Biomedical subjects

W H Kim

Publications and source records attributed to W H Kim.

At least 19 recordsLinked to original sources

PubMed2002

Inactivation of O6-methylguanine-DNA methyltransferase by promoter CpG island hypermethylation in gastric cancers.

Promoter hypermethylation of CpG islands in tumour suppressor genes can lead to transcriptional inactivation. To investigate the association between methylation and expression at O6-methylguanine-DNA methyltransferase, we performed methylation-specific PCR and immunohistochemistry in 149 gastric carcinomas. Promoter methylation was found in 14.1% of tumours and loss of expression was detected in 11.4% of tumours. To examine correlation between the O6-methylguanine-DNA methyltransferase expression and the clinical data, we investigated O6-methylguanine-DNA methyltransferase expression in 315 consecutive gastric carcinomas. A similar frequency of loss of O6-methylguanine-DNA methyltransferase expression was confirmed in these cases. The loss of O6-methylguanine-DNA methyltransferase expression was significantly associated with pTNM stage (P=0.037), tumour invasion (P=0.02), microsatellite instability (P=0.041) and overall survival (P=0.01). Among 11 gastric cancer cell lines, SNU-620 showed the loss of O6-methylguanine-DNA methyltransferase expression as well as promoter methylation. After treatment with 5-aza-2-deoxycytidine, a demethylating agent, SNU-620 re-expressed O6-methylguanine-DNA methyltransferase mRNA. In summary, we suggest that during gastric carcinogenesis, the loss of O6-methylguanine-DNA methyltransferase expression frequently occurs via the hypermethylation of the CpG islands of the promoter region, and that this is significantly associated with the clinicopathological characteristics.

Antimetabolites, Antineoplastic↗

PubMed2002

Comprehensive analysis of promoter methylation and altered expression of hMLH1 in gastric cancer cell lines with microsatellite instability.

PURPOSE: Aberrant methylation of the promoter CpG island of hMLH1 is associated with gene silencing in colon cancer and gastric cancer with microsatellite instabilities (MSI). We analyzed the pattern of promoter methylation causing gene silencing. METHODS: Comprehensive analysis of hMLH1 promoter was performed by bisulfite genomic sequencing in human gastric cancer cell lines. Altered expression of hMLH1 was examined by the immunocytochemical staining method and RT-PCR, and microsatellite instability was examined using two representative mononucleotide repeat microsatellite markers, BAT-25 and BAT-26. RESULTS: As a result, MSI-positive gastric cancer cell lines were methylated extensively at the overall promoter region. MSI-negative gastric cancer cell lines - except in SNU-620 - were unmethylated completely at the overall promoter region including the more upstream region in contrast to colorectal cancer cell lines. Even though SNU-620 was methylated fully at the overall promoter region - except for partial methylation at the specific region (from -270 to -199) near the transcriptional start - hMLH1 protein was expressed. CONCLUSION: Our data suggest that the methylation density of a specific region plays an important role in gene inactivation of hMLH1 and that the methylation status of the more upstream promoter region and exon 1 start region are not essential for gene inactivation.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Tracheal compression by elongated aortic arch in patients with congenitally corrected transposition of the great arteries.

We investigate the tracheal compression by aortic arch in patients with congenitally corrected transposition of the great arteries. Fourteen patients whose ascending aorta was connected to descending aorta on the contralateral side were divided into two groups according to the severity of tracheal compression on lateral angiogram: group 1 (stenosis > or = 50%, eight patients) and group 2 (stenosis < 50%, six patients). We compared the following variables between the groups: aortic size, lateral displacement of ascending aorta, retrosternal space, and contour of aortic arch. Spiral computed tomography (CT) was done in five patients of group 1. The ratio between measured and normal diameters of ascending aorta of group 1 was significantly larger than that of group 2 (1.57 +/- 0.14 compared to 1.19 +/- 0.26, p = 0.014). There was linear correlation between the tracheal compression and aortic size (r = 0.69, p = 0.001). The ascending aorta was positioned more laterally and the aortic arch was located more posteriorly in group 1. In four patients with decreased tracheal compression after surgery, aortic size decreased and the ascending aorta restored its anterior position. Spiral CT showed transversely oriented aortic arch and severe tracheal compression in the anteroposterior direction by aortic arch. The tracheal compression by aortic arch in corrected transposition is common when the descending aorta is located on the contralateral side of the ascending aorta. Aortic size, posterior position, elongation, and end-on appearance of the aortic arch are the useful predictors of tracheal compression.

Adolescent↗

PubMed2001

Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein X (HBX) or HCV core protein: involvement of TNF-alpha receptor 1-independent and -dependent mechanisms.

Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.

Acetaldehyde↗

PubMed2001

MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators.

BACKGROUND: Although mucin expressions appear to be correlated with prognoses in patients with various cancers, several studies have reported conflicting and inconclusive results on the prognostic significance of mucin expression in gastric carcinomas. METHODS: To clarify the correlations between clinicopathologic profiles and the patients' survival, the expression of MUC1, MUC2, MUC5AC, MUC6 mucins and the p53 protein were evaluated immunohistochemically in 300 consecutive gastric carcinomas using the tissue-array method. In addition, 59 gastric adenomas and 57 adenoma-associated carcinomas were investigated. RESULTS: MUC1 was expressed in 2 (3.4%) cases of gastric adenoma, and MUC2 in 19 (32.2%) cases of gastric adenoma, out of a total of 59 lesions. In consecutive gastric carcinomas, 24.3% of gastric carcinomas expressed MUC1, 27.3% expressed MUC2, 38.0% expressed MUC5AC and 12.7% expressed MUC6. The rate of MUC1 expression in gastric carcinomas was significantly higher than in associated gastric adenomas (P < 0.01). The patients with MUC1-positive carcinomas showed significantly poorer survival than those with MUC1-negative carcinomas. On the other hand, MUC2, MUC5AC and MUC6 expressions were not significantly associated with patient survival. Interestingly, combined evaluation revealed that the group with the MUC1-negative plus p53-negative expression pattern showed a better prognosis than the remaining cases. In contrast, the group with the MUC2-negative plus p53-positive pattern showed a worse prognosis. CONCLUSIONS: Mucin expression is altered in gastric adenoma and carcinoma, and MUC1 mucin expression is significantly associated with poorer outcome in gastric carcinomas. A MUC1-negative plus p53-negative pattern or a MUC2-negative plus p53-positive pattern may predict outcome in patients with gastric carcinomas.

Adenoma↗

PubMed2001

Antimetastatic and antitumor effects of benzoquinonoid AC7-1 from Ardisia crispa.

An antimetastatic and cytostatic substance, termed AC7-1, was isolated from Ardisia crispa and identified as a benzoquinonoid compound, 2-methoxy-6-tridecyl-1,4-benzoquinone. It was originally characterized as the potent PAF (platelet-activating factor) receptor-binding antagonist with nonspecific antiplatelet effects on platelet aggregation induced by various agonists including PAF, ADP, thrombin and collagen. The nonspecific antiaggregatory properties of AC7-1 drew our interest given its possible relationship in integrin receptor-binding antagonistic activity. The integrin receptor plays an important role in metastasis and thrombosis as the cell surface transmembrane protein. Based on the aforementioned facts, the antimetastatic activities of AC7-1 were examined using various in vitro and in vivo metastasis assays. AC7-1 strongly blocked B16-F10 melanoma cell adhesion to extracellular matrix (ECM) and B16-F10 melanoma cell invasion. AC7-1 also remarkably inhibited pulmonary metastasis and tumor growth in vivo. AC7-1 inhibited B16-F10 melanoma cell adhesion to only specific synthetic peptides including RGDS. These findings suggest that antimetastatic activities of AC7-1 can be caused by blocking integrin-mediated adherence. We found AC7-1 to be a potential candidate for the development of a new antimetastatic drug.

Animals↗

PubMed2001

Genetic alterations in gallbladder adenoma, dysplasia and carcinoma.

Adenoma and dysplasia in the gallbladder (GB) have been reported as precancerous lesions, but the genetic evidence of this is not clearly defined. The purpose of this study was to analyze the frequencies of K-ras, p53, and p16 gene mutations, of microsatellite instability (MI) and of loss of heterozygosity (LOH) in GB cancer, dysplasia, and adenoma. Tissues from 15 GB cancers, five dysplasias around cancerous tumors, and three adenomas were collected prospectively. The mutation rates of K-ras, p53, and p16 were 20.0, 35.7, and 30.7%, respectively, in GB cancers. However, no mutations were found in dysplasia or adenoma. Reduced staining for p16 was seen in 23% of carcinomas. All of the GB carcinomas and four out of five (80%) of the dysplasias showed LOH in a minimum of one locus, but one out of three (33%) cases of adenoma displayed LOH in only one locus. All of the loci of LOH in the dysplasias, except one, showed the same patterns of allelic loss as the adjacent carcinomas. Only one dysplasia showed multiple MI. In conclusion, multiple LOH may be associated with the development of dysplasia and the malignant transformation of GB carcinoma. Gene alterations of K-ras, p53, and p16 are important steps in the malignant changes of dysplasia. However, MI seems to have only a limited role in GB cancer development.

Adenoma↗

PubMed2001

Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas.

Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric carcinomas were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis. To correlate DNA and RNA lesions of the FHIT gene with the effect on FHIT protein expression, we have investigated the FHIT gene for loss of heterozygosity (LOH), aberrant transcripts, point mutations, and protein expression in 35 gastric adenocarcinomas. Allelic loss at D3S1300 was detected in 7 of 33 (21%) informative cases. Aberrant transcripts, with deletions and/or insertions, were observed in 20 of 35 (57.1%) cases and resulted from alternative splicing through exon skipping and/or insertion of the FHIT intron 5 sequence or activation of the cryptic splice site. Point mutations were not found in the FHIT coding region but detected in noncoding exon 2, 3, 4, or 5 of eight aberrant transcripts. Significant reduction of FHIT protein expression was observed in 22 of 35 (62.9%) cases. Aberrant FHIT transcription was shown to be associated with loss of FHIT protein expression. However, aberrant FHIT transcripts themselves were not associated with any clinicopathological parameters, such as age, sex, tumor site, or clinical stage. Moreover, there was no association between the presence of LOH at D3S1300 and the expression of aberrant FHIT transcripts. Nevertheless, high frequency of aberrant FHIT transcripts, significant rate of LOH at D3S1300, and altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.

Acid Anhydride Hydrolases↗

PubMed2001

[Tissue array technology for translational research. From gene discovery to application].

Large scale scanning of the human genome has become possible with the introduction of DNA microarray. The ability to survey the expression of up to 5000 to 50,000 genes in a single experiment provides significant new opportunities, as well as new challenge. It will be important to translate genomic scale information on cancer biology to functional or clinical application. This requires prioritization of hundreds of targets discovered, functional validation of these targets, as well as a thorough knowledge of the involvement of the candidate target genes in vivo in human tissue. We have developed a tissue array technology for genome scale expressional and clinical cancer research. This technology enables high-throughput molecular analysis of large number of specimens. Our tissue arrays are constructed by arranging the cylindrical biopsies of 2.0 mm diameter from 60 individual tumor tissues into a tissue array block, which is then sliced into 200 or more identical slides for probing RNA or protein targets. A single immunohistochemistry or in situ hybridization experiment provides information on all 60 specimens on the slides, while subsequent sections can be analyzed with other probes or antibodies. We produced gastric cancer tissue array slides with various kinds of subsets, including 600 subsequent cancer cases, 100 preneoplastic lesions, 60 metastatic lesions, 60 synchronous cancers, 60 metachronous cancers, 60 young age patients, and 120 familial cases. We searched the presence of Epstein-Barr virus in those cancer specimens. We also applied 10 antibodies in those samples and stratify the prognostic significance of these antibodies. Tissue array technology expand the scope of high-throughput molecular analysis of archival tissue specimens with multiple probes for specific genes or proteins for functional or clinical application.

Antibodies↗

PubMed2001

CpG island methylation in premalignant stages of gastric carcinoma.

There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Altered expression and mutation of beta-catenin gene in gastric carcinomas and cell lines.

beta-catenin serves not only as a structural component of the E-cadherin-mediated cell-cell adhesion system, but also as a signaling molecule of the Wnt/wingless pathway. Deregulated expression of beta-catenin and mutations of the gene have been identified in a number of human malignancies. To determine the role of beta-catenin defects in stomach cancer, we investigated beta-catenin exon 3 mutations and altered protein expression in 77 primary gastric carcinomas and 11 cell lines. In addition, the immunohistochemical expression pattern of beta-catenin in 303 consecutive gastric cancers was determined and their relationships with clinicopathologic features and patient outcome were investigated. This study revealed 5% (4 of 77) tumors and 27% (3 of 11) cell lines with beta-catenin gene alteration, 6 missense mutations, and 1 interstitial deletion. These genetic changes were shown to correlate closely with nuclear localization of the protein (p = 0.001). In an immunohistochemical analysis, abnormal expressions of beta-catenin, such as nuclear accumulation and loss of membranous distribution, were detected in 27% (81 of 303) of tumors overall. These altered beta-catenin expressions were more commonly observed in 37% (58 of 158) diffuse type gastric carcinomas (p < 0.001). Loss of membranous beta-catenin staining was associated with poor survival (p = 0.045). In conclusion, our results demonstrate that beta-catenin mutations are common in gastric cancer cell lines but occur infrequently in gastric carcinoma tissues. These mutations are one of the causes of the nuclear accumulation of beta-catenin. Frequent abnormalities of beta-catenin expression in gastric carcinoma support the idea that both structural and signaling functions of the protein play a critical role in gastric carcinogenesis.

Adolescent↗

PubMed2001

Assessment of markers for the identification of microsatellite instability phenotype in gastric neoplasms.

We tested three mononucleotide, 45 dinucleotide, and five tetranucleotide repeats in 30 gastric adenomas and 30 gastric carcinomas for microsatellite instability (MSI) in order to evaluate which microsatellites might indicate the MSI status in gastric neoplasms. Along with the increase in tested markers, the proportion of low-frequency MSI (MSI-L) tumors increased. On immunohistochemistry, MSI-L gastric neoplasms did not show any alteration in hMLH1 or hMSH2 protein expression, while most of the high-frequency MSI (MSI-H) tumors did show alterations in the above mismatch repair proteins. The above findings suggested that MSI-L tumors cannot be distinguished from microsatellite stable tumors. Two mononucleotides, BAT25 and BAT26, were sufficient for the screening of MSI. An additional three dinucleotides, D17S786, D6S105 and D19S188, were also highly sensitive and specific in identifying MSI phenotype tumors.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Microsatellite instability in synchronous gastric carcinomas.

Synchronous gastric carcinomas are found in 4% to 10% of all gastric carcinomas, and the tumor multiplicity is believed to be related to genetic predisposition. To investigate the role of mismatch repair error in synchronous gastric carcinomas, we analyzed the microsatellite instability (MSI) status of 101 cancers from 48 gastrectomy specimens and compared them with 149 solitary gastric carcinomas. Multiple synchronous gastric carcinomas are characterized by slightly older age, predominance in males, early stage and lower lymph node metastasis. Among the 48 cases, 8 (18 lesions) were associated with a gastric adenoma (type I) and 40 (83 lesions) were not associated with a gastric adenoma (type II). The MSI+ rate was 50% in the type I and 8.4% in the type II synchronous gastric carcinomas (p < 0.001), while that of solitary gastric carcinomas was 9.4%. In addition, the frameshift mutation rates of the TGF-betaRII, BAX and hMSH3 genes in the type I synchronous carcinomas were higher than those in the type II synchronous carcinomas. These findings indicate that a defect in the mismatch repair system might play a role in the carcinogenesis of a minor subset of multiple gastric carcinomas associated with adenomas.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Association of p53 and BCL-2 expression with Epstein-Barr virus infection in the cancers of head and neck.

BACKGROUND: Reports that have both evaluated the site-specific Epstein-Barr virus (EBV) infection and compared it with the expression of the EBV-related proto-oncogenes and tumor suppressor genes in the various cancers of head and neck are scarce. METHODS: Thirty-eight nasopharyngeal carcinoma (NPC) cases, 32 oropharyngeal or hypopharyngeal carcinoma (OPC/HPC) cases, and 93 laryngeal carcinoma (LC) cases were evaluated with in situ hybridization on EBV-encoded small RNA (EBER) and immunohistochemical assessments of the p53, bcl-2, and epidermal growth factor receptor (EGFR) by use of formalin-fixed paraffin-embedded tissue array slides. RESULTS: The expression of viral EBERs was observed in more than two thirds (71.1%) of the NPC cases. In contrast, only 1 case of OPC and none of the HPC or LC cases exhibited EBV positivity. In the nonkeratinizing NPC, the EBV positivity was significantly associated with both frequent p53 overexpression (p =.033) and bcl-2 expression (p =.001). In the EBV-positive nonkeratinizing NPC, a correlation between p53 overexpression and the tumor infiltration lymphocyte (TIL) density was noted (p =.012). CONCLUSIONS: A site-specific expression of viral EBER was demonstrated in the head and neck cancers, which suggests an important role for both p53 and bcl-2 in the carcinogenesis of an EBV-infected NPC. The correlation between p53 overexpression and the TIL density in the EBV-infected NPC suggests that the product of a lymphoepithelial interaction, such as A20, can induce a dysfunctional p53 protein.

Adolescent↗

PubMed2001

Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.

The mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the possible mechanisms. We attempted to demonstrate the role of mitogen-activated protein (MAP) kinases, generally considered to be important mediators of proliferative and apoptotic signals, in NSAID-induced colon cancer cell apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion method. MAP kinase activation was assessed by Western blot using phosphospecific antibodies to MAP kinases. Kinase assay using activating transcription factor-2 (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole compound (SB203580) was utilized. Caspase-3 activity was measured using the tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis. From these results, we conclude that NSAIDs can induce prolonged activation of MAP kinases in colon cancer cells and that, of these, p38 MAP kinase may play a partial but significant role in indomethacin-induced apoptosis.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication.

BACKGROUND/AIMS: We earlier reported that N-carbamoyl-L-glutamate (CG) plus L-arginine (Arg) protected normal and 70% hepatectomized rats from intoxication by a lethal or sub-lethal dose of ammonium acetate, respectively. In the present study, the protective effect of these compounds on cirrhotic rats was assessed. METHODS: CG plus Arg were administered prior to the injection of a sub-lethal dose of ammonium acetate into dimethylnitrosamine-induced cirrhotic rats. Control rats were given phosphate-buffered saline (PBS) instead of the mixture. The behavior of the rats was monitored until the time of sacrifice. Blood ammonia level, blood urea nitrogen (BUN) and liver carbamoylphosphate synthetase I (CPS I) activity were determined. RESULTS: Pretreatment of rats with the mixture of CG plus Arg could significantly lower the blood ammonia level (P<0.05), increase the activity of CPS I (P<0.05), improve abnormal behavior associated with ammonia intoxication (P<0.05), and increase BUN (P<0.05), as compared with the PBS-injected control group. There were significantly close correlations between (1) the increase of CPS I activity; (2) the improvement of abnormal behavior; (3) the increase of BUN; and (4) the decrease of the blood ammonia level. CONCLUSIONS: A mixture of CG plus Arg could protect rats with liver cirrhosis from acute ammonia intoxication.

Acetates↗

PubMed2001

Microsatellite instability in double primary cancers of the colorectum and stomach.

Little is known about genetic alterations of patients who present multiple primary cancers. We hypothesized that microsatellite instability (MSI) is one of the underlying genetic factors in the development of double primary cancers in colorectal cancer patients. We examined for MSI in 41 colorectal cancer patients who presented with extra-colonic primary cancers consisted of 17 gastric and 24 non-gastric cancers. Coincident MSI+ in tumors of two organs were observed in 3 (17.7%) of 17 patients with colon and stomach cancers and 0 of 24 patients with colon and non-gastric cancers (P =.03). In 17 patients with colon and stomach cancers, 6 (31.6%) of 19 colon cancers and 3 (17.7%) of 17 gastric cancers exhibited MSI+. Among four patients with metachronous colon cancers who were identified within the 41 double primary cancer patients, two patients were associated with the MSI+ phenotype. In summary, the prevalent coincidence of MSI suggests that genetic defect of mismatch repair deficiency may be responsible for a small subset of double primary cancers of the colorectum and stomach.

Aged↗

PubMed2001

Influence of the number of lymph nodes examined on staging of gastric cancer.

BACKGROUND: Nodal staging for gastric cancer according to the 1997 Union Internacional Contra la Cancrum tumour node metastasis classification is based on the number of metastatic lymph nodes. The aim of this study was to evaluate whether the number of lymph nodes examined affected staging of gastric cancer. METHODS: A retrospective study was performed in 4789 consecutive patients with gastric cancer, who had undergone curative resection (R0) from 1986 to 1995. Patients were classified according to the number of nodes examined. The number of metastatic lymph nodes and stage-stratified survival were compared. RESULTS: There were significant differences in the number of metastatic lymph nodes and survival in stage IIIA between patients with 15 or more lymph nodes and those with fewer than 15 nodes. In analysis restricted to patients with 15 or more nodes, stage-stratified survival did not vary significantly with lymph node yields for any stage except IIIB, in which there was a significant difference between the subgroup with fewer than 20 examined lymph nodes and patients with 35 or more nodes. CONCLUSION: The number of lymph nodes examined did not significantly affect node staging of gastric cancer as long as at least 15 nodes were examined. For stage IIIB, more than 15 lymph nodes may be required for optimal staging.

Adult↗