had an abnormality in TGF-beta/Smad pathway only. Among the examined genes, loss of Smad4 was found to have a positive relationship with the pTNM stage (P < 0.05). The overall stage of the high-altered group (alterations in 2 to 5 of the genes, n = 29) was significantly higher than that of the low-altered group (alteration of one or no gene, n = 13) (P < 0.01). We also examined the expression of above genes in the accompanying biliary dysplasia and found out abnormal expression of p53, cyclin D1 or p16 in 7 out of 13 dysplastic lesions. Our data suggest that abnormal G1-S cell cycle and altered TGF-beta/Smad pathway are major events in cholangiocarcinogenesis. Moreover, there might be a possible cumulative effect of the alterations in the examined genes upon the clinical outcome of patients with resectable ICCs.

Adult↗
PubMed2002

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↗
PubMed2002

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↗