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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Gastric Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
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.
2
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.
3
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.
4
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.
5
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.
6
UI - 11760083
AU - Onate-Ocana LF
TI -
Gastric cancer in Mexico.
SO - Gastric Cancer 2001;4(3):162-4
AD - Gastroenterology Department, National Cancer Institute, Mexico DF.
7
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. masaike@grape.med.tottori-u.ac.jp
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.
8
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.
lambert@iarc.fr
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.
9
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.
10
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.
11
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.
12
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.
13
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.
14
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.
15
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.
16
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.
17
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. ryu23@gf6.so-net.ne.jp
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
18
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.
19
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. shenb@ccf.org
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
20
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. kojikono@res.yamanashi-med.ac.jp
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.
21
UI - 11808132
AU - Tominaga S
TI -
[Stomach cancer]
SO - Nippon Rinsho 2001 Nov;59 Suppl 7():274-81
AD - Aichi Cancer Center.
22
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.
23
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. cooninh@z64.so-net.ne.jp
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.
24
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.
25
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.
26
UI - 11837710
AU - Kubicka S; Claas C; Staab S; Kuhnel F; Zender L; Trautwein C; Wagner S;
TI -
Rudolph KL; Manns M
p53 mutation pattern and expression of c-erbB2 and c-met in gastric
cancer: re
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