National Cancer Institute®
Last Modified: March 1, 2002
UI - 11760076
AU - Yasui W; Oue N; Kuniyasu H; Ito R; Tahara E; Yokozaki H
TI - Molecular diagnosis of gastric cancer: present and future.
SO - Gastric Cancer 2001;4(3):113-21
AD - First Department of Pathology, Hiroshima University School of Medicine, Japan.
Although histopathological diagnosis is extremely useful for the definitive as well as the supportive diagnosis of gastric cancer in clinical practice, it is limited in certain respects. Over the past 15 years, integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. These abnormalities, which include telomerase activation, genetic instability, and abnormalities in oncogenes, tumor suppressor genes, cell-cycle regulators, cell adhesion molecules, and DNA repair genes, could be effective markers in the molecular diagnosis of gastric cancer. It is possible that the molecular analysis of these alterations in histopathology specimens may overcome deficiencies in diagnoses that depend only on histomorphology, and, consequently, we may be able to improve the differential diagnosis of cancer, obtain information on the grade of malignancy, and identify patients at high risk of developing multiple primary cancers. In Hiroshima, we have established a system of molecular-pathological diagnosis as a routine service; about 5,000 lesions of the stomach have been subjected to this diagnosis, and much useful information has been obtained. In the near future, genetic analysis by means of DNA microarray may become routine in the diagnosis of gastric cancer. Genetic analysis of histopathology specimens may make clear the characteristics of individual cancers; indicating the common and specific features of molecular pathogenesis that may be directly connected with gene therapy or molecular-targeted therapy. By analyzing the relationship between single-nucleotide polymorphisms and cancer susceptibility, we will be able to obtain information on cancer prevention from histopathology samples.
UI - 11760077
AU - Tani M; Takeshita K; Inoue H; Iwai T
TI - Adequate endoscopic mucosal resection for early gastric cancer obtained from the dissecting microscopic features of the resected specimens.
SO - Gastric Cancer 2001;4(3):122-31
AD - First Department of Surgery, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
BACKGROUND: We have employed endoscopic mucosal resection (EMR), using a cap-fitted panendoscope (EMRC), for early gastric cancer since 1992. The presence of an adequate surgical margin is a requirement because of the radicality of EMR, and dissecting microscopic examination is useful in regard to the diagnosis of spread of the disease. METHODS: To devise an adequate method of EMR that allows no lateral residue, we examined gastric mucosal specimens obtained by EMRC. One hundred and sixty-seven specimens from 97 lesions in 85 patients treated by EMRC were examined in regard to characteristic features, the recovery of marks made around the lesion, and the frequency of residue, and comparisons were made between the dissecting microscopic and histopathological findings. RESULTS: The first specimen obtained with a large cap under full suction was a circular shape measuring 21 x 19mm. The second specimen from fractionated resection was a half-moon or crescent shape, and the third specimen had a ginkgo leaflike or irregular shape. In the elevated lesions, coincidence regarding the spread, as determined by dissecting microscopy and histopathology, was present in 62 (93%) of the 67 lesions. In 16 (53%) of 30 flat or depressed lesions, there was a difference of 2 to 5 mm between the spread determined by these two examinations. CONCLUSION: It is important to place an adequate number of marks around the lesion and recover all marks by resection. When an elevated lesion measures 15mm or more, and a flat or depressed lesion is not clearly demarcated, aggressive use of planned fractionated resection seems to be the best way to prevent a lateral residue in EMR.
UI - 11760078
AU - Mori Y; Arita T; Shimoda K; Yasuda K; Yoshida T; Kitano S
TI - Effect of periodic endoscopy for gastric cancer on early detection and improvement of survival.
SO - Gastric Cancer 2001;4(3):132-6
AD - Surgery Division, Arita Gastrointestinal Hospital, Oita, Japan.
BACKGROUND: Increases in the detection of early gastric cancer have indisputably, improved long-term survival. The aim of this study was to establish the value of periodic gastric endoscopy and the appropriate intervals for its performance. METHODS: We compared, retrospectively, the clinicopathologic characteristics and outcomes of two groups of patients who had undergone surgical treatment for gastric cancer. Of a total of 361 patients, 106 had undergone endoscopic examination within 2 years before the detection of gastric cancer (group 1), and 255 had either undergone no endoscopic examination or had had endoscopic examination more than 2 years before the detection of gastric cancer (group 2). For the evaluation of survival rate, the patients in each group were classified into two subgroups: group 1a, endoscopic examination within 1 year before detection; group 1b, endoscopic examination more than 1 year and within 2 years; group 2a, endoscopic examination more than 2 years and within 4 years before detection; and group 2b, endoscopic examination more than 4 years before detection, or no endoscopic examination. RESULTS: Gastric cancer in group 1 was characterized by small tumor size, no tumor invasion beyond the submucosa, few instances of lymphatic and vascular permeation, and few lymph node metastases. The 5-year survival rate for group 1 patients (96.5%) was significantly higher than that for group 2 patients (71.0%; P < 0.01). The survival rates for group 1a patients and group 1b patients were not significantly different (P = 0.4595). The survival rate for patients in group 2a was significantly lower than that for those in group 1a (P < 0.05). CONCLUSION: Periodic gastric endoscopy enables early detection of cancer, thereby improving survival. The optimal interval for periodic examination appears to be 2 years.
UI - 11760079
AU - Mafune KI; Tanaka Y; Suda Y; Izumo T
TI - Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European-American lymphoma classification.
SO - Gastric Cancer 2001;4(3):137-43
AD - Division of Abdominal Surgery Saitama Cancer Center Hospital, Japan.
BACKGROUND: The best treatment for patients with non-Hodgkin's lymphoma (NHL) of the stomach is still uncertain. The revised European-American lymphoma (REAL) classification has helped to define new, potentially more appropriate classification schemes for gastric lymphomas. METHODS: Fifty-one resected gastric lymphomas were reclassified according to the REAL classification, and the efficacy of multimodal treatment was examined retrospectively. The principal treatment plan consisted of: (1) surgical resection of the stomach with lymph node dissection, followed by (2) systemic chemotherapy, mainly using the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen. RESULTS: According to the Ann Arbor classification, 27 patients had stage IE, 19 had stage IIE, and 5 had stage IV NHL. Using the REAL classification, we diagnosed diffuse large B-cell lymphoma (DLBL) in 23 patients, marginal zone B-cell (low-grade mucosa-associated lymphoid tissue [MALT]-type) lymphoma in 22, follicle center lymphoma in 4, mantle cell lymphoma in 1, and peripheral T-cell lymphoma in 1 patient. Nine of the 51 patients relapsed, and 8 patients with DLBL died of cancer. Survival rates at 5 years after surgery were 96.0% for stage IE, 83.3% for stage IIE, and 87.0% for all patients. Univariate analysis indicated that the tumor histology (according to the REAL classification), depth of invasion, degree of nodal involvement, Ann Arbor staging, and chemotherapy had an impact on patient outcome (P = 0.0018; P = 0.0002; P = 0.0308; P = 0.0016, and P = 0.0118, respectively). CONCLUSIONS: These data reveal that gastric NHL, especially of the low-grade MALT-type, often remains localized and has a good prognosis after surgery. The REAL classification was useful for classifying new categories of NHL, including the MALT-type, in the clinical setting, and for determining the optimal treatment modality for gastric NHL.
UI - 11760081
AU - Kumagai K; Tanaka T; Yamagata K; Yokoyama N; Shimizu K
TI - Liver metastasis in gastric cancer with particular reference to lymphatic advancement.
SO - Gastric Cancer 2001;4(3):150-5
AD - Department of Surgery, Toyosu Hospital, Showa University, Tokyo, Japan.
BACKGROUND: We have previously reported that, in models of mesenteric lymph vessel obstruction in rats, we observed lymphaticovenous communication. This suggested that cancer cells metastasized to the liver by a lymphatic route. In the present study, we investigated the relationship between liver metastasis and lymphatic involvement in gastric carcinoma by examining resected specimens. METHODS: Twenty gastric cancer patients who had synchronous liver metastasis and 17 who developed metachronous liver metastasis after gastrectomy, performed between 1985 and 1997, were included in this study. They were compared with 44 advanced gastric cancer patients who had neither synchronous nor subsequent liver metastasis, and who survived with a disease-free course for more than 5 years. We compared the patients' clinicopathological features; in particular, we investigated extranodal invasion in the resected lymph nodes. This invasion was classified according to the pattern of extranodal cancer invasion, with or without rupture of the lymph node capsule. RESULTS: Liver metastasis was more frequent in patients with extranodal invasion than in those without extranodal invasion (P < 0.002). Multivariate analysis revealed that the correlation between extranodal invasion and liver metastasis was significant (P < 0.024); the odds ratio was 4.412. Metastasis to the lymph nodes was the next most significant risk for liver metastasis. CONCLUSION: We consider that the lymphatic system is closely related to the establishment of liver metastasis; in particular, extranodal invasion is a significant risk factor for liver metastasis in patients with gastric cancer.
UI - 11712083
AU - Ikeguchi M; Kaibara N
TI - Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer.
SO - Int J Mol Med 2001 Dec;8(6):661-6
AD - First Department of Surgery, Faculty of Medicine, Tottori University, Yonago, Japan. firstname.lastname@example.org
Survivin is a member of the inhibitor of apoptosis protein (IAP) family. The expression of survivin has not been reported in differentiated normal tissues, but it has been observed in many cancerous tissues. Recent studies have revealed that survivin may correlate with the chemo-radio resistance of certain malignant cells. In the present study, the correlation between the occurrence of apoptosis and the level of expression of survivin messenger RNA (mRNA) was investigated in a gastric cancer cell line (MKN-45) and in patients with advanced gastric cancer during cisplatin (CDDP) treatment. In the gastric cancer cell line, the percentage of apoptotic cells (apoptotic index: AI) did not change after 48 h incubation with low-dose CDDP (1 microg/ml), whereas the AI explosively increased between 12 and 24 h treatment with high-dose CDDP (10 microg/ml). Relative levels of expression of survivin mRNA and survivin protein increased after low- and high-dose CDDP treatment. Survivin mRNA was not detected in normal gastric mucosas. Also, in 13 patients with advanced gastric cancer who underwent CDDP-based preoperative chemotherapy, survivin mRNA was detected in only 2 cases (15.4%). Survivin mRNA was observed in the resected tumor specimens of two cases. No significant correlation between survivin mRNA expression and the occurrence of apoptosis in resected tumors or between survivin mRNA expression and patient survival was observed. These findings indicate that survivin may play an important role for the chemoresistance of this cancer cell line. However, the clinical importance of survivin expression remains unclear in patients with gastric cancer.
UI - 11822008
AU - Lambert R
TI - Diagnosis of esophagogastric tumors.
SO - Endoscopy 2002 Feb;34(2):129-38
AD - International Agency for Research on Cancer, Lyon, France. email@example.com
There is increasing concern regarding the need to establish guidelines for upper gastrointestinal endoscopy. This applies to the reliability of the diagnosis of early cancer, tolerance, and the need to reduce the use of conscious sedation in order to contain costs--one reason why nasogastroscopy with a thin fiberscope is being applied with increasing success. Recent advances that have been made in the early diagnosis of esophageal and gastric tumors now require high-resolution video gastroscopes and the routine use of chromoscopy. For a long time, the helpful contribution made by the zoom video endoscope to the identification of the pit pattern in neoplastic lesions was limited to the colon. However, the most recent zoom endoscopes, with improved mechanical characteristics and a standard diameter, have now opened up relevant applications in the analysis of early esophageal or gastric malignancies. The best example of this is the identification of the pit pattern in intestinal metaplasia in Barrett's esophagus, although the classification of the pit pattern in upper gastrointestinal neoplasia is still being investigated. Spectroscopic analysis of the response of neoplastic tissue to an applied photon beam has been hampered by the complex origins of the efferent photons. Recent technology, available only through a physical laboratory allows simultaneous analysis of fluorescence, reflectance, and light scattering. In this situation, the method has obtained sensitivity and specificity rates of nearly 100% in classifying low-grade dysplasia, high-grade dysplasia, and cancer in Barrett's esophagus. With regard to depth exploration in the wall of the digestive tract, endosonographic examination using a high-frequency probe (20-30 MHz) may be challenged in the future by the technique of optical coherence tomography, a method that does not require acoustic transmission through water and provides a much higher resolution, of up to 10 microm. Optical coherence tomography could be used in the staging of intramucosal esophageal cancer and for detecting intestinal metaplasia in the esophagus. In conclusion, the increasing progress being made in the accuracy of endoscopic diagnosis emphasizes the need for cost-benefit analyses of screening and surveillance protocols.
UI - 11821786
AU - Mori M; Mimori K; Yoshikawa Y; Shibuta K; Utsunomiya T; Sadanaga N;
TI - Tanaka F; Matsuyama A; Inoue H; Sugimachi K Analysis of the gene-expression profile regarding the progression of human gastric carcinoma.
SO - Surgery 2002 Jan;131(1 Suppl):S39-47
AD - Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
BACKGROUND: Tumor tissue consists of a variable mixture of tumor and host-cell populations. Recent developments in laser microdissection (LMD) and cDNA microarray analysis have encouraged us to study the differential gene expression profiles among normal cells, primary carcinoma cells, and metastatic carcinoma cells in cases of gastric carcinoma. METHODS: Total RNA was extracted from the cells obtained by means of LMD from the primary carcinoma, the corresponding gastric epithelium, and the lymph node metastasis in 5 cases of primary gastric carcinoma. RNA was amplified by the T7-based amplification system to be applied to a cDNA microarray. Thereafter, the differentially expressed genes among the 3 populations were evaluated. RESULTS: cDNA samples for microarray studies were successfully obtained from each cell population of 5 cases. The cDNA microarray demonstrated that several interesting genes, such as cell-cycle regulators and growth factors, were overexpressed in the metastatic cells compared with in the primary carcinoma cells. Oncogenes and cell-adhesion molecules were more overexpressed in the primary carcinoma cells than in the normal cells. On the other hand, caspase 8 and cadherin were more suppressed in the primary carcinoma cells than in the normal cells. Interestingly, among the matrix metalloproteinase family, only MMP7 was identified as a differentially overexpressed gene in both the primary carcinoma and the metastatic cells in comparison with the normal cells. CONCLUSIONS: This study demonstrated that the combined use of LMD, T7-based amplification, and a cDNA microarray enabled us to identify genes directly associated with each population of tumor tissue. The method will open up new possibilities for the precise gene analysis of tumor progression and metastasis.
UI - 11821789
AU - Baba H; Korenaga D; Kakeji Y; Haraguchi M; Okamura T; Maehara Y
TI - DNA ploidy and its clinical implications in gastric cancer.
SO - Surgery 2002 Jan;131(1 Suppl):S63-70
AD - Department of National Kyushu Cancer Center, Fukuoka, Japan.
BACKGROUND: Biological characteristics of gastric cancer depend mostly on genetic alterations in the cancer cells of individuals. To precisely predict the biological behavior and clinical outcome of individual cancer, it may be important to clarify the DNA profiles of cancer cells in each case. METHODS: We have reviewed the most important results of studies on DNA ploidy of gastric cancer published in the English literature during the last 2 decades. RESULTS: Gastric carcinoma with aneuploidy has been shown to have a high proliferative activity and a high metastatic or invasive potential, thus leading to a poor prognosis as compared to diploid tumors. CONCLUSION: Analyses of DNA ploidy in gastric cancer may provide clinically useful information on diagnostic, therapeutic, and prognostic aspects. Further investigations may be needed to clarify the relationship between chromosome instability and DNA ploidy.
UI - 11821790
AU - Kabashima A; Maehara Y; Koga T; Kakeji Y; Sugimachi K
TI - The biologic features of intramucosal gastric carcinoma with lymph node metastasis.
SO - Surgery 2002 Jan;131(1 Suppl):S71-7
AD - Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
This review concentrates on the clinicopathologic studies and molecular biologic studies of intramucosal gastric carcinomas (IMGCs) with lymph node metastasis that have been published to date. There have been several reports in which IMGCs with lymph node metastasis were compared with IMGCs without lymph node metastasis from the view of clinicopathologic features. However, there have been a few reports in which IMGCs with lymph node metastasis were compared with IMGCs without lymph node metastasis from the view of molecular biologic features. In general, IMGCs with lymph node metastasis have been commonly reported to be large lesions, poorly differentiated adenocarcinoma, and associated with peptic ulcer, in comparison with IMGCs without lymph node metastasis. Regarding genetic studies or molecular biologic studies, only DNA distribution pattern, proliferative cell nuclear antigen and the monoclonal antibody Ki-67, or matrix metalloproteinases 2 and 9 have been investigated in IMGCs with lymph node metastasis. The malignant potential of the carcinoma cells cannot been evaluated by a clinicopathologic study with the use of hematoxylin and eosin staining. It may be unavoidable that minimal operation is widely accepted for the treatment of IMGCs. It may be more essential to establish the staging by both clinicopathologic and molecular biologic examinations to rule out the presence of IMGCs with lymph node metastasis.
UI - 11821792
AU - Maehara Y; Kakeji Y; Koga T; Emi Y; Baba H; Akazawa K; Sugimachi K
TI - Therapeutic value of lymph node dissection and the clinical outcome for patients with gastric cancer.
SO - Surgery 2002 Jan;131(1 Suppl):S85-91
AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BACKGROUND: While the incidence of gastric cancer differs greatly between Japan and other countries, both diagnostic and treatment modalities for patients with gastric cancer have improved in Japan. What follows is an overview of the effects of lymph node dissection for such patients. METHODS: We analyzed data on 2152 Japanese men and women with gastric cancer who underwent surgical resection from 1965 to 1995 at Kyushu University in Fukuoka, Japan. We focused on time trends of surgical management, including lymph node dissection and postoperative outcome. RESULTS: In all cases of gastric cancer, the rate of early gastric cancer increased from 18% in the first 6-year period to 57% in the last 5-year period. Extensive lymph node dissections (D2 and D3) were performed more frequently in recent years. Due to early identification of the cancer and upgraded perioperative care, both postoperative morbidity and mortality rates 30 days after surgery have decreased greatly, even in aged patients. CONCLUSIONS: Early tumor detection, standardized surgical treatment, including routine lymph node dissection, and improved perioperative management have led to increased survival time among patients with this malignancy.
UI - 11776129
AU - Wu Q; Chen Z; Su W
TI - Mechanism of inhibition on activator protein-1 activity by all-trans retinoic acid in gastric cancer cells.
SO - Chin Med J (Engl) 2000 Nov;113(11):972-6
AD - State Laboratory for Tumor Cell Engineering, Xiamen University, Fujian 361005, China.
OBJECTIVE: To determine the mechanism of all-trans retinoic acid (ATRA) on growth inhibition in human gastric cancer cells. METHODS: Gastric cancer cell lines: MGC80-3, BGC-823, SGC-7901 and MKN-45. CAT assay, Northern blot, Western blot, gene transfection and MTT assay. RESULTS: ATRA can inhibit the activator protein-1 (AP-1) activity in ATRA-sensitive cell lines, but not in ATRA-resistant cell line, and the anti-AP-1 activity of ATRA is mediated by its receptor, retinoic acid receptor alpha (RAR alpha). ATRA can also inhibit the expression of cJun and cFos. One of the mechanisms for ATRA to inhibit the growth of gastric cancer cells may be through its inhibitory effect on the AP-1 activity and its influence on up-regulation of RAR alpha expression. The inhibition of cJun and cFos expressions by ATRA may also contribute to the anti-AP-1 activity. CONCLUSIONS: ATRA inhibits the growth of gastric cancer cells through the regulation of AP-1 activity. This action is mediated by RAR alpha.
UI - 11776130
AU - Zhao Y; Xiao B; Chen B; Qiao T; Fan D
TI - Upregulation of drug sensitivity of multidrug-resistant SGC7901/VCR human gastric cancer cells by bax gene transduction.
SO - Chin Med J (Engl) 2000 Nov;113(11):977-80
AD - Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
OBJECTIVE: To investigate the role of bax in a vincristine (VCR)-induced multidrug-resistant (MDR) human gastric cancer cell line, SGC7901/VCR, in which the Bax protein expression level was significantly lower compared with that in parent cells. METHODS: A bax eukaryotic expression vector was constructed and transfected into SGC7901/VCR cells by lipofectamine, and resistant clones were selected by G418. Western blotting detected Bax expression in transfectants. Tetrazolium blue (MTT) assay evaluated the differences in drug sensitivity and cell cycle changes of transfectants were analyzed using flowcytometry (FCM). RESULTS: The bax eukaryotic expression vector was constructed and transfected into SGC7901/VCR cells. Through G418 selection, resistant clones were obtained. Western blotting demonstrated that the expression of Bax protein was markedly increased in bax transduced cells. These cells were more sensitive to adriamycin (ADR) and VCR than mock vector transducted cells. Moreover, bax transfection enhanced ADR-induced apoptosis and VCR-induced G2/M phase arrest of SGC7901/VCR cells. CONCLUSION: Bax was involved in the MDR of SGC7901/VCR cells.
UI - 11777208
AU - Kashida H; Kawamata H; Ichikawa K; Morita K; Imura J; Fujimori T
TI - Intracytoplasmic localization of cathepsin D reflects the invasive potential of gastric carcinoma.
SO - J Gastroenterol 2001 Dec;36(12):809-15
AD - Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan.
BACKGROUND: The present study was undertaken to investigate the role of cathepsin D in the invasiveness of human gastric cancer. METHODS: Immunohistochemical cathepsin D staining was performed in samples from 29 early gastric adenocarcinomas (papillary or tubular adenocarcinoma) and 15 gastric adenomas, and their adjacent nonneoplastic gastric mucosa. We classified the patterns of cathepsin D immunostaining into four types; type A, fine granular staining in the apical portion: type B, intense coarse granular staining in the apical portion; type C, fine granular staining in the basal portion; and type D, diffuse granular staining throughout the cytoplasm. RESULTS: All of the nonneoplastic mucosa showed an apical cytoplasmic distribution pattern (type A or type B). However, 20% (2/10) of low-grade gastric adenomas and 60% (3/5) of high-grade gastric adenomas showed an abnormal staining pattern. i.e., types C and D. Moreover, 82% (9/11) definite intramucosal gastric adenocarcinomas, and the majority of gastric adenocarcinomas with submucosal invasion [83% (15/18) of those in the mucosal part and 100% (14/ 14) of those in the invasive submucosal part] showed an abnormal staining pattern (types C and D). Interestingly, most of the carcinoma cells invading the stroma and lymphatics showed the type D staining pattern. CONCLUSIONS: These results indicate that an abnormal cytoplasmic staining pattern of cathepsin D may reflect the invasive potential of gastric carcinoma cells.
UI - 11777209
AU - Chang WK; Kim HY; Kim DJ; Lee J; Park CK; Yoo JY; Kim HJ; Kim MK; Choi
TI - BY; Choi HS; Park KN Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study.
SO - J Gastroenterol 2001 Dec;36(12):816-22
AD - Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
BACKGROUND: Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age. sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. RESULTS: Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10-3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI., 1.01-2.53; P = 0.043). CONCLUSIONS: H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer.
UI - 11810045
AU - Kijima Y; Hokita S; Yoshinaka H; Itoh T; Koriyama C; Eizuru Y; Akiba S;
TI - Aikou T Amplification and overexpression of c-met gene in Epstein-Barr virus-associated gastric carcinomas.
SO - Oncology 2002;62(1):60-5
AD - First Department of Surgery, Center for Chronic Viral Diseases, Kagoshima University, Kagoshima, Japan. firstname.lastname@example.org
To reveal the role of oncogenes in Epstein-Barr virus (EBV)-positive gastric carcinomas, the amplification and overexpression of the c-met gene were examined by a competitive polymerase chain reaction and immunohistochemistry, respectively. The proportion of c-met amplification and overexpression in EBV-positive and -negative carcinomas did not differ significantly. The amplification and overexpression of the c-met gene in EBV-negative gastric carcinomas were significantly associated with upper location, deeper invasion and lymphatic invasion, while in EBV-positive gastric carcinomas a significant correlation with c-met activation was observed only in deeper invasion. However, none of the observed associations of c-met amplification or overexpression with clinicopathological features in the EBV-positive and -negative carcinomas differed significantly in their strength or direction. These results suggest that the amplification and overexpression of c-met gene do not play a different role in the progression and metastasis of EBV-positive and EBV-negative gastric carcinomas. Copyright 2002 S. Karger AG, Basel
UI - 11823704
AU - Green D; Ponce de Leon S; Leon-Rodriguez E; Sosa-Sanchez R
TI - Adenocarcinoma of the stomach: univariate and multivariate analysis of factors associated with survival.
SO - Am J Clin Oncol 2002 Feb;25(1):84-9
AD - Department of Hematology-Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Col. Seccion 16, Tlalpan, 14000 Mexico D.F., Mexico.
Gastric cancer is the most frequent tumor of the digestive tract in Mexico. Most patients are diagnosed at advanced stages, and fatal outcome is expected. One hundred fifty patient charts were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathologic and treatment variables on survival. Most patients (75%) were at advanced stages, harboring poorly differentiated tumors. Surgery, mostly palliative, was performed on 114 patients. Chemotherapy was administered to 47 patients. On univariate analysis, significant prognostic factors were TNM stage, chemotherapy, surgical attempt, performance status, histology, and tumor site (p < 0.001). On multivariate analysis, independent prognostic factors were TNM stage, histology, tumor site, surgical attempt, and chemotherapy (p < 0.01). Median survival for patients with palliative or adjuvant chemotherapy was 11.4 and 10.4 months, respectively, compared with +/- 3 months for patients with no chemotherapy (p < 0.03). Nonsurgical patients receiving chemotherapy survived 5.4 months versus 1.1 months for those without chemotherapy. The favorable influence of chemotherapy persisted after a stratified analysis of subgroups eliminating potential biases. We identified prognostic factors for survival. Chemotherapy should be considered even for advanced-stage patients with either adjuvant or palliative attempts, because we consistently found a favorable impact on the median survival time. However, phase III prospective randomized trials are awaited.
UI - 11857318
AU - Shen B; Ormsby AH; Shen C; Dumot JA; Shao YW; Bevins CL; Gramlich TL
TI - Cytokeratin expression patterns in noncardia, intestinal metaplasia-associated gastric adenocarcinoma: implication for the evaluation of intestinal metaplasia and tumors at the esophagogastric junction.
SO - Cancer 2002 Feb 1;94(3):820-31
AD - Department of Gastroenterology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. email@example.com
BACKGROUND: Barrett esophagus (BE)/Barrett adenocarcinoma and distal gastric intestinal metaplasia (IM)/adenocarcinoma are similar histologically, but they differ in their clinical presentation, epidemiology, and pathogenesis. Differentiating BE from gastric IM and Barrett adenocarcinoma from gastric adenocarcinoma is difficult, especially when IM is short or tumors are large and involve both sides of the esophagogastric junction. Previously, the authors identified unique cytokeratin (CK) immunoreactivity patterns that were associated strongly with BE and Barrett adenocarcinoma. The specificity of CK7 and CK20 (CK7/20) expression patterns in patients with IM-associated gastric adenocarcinoma, which is distinct epidemiologically from BE/Barrett adenocarcinoma, has not been evaluated. The objective of the current study was to evaluate the CK7/20 expression patterns in noncardia, IM-associated gastric adenocarcinoma in a Chinese population with a low risk for BE and esophageal adenocarcinoma and a high risk for Helicobacter pylori infection and gastric carcinoma. METHODS: Endoscopic biopsy specimens of gastric IM and adjacent tumor from 50 consecutive patients with advanced noncardia gastric carcinoma were immunostained for CK7 and CK20. Clinical and endoscopic features and H. pylori status were documented. Two gastrointestinal pathologists, blinded to clinical and endoscopic data, independently assessed CK7/20 immunohistochemistry. RESULTS: H. pylori infection was present in 43 of 50 patients (86%). In the area of IM, patchy CK7 staining was seen in 9 patients (18%), and diffuse CK20 staining was seen in all 50 patients (100%). The BE CK7/20 pattern characterized by CK7 staining in superficial and deep glands and the CK20 staining in surface epithelium was not seen in any of the 50 patients. Only one patient (2%) demonstrated a CK7 positive/CK20 negative immunophenotype characteristic of Barrett adenocarcinoma. The remaining 49 patients (98%) showed non-Barrett adenocarcinoma patterns of CK7/20 staining, i.e., a CK7 positive/CK20 positive pattern was seen in 33 patients (66%), a CK7 negative/CK20 positive pattern was seen in 12 patients (24%), and a CK7 negative/CK20 negative pattern was seen in 4 patients (8%). CONCLUSIONS: In a patient population without risk factors for the development of BE/esophageal adenocarcinoma, the CK7/20 pattern characteristic of BE was not present in gastric IM adjacent to adenocarcinoma, and the CK7/20 pattern characteristic of Barrett adenocarcinoma also was extremely rare. These results support the hypothesis that, despite the presence of intestinalized mucosa in both disorders, BE/Barrett adenocarcinoma and gastric IM/adenocarcinoma are two distinct clinical entities with unique demographic, clinical, and CK immunophenotypic findings. These results may have application to the evaluation of patients with IM and adenocarcinoma arising at the esophagogastric junction. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10215
UI - 11857411
AU - Kono K; Takahashi A; Amemiya H; Ichihara F; Sugai H; Iizuka H; Fujii H;
TI - Matsumoto Y Frequencies of HER-2/neu overexpression relating to HLA haplotype in patients with gastric cancer.
SO - Int J Cancer 2002 Mar 10;98(2):216-20
AD - First Department of Surgery, Yamanashi Medical University, Yamanashi 409-3898, Japan. firstname.lastname@example.org
We have identified that HER-2/neu-derived peptides are naturally processed as tumor rejection antigens recognized by tumor-specific, HLA-A2-restricted cytotoxic T lymphocytes in gastric cancer. To evaluate candidates for immunotherapy using HER-2/neu-derived, HLA-A2-restricted peptides, we examined the frequency of HLA-A2 relating to HER-2/neu overexpression or the infiltrating grade of tumor-infiltrating lymphocytes (TILs) in Japanese patients with gastric cancer. HER-2/neu-overexpressing tumors detected by immunohistochemistry amounted to 19% of primary gastric cancers and HLA-A2-positive patients with gastric cancer were 31% of primary gastric-cancer cases. Finally, gastric-cancer patients with both HLA-A2-positive and HER-2/neu-overexpressing tumors amounted to 6.6% of these cases. There was no significant difference in the infiltrating grade of TILs between gastric cancers overexpressing HER-2/neu and those that did not. The candidate for HER-2/neu-based immunotherapy with HLA-A2-restricted peptides represent a very limited population of Japanese patients. Copyright 2001 Wiley-Liss, Inc.
UI - 11665720
AU - Dunbier A; Guilford P
TI - Hereditary diffuse gastric cancer.
SO - Adv Cancer Res 2001;83():55-65
AD - Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome caused by germline mutation of the gene for the cell-to-cell adhesion protein E-cadherin. The syndrome is dominated by predisposition to the histologically diffuse, poorly differentiated form of gastric cancer. It is not associated with intestinal-type gastric cancer, but families may have an elevated risk of lobular breast cancer. Here, we review the identified families, mutations, and proposed mechanisms by which E-cadherin loss promotes tumorigenesis.
UI - 11793367
AU - Kuniyasu H; Oue N; Wakikawa A; Shigeishi H; Matsutani N; Kuraoka K; Ito
TI - R; Yokozaki H; Yasui W Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer.
SO - J Pathol 2002 Feb;196(2):163-70
AD - Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan. email@example.com
The receptor for advanced glycation end-products (RAGE) is a newly recognized factor regulating cancer cell invasion and metastasis. This study investigated the expression of RAGE in gastric carcinomas and its association with invasion and metastasis. Of eight gastric cancer cell lines examined, seven constitutively expressed RAGE messenger ribonucleic acid (mRNA), MKN45 being the exception. RAGE protein expression of MKN28 cells treated with RAGE antisense S-oligodeoxynucleotide was nine times less than that of sense S-oligodeoxynucleotide-treated cells. Growth of cells under RAGE antisense S-oligodeoxynucleotide treatment was not different from that seen under sense S-oligodeoxynucleotide treatment in MKN28 (a cell line producing high levels of RAGE) and MKN45 (a non-RAGE-expressing cell line). RAGE antisense S-oligodeoxynucleotide treatment suppressed the invasive activity of RAGE-positive MKN28 cells, as estimated by in vitro invasion assay. The number of MKN28 cells invading the type IV collagen-coated membrane under RAGE antisense S-oligodeoxynucleotide treatment was significantly lower than under RAGE sense S-oligodeoxynucleotide treatment (p<0.0001). In contrast, antisense and sense S-oligodeoxynucleotide-treated RAGE-negative MKN45 cells showed no difference. A wound-healing assay showed that no RAGE antisense S-oligodeoxynucleotide-treated MKN28 cells migrated into the scraped area, whereas sense S-oligodeoxynucleotide-treated cells showed many budding nests in the scraped area. Immunohistochemistry of gastric carcinoma tissue showed that 62 (65%) of the 96 cases examined were RAGE-positive and that poorly differentiated adenocarcinomas preferentially expressed RAGE protein (38/42, 90%) (p<0.0001). Strong RAGE immunoreactivity was also correlated with depth of invasion and lymph node metastasis (p<0.0001). RAGE-positive cancer cells tended to be distributed at the invasive front of primary tumours and were detected in all metastatic foci in lymph nodes. In contrast, a major RAGE ligand, amphoterin, was expressed in 82 (85%) of the 96 cases, regardless of histological type and disease progression. RAGE expression appears to be closely associated with invasion and metastasis in gastric cancer. Copyright 2001 John Wiley & Sons, Ltd.
UI - 11837708
AU - Tari A; Kodama K; Kurihara K; Fujihara M; Sumii K; Kajiyama G
TI - Does serum nitrite concentration reflect gastric carcinogenesis in Japanese Helicobacter pylori-infected patients?
SO - Dig Dis Sci 2002 Jan;47(1):100-6
AD - Department of Internal Medicine, Hiroshima Red Cross Hospital, Japan.
This study investigated whether the serum nitrite concentration reflects Helicobacter pylori-induced inflammation and atrophic changes of gastric mucosa. Ninety-seven patients underwent biopsy of both antrum and fundus. Samples were analyzed by the rapid urease test and histopathological examination according to the updated Sydney system. Fasting serum samples from each subject were analyzed for specific IgG Helicobacter pylori antibodies, pepsinogen I and II concentrations, and NO2-/NO3- content. Eleven patients had H. pylori eradicated with proton pump-based triple therapy. There was a strong positive correlation between the Helicobacter pylori density in the gastric mucosa and the serum nitrite concentration, but a negative correlation existed between the atrophic grade of the gastric mucosa and both serum nitrite concentration and Helicobacter pylori density in the gastric mucosa. Serum nitrite concentrations decreased significantly after successful eradication of Helicobacter pylori. Therefore, serum nitrite concentration may be a useful marker for oxidative DNA damage and apoptosis associated with Helicobacter pylori infection.
UI - 11837709
AU - Wang J; Chi DS; Kalin GB; Sosinski C; Miller LE; Burja I; Thomas E
TI - Helicobacter pylori infection and oncogene expressions in gastric carcinoma and its precursor lesions.
SO - Dig Dis Sci 2002 Jan;47(1):107-13
AD - Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-1709, USA.
Although it is fairly well accepted that Helicobacter pylori infection plays a significant role in causing gastric cancer, the exact mechanisms involved in its pathogenesis are unclear. We have examined the relationship between H. pylori infection and oncogene expression in different stages of disease progression from precursor lesions to gastric carcinoma. We used Diff-Quik stain to diagnose H. pylori infection and immunohistochemical stains against c-erbB-2, p53, ras, c-myc, and bcl-2 to determine expression of oncogenes. H. pylori infection was found in all cases of chronic gastritis, atrophic gastritis, intestinal metaplasia, and early gastric carcinoma, and in 16 of 30 (53%) cases of advanced gastric carcinoma. Overexpression of c-erbB-2 was found in 2 (7%) cases of advanced gastric carcinoma, which were H. pylori negative. Suppressor gene, p53, was overexpressed in 3 (30%) cases of intestinal metaplasia, 2 (33%) cases of early gastric carcinoma, and 18 (60%) cases of advanced gastric carcinoma. Of these 18 p53-positive advanced gastric cancer cases, 11 (61%) were H. pylori positive. Expression of ras p21 was found in 4 (40%) cases of H. pylori-negative normal mucosa, 10 (100%) cases of chronic gastritis, 1 (10%) case of atrophic mucosa, 6 (60%) cases of intestinal metaplasia, 2 (33%) cases of nonneoplastic mucosa adjacent to early gastric carcinoma, and 7 (23%) nonneoplastic mucosa adjacent to advanced gastric carcinoma, all of which showed H. pylori. No evidence of expression of either c-myc or bcl-2 was detected in any of the above-mentioned samples. The data suggest that H. pylori infection may increase expression of ras p21 proteins and induce p53 suppressor gene mutation early in the process of gastric carcinogenesis.