Epstein‐Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis

Nakamura, Shotaro; Ueki, Takashi; Yao, Takashi; Ueyama, Toshihiko; Tsuneyoshi, Masazumi

doi:10.1002/1097-0142(19940501)73:9<2239::aid-cncr2820730902>3.0.co;2-#

Cited by 135 publications

(95 citation statements)

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“…A subset of gastric carcinomas, known as lymphoepithelioma-like gastric carcinoma, is known to harbor the EBV genome in a high proportion of cases. [30][31][32] The methylation status has no relation to the histological features of EBV-positive gastric carcinoma. 16) Although methylations of the regions of hMLH1 and CDH1 genes we analyzed in this study cause silencing, 33,34) it has been reported that the regions of the MGMT, p16 INK4a , and RAR-β analyzed in this study do not cause gene silencing.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of multiple genes in gastric carcinoma: Association with histological type and CpG island methylator phenotype

et al. 2003

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Hypermethylation of CpG islands is associated with silencing of various tumor suppressor genes. Recent studies on colorectal and gastric cancer have identified a CpG island methylator phenotype (CIMP), which involves the targeting of multiple genes by promoter hypermethylation. For determination of association between DNA methylation pattern or histological type and CIMP status in gastric carcinoma, CpG islands in the promoters of hMLH1 and CDH1 genes, CpG islands overlapping exon 1 of MGMT and p16INK4a genes, and a non-CpG island in exon 1 of the RAR-β β β β gene were studied. The presence of the CIMP was determined by monitoring five methylated in tumor (MINT) loci in 103 gastric carcinomas. Among the 103 gastric carcinomas, DNA hypermethylation was detected in the following frequencies: 14 (14%) for hMLH1, 26 (25%) for MGMT, 26 (25%) for p16 INK4a , 54 (52%) for CDH1, and 53 (52%) for RAR-β β β β. Forty-two (41%) of 103 gastric carcinomas were positive for the CIMP. CIMP and hypermethylation of p16INK4a gene were found more frequently in intestinal and diffuse-adherent types than in diffuse-scattered type (P = = = =0.013 and 0.017, respectively). In contrast, hypermethylation of the CDH1 and RAR-β β β β genes was more common in the diffusescattered type than in the other types (P = = = =0.008 and 0.007, respectively). In intestinal-and diffuse-adherent-type gastric carcinomas, we found significant associations between the presence of the CIMP and hypermethylation of several genes: hMLH1 (P = = = =0.006), p16 INK4a(P = = = =0.018), CDH1 (P = = = =0.024), and RAR-β β β β (P = = = =0.044). Our overall results suggest that in some intestinal-and diffuse-adherent-type gastric carcinomas, DNA hypermethylation affects non-specific gene promoters concordantly, at least in part, whereas in diffuse-scattered-type gastric carcinoma, DNA hypermethylation affects specific genes such as CDH1 and RAR-β β β β. lterations in DNA methylation patterns, such as hypermethylation of CpG islands, are common changes in human cancers. Hypermethylation of CpG islands in promoters is associated with silencing of various tumor suppressor genes.

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Section: Discussionmentioning

confidence: 99%

DNA methylation of multiple genes in gastric carcinoma: Association with histological type and CpG island methylator phenotype

et al. 2003

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“…27 Briefly, the sections were deparaffinized, been summarized previously. 1,28,29 Among them, nine hydrated, treated with 0.2 normal (N) hydrochloric patients had both gastric lymphomas and adenocarciacid (HCl) for 20 minutes, predigested with 0.3 U pronomas simultaneously, whereas another two teinase K for 15 minutes, refixed in 4% paraformaldelymphoma patients had been previously treated for hyde/phosphate-buffered saline, prehybridized, and gastric adenocarcinoma.…”

Section: Methodsmentioning

confidence: 99%

“…32 The primary has been reported in some cases of primary gastric antibodies, including MIB-1 (Immunotech, Marseille, lymphoma [22][23][24] and adenocarcinoma. [25][26][27] France), bcl-2 (clone 124; Dako, Glostrup, Denmark), In the current study, the authors analyzed 12 cases p53 (PAb1801; Oncogene Science, Uniondale, NY), and of coexisting primary gastric lymphoma and adenocar-H. pylori (B471; Dako, Glostrup, Denmark), were apcinoma in the same patient observed either synchroplied overnight at 4 ЊC, followed by incubation with nously or metachronously to delineate the clinicosecondary biotinylated antibody for 20 minutes, and pathologic and immunohistochemical features, as well a streptavidin-biotin-peroxidase complex reagent was as to assess the possible association with H. pylori and then applied for 20 minutes at room temperature. The EBV in these double malignancies.…”

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Synchronous and metachronous primary gastric lymphoma and adenocarcinoma

Nakamura

Aoyagi

Iwanaga

et al. 1997

Cancer

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RESULTS.Two different tumors were found synchronously in 10 patients (5 with Masatoshi Fujishima, M.D. 2 independent tumors and 5 with contiguous/collision tumors) and metachronously in 2. The size of the lymphomas (mean, 7.2 cm) was larger than that of the adeno-1 Second Department of Pathology, Faculty of carcinomas (mean, 3.6 cm) (P õ 0.005). Histologically, 9 of the 12 lymphomas Medicine, Kyushu University, Fukuoka, Japan.(75%) were mucosa-associated lymphoid tissue lymphomas, and all lymphomas 2 Second Department of Internal Medicine, Facinvaded the deep portion of the submucosa or deeper. Conversely, 10 of the 12 ulty of Medicine, Kyushu University, Fukuoka, adenocarcinomas (83%) were early carcinomas. Six adenocarcinomas were intestiJapan.nal type, whereas the other 6 were diffuse type. The MIB-1 index of the adenocarci-3 First Department of Pathology, School of Mednomas (mean, 50.4%) was higher than that of the lymphomas (mean, 29.3%) (P õ icine, Fukuoka University, Fukuoka, Japan. 0.05). Helicobacter pylori (H. pylori) was documented in all 12 patients, whereasEpstein-Barr virus-encoded RNA 1 was detected in only 2. During the followup period after surgery, 6 patients died, 4 due to adenocarcinoma. The survival probability of all 12 patients appeared to be similar to that of previously reported patients with gastric adenocarcinoma alone, and was significantly worse than that of the 217 patients with gastric lymphoma alone (P õ 0.05).CONCLUSIONS. An H. pylori infection is considered to be associated with the development of these double malignancies. In many such synchronously observed cases, lymphomas may precede carcinogenesis, while the prognosis appears to be more closely associated with the adenocarcinoma than the lymphoma. G astric adenocarcinoma is one of the most common malignancies, whereas primary gastric lymphoma is relatively uncommon, oc-The authors thank Dr. Koh-ichi Ohshima and curring in only 1 -7% of all malignant neoplasms of the stomach. Dr. Akinori Iwashita, Fukuoka University, forThe occurrence of both malignant gastric lymphoma and adenocarcitheir kind cooperation, and Brian T. Quinn for noma in the same patient is very rare, and little is known regarding his critical comments.the clinicopathologic characteristics of such cases. 2-13Address for reprints: Shotaro Nakamura, M.D.,Helicobacter pylori (H. pylori) is believed to play a causative role nocarcinomas but also primary gastric lymphomas, especially those of mucosa-associated lymphoid tissue (MALT) type, are associated

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“…EBV is found in more than 80% of a specific histological variant of gastric carcinoma, variably termed lymphoepithelioma-like carcinoma (LELC), medullary or gastric carcinoma with lymphoid stroma (Nakamura et al, 1994). This variant is characterized by the presence of a poorly differentiated morphology, a circumscribed border, an intense lymphoid reaction and a better prognosis (Watanabe et al, 1976).…”

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Microsatellite instability, Epstein–Barr virus, mutation of type II transforming growth factor β receptor and BAX in gastric carcinomas in Hong Kong Chinese

et al. 1999

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Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is detectable in a wide variety of human cancers. It is particularly seen in patients with the hereditary non-polyposis colon cancer (HNPCC) syndrome, in which the affected individual is at risk of developing carcinoma both at an early age and at a range of sites such as the colon, endometrium, urinary tract and stomach (Aaltonen et al, 1993;Marra and Boland, 1995;Lynch et al, 1996). Germline mutation in one of the DNA mismatch repair genes is responsible for a significant proportion of individuals affected by this syndrome (Fishel et al, 1993;Bronner et al, 1994;Liu et al, 1994;Nicolaides et al, 1994;Papadopoulos et al, 1994). MI has also been detected in a variable proportion of the sporadic form of cancer arising in these organs (Eshleman and Markowitz, 1995).Although gastric cancer, worldwide, is deemed to be both the second most common malignancy and second leading cause of cancer death Pisani et al, 1993), the incidence varies markedly in different populations. The incidence of molecular genetic changes is known to vary; for example, the series of reports from high incidence areas such as Japan, Italy, Portugal and Korea show a range for MI varying from 15% to 39% (Han et al, 1993;Chong et al, 1994;Rhyu et al, 1994;Strickler et al, 1994;Lin et al, 1995;Chung et al, 1996;dos Santos et al, 1996;Ohue et al, 1996;Renault et al, 1996). Although MI was noted in a high percentage of gastric cancers with a positive family history (Akiyama et al, 1996;Keller et al, 1996;Ottini et al, 1997), germline or somatic mutations of the mismatch repetition and repair (MMR) genes were rarely reported (Akiyama et al, 1996;Keller et al, 1996). Thus, the mechanism leading to the mismatch repair failure in gastric carcinomas remains largely unknown.The association between EpsteinÐBarr virus (EBV) and gastric cancer also varies among different populations, with the highest positive association occurring in Caucasian populations (Shibata and Weiss, 1992;Ott et al, 1994) and a low association seen in the Japanese (Tokunaga et al, 1993). EBV is found in more than 80% of a specific histological variant of gastric carcinoma, variably termed lymphoepithelioma-like carcinoma (LELC), medullary or gastric carcinoma with lymphoid stroma (Nakamura et al, 1994). This variant is characterized by the presence of a poorly differentiated morphology, a circumscribed border, an intense lymphoid reaction and a better prognosis (Watanabe et al, 1976). The possible relationship between EBV, MI and LELC is largely unexplored except in one study from Japan, in which all eight EBV-associated gastric cancers were negative for MI (Chong et al, 1994).Previous data have shown that the mutator phenotype conferred by MI has a significant role in carcinogenesis, in which it targets Microsatellite instability, EpsteinÐBarr virus, mutation of type II transforming growth factor β receptor and BAX in gastric carcinomas in Hong Kong Chinese Summary Microsatellite instability (M...

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Epstein‐Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis

Cited by 135 publications

References 39 publications

DNA methylation of multiple genes in gastric carcinoma: Association with histological type and CpG island methylator phenotype

DNA methylation of multiple genes in gastric carcinoma: Association with histological type and CpG island methylator phenotype

Synchronous and metachronous primary gastric lymphoma and adenocarcinoma

Microsatellite instability, Epstein–Barr virus, mutation of type II transforming growth factor β receptor and BAX in gastric carcinomas in Hong Kong Chinese

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