<6. Low-prevalence gastritis>
The predominant impact of H. pylori infection has minimised the epidemiological relevance of non-H. pylori gastric inflammatory diseases. The Kyoto international classification details agents potentially involved in inflammatory gastric diseases. These stomach-based inflammatory lesions are distinguished from gastritis due to potential gastric involvement in systemic diseases, which diagnostic and the therapeutic criteria follow those of the causative systemic illness (table 2 and section 2.1.2).
Among the aetiopathogenic agents of inflammation, the WHO International Agency distinguishes communicable (mostly environmental, particularly infectious) from non-communicable (mostly immunomodulated, host-related) agents (table 2 and section 2.1.2). The epidemiological impact of several of these conditions has been difficult to establish and varies according to their diverse definitions, ethnic differences and socioeconomic contexts. Moreover, clinical practice shows that inflammatory gastric lesions without any detectable aetiological agents are common.
A detailed description of the specific phenotypes of low prevalence gastritis is beyond the scope of this consensus. Since diagnostic criteria are not yet established, one should refer to the most updated pertinent literature (가장 최근 update된 참고 문헌). For example, at the time of this writing, no consensus has been reached on the topographic distribution and the numbers of eosinophils or lymphocytes required to make a diagnosis of eosinophilic or lymphocytic gastritis (figure 10). (예를 들어, eosinophilic or lymphocytic gastritis를 진단 하는데 필요한 일정 범위에서의 eosinophils or lymphocytes 수는 아직 consensus가 없음)
Figure 10. Low-prevalence host-related gastritis. A significant number of low-prevalence gastritis is listed among those aetiologically classified as host related. (A) Lymphocytic gastritis in oxyntic mucosa. Intraepithelial small lymphocytes (IELs), immunohistochemically profiled as CD3 positive, infiltrating the superficial epithelium. The usual diagnostic threshold for the number of IELs is 20 IELs per 100 epithelial cells. However, since the normal stomach has essentially no IELs, in clinical practice, a count higher than 10 IELs per 100 epithelial cells can be assumed to represent lymphocytic gastritis. (H&E; original magnification 20×). (B) Collagenous gastritis. A subepithelial collagenous band (≥5 µm in thickness), associated with loss or denudement of the superficial epithelium, is the accepted criterion for the diagnosis of collagenous gastritis. A low-grade mononuclear inflammatory infiltrate, usually in the absence of atrophy, is frequently present (H&E; original magnification 20×). (C) Eosinophilic gastritis (EoG). Antral mucosal specimen featuring a dense eosinophilic infiltrate, mainly involving the interfoveolar lamina propria. Although the diagnostic threshold for EoG has not been determined, the presence of ≥30 eosinophils per high-power field (hpf) in at least 5 hpfs, or ≥50 eosinophils in at least 1 hpf have been proposed and used in clinical studies. (H&E; original magnification 20×). (D) Granulomatous gastritis. Non-necrotising granuloma within the lamina propria of a gastric mucosal specimen obtained from a patient with Crohn’s disease. Most cases are associated with either Crohn’s disease of sarcoidosis, but in many instances, no association is found and such cases are classified as idiopathic (H&E; original magnification 20×).
One clinical problem concerns the semantics of the "temporal" definition of these diseases, usually classified as acute versus chronic. Most of these conditions are self-limiting and may completely subside either as a consequence of, or independently of medical management. In other cases, the inflammatory lesions persist and may involve other organs. Their uncertain aetiopathogenetic profile prevents specific aetiology-based therapies. However, because of the low prevalence and the minimal or absent risk of cancer progression, the clinical relevance of these entities remains low. A notable exception is represented by EBV, which is involved in a specific subtype of gastric cancer with unique genomic aberrations and significant clinicopathological features.
"H. pylori 음성 위염에는 여러 가지 확인된 위험 요소와 의심되는 위험 요소가 있다."
<Comment>
Chronic active gastritis (ie, mononuclear infiltrate with a variable neutrophil component)를 가진 환자들 중 일부에서는 H. pylori의 현재 혹은 과거 감염에 대하여 special histological stains, immunohistochemistry, PCR 또는 positive serology로 찾을 수 없을 수 있습니다. 이렇게 Helicobacter organisms을 찾을 수 없는 chronic ative gastritis가 있는 몇 가지 가능한 원인들(eg, medications, chemical injuries, other infections, AIG)이 있으나, 특별한 원인을 확인할 수 없는 경우도 있습니다.
Other infections (eg, EBV, cytomegalovirus, Mycobacterium avium intracellulare, herpes simplex virus)나 immunemediated disorders (eg, lymphocytic gastritis, Crohn’s disease and ulcerative colitis)에서 위 점막의 low-grade 또는, focal chronic active inflammation이 관찰될 수 있습니다. 최근에는 Helicobacter-negative chronic gastritis 의 대부분의 원인을 ‘altered gastric microbiome’ (see section 2.7)으로 믿고 있습니다. 하지만, H. pylori-negative gastritis의 gastritis에 대한 문제에 대한 기여도는 매우 낮습니다 (<1% of all chronic active gastritis). 종종 보고되는 Primary gastric mucosa-assisted lymphoid tissue (MALT) lymphomas 외에, 이러한 형태의 gastritis는 epithelial neoplastic lesions으로의 진행과 관련이 없습니다. 다만, Non-H. pylori Helicobacter spp (NHPH)는 돼지, 개, 고양이에서 인간으로 전파되며 유병률은 0.2~6% 정도로 보고 되고 있고, NHPH 감염에 의한 인수공통감염증은 만성 위염, 소화성 궤양 질환, 저등급 MALT 림프종 및 위암과 관련이 있습니다.
"특정 병인의 만성(long-standing)위염은 드물며 일반적으로 위장관의 다른 부위와 관련된 상태의 표현형을 나타낸다. 병인은 전염성 또는 비전염성 물질로 인해 발생할 수 있으며 전신 질환과 관련된 위염과는 다르다."
<Comment>
Rare forms of gastritis는 종종 asymptomatic 또는, dyspeptic symptoms이 있을 수 있지만 내시경 검사에서 우연히 발견됩니다.
The different types of low-prevalence gastritis are summarised in table 2 (section 2.1.2).
Table 2. Aetiology of gastritis
Aetiological assessment 에서는 환자의 병력, 질병의 임상 양상 및 경과, 만성 위염이 위 또는 위외 병리에 국한되는지, 치료에 반응하는지 등 다양한 요인을 비판적으로 고려하는 것이 중요합니다. 이러한 형태의 위염 중 어느 것도 위암 위험 증가와 관련이 없다는 점은 주목할 가치가 있습니다.
"약물은 급성으로 회복되거나 오래 지속되는 병변을 모두 유발할 수 있다. 병인의 원인에 대한 확인은 약 복용의 시간적 연관 관계에 우선하며, 일부 케이스에서는 조직학적 소견이 필요할 수 있다."
<Comment>
The clinical presentation of drug-induced gastritis (DIG) manifestations is highly variable, ranging from an asymptomatic condition to mild dyspepsia and even alarming symptoms (acute and chronic gastrointestinal bleeding, anaemia). Drugs may also cause non-inflammatory mucosal lesions (ie, gastropathy; see table 5 and section 2.1). These lesions, which are not part of the gastritis spectrum, are mentioned here because of their frequent occurrence. They include, among others, oxyntic gland polyps associated with long-term PPI use and lanthanum deposition, resulting from lanthanum carbonate used in the treatment of hyperphosphataemia in patients with chronic renal failure.
* DIG 진단: 약 복용과 임상적, 내시경적, 조직학적 변화가 시기적 연관성을 가지고 있으며, 약을 끊었을 때 사라지거나 현저히 줄어드는 것이 중요함.
(The key to establishing a diagnosis of DIG is the chronological link between drug assumption and the occurrence of clinical, endoscopic and histological changes, as well as the disappearance or a pronounced decrease of those manifestations after drug withdrawal.)
* Endoscopic findings: non-specific, erythema, petechiae, mucosal lesions (erosions and ulcers) - most often seen in the context of NSAID, aspirin, and oral iron or potassium tablets. Immune checkpoint inhibitors may induce diffuse, oedematous, granular mucosal lesions with erosions or ulcers. In the absence of coagulopathy, gastric biopsies are recommended according to the standard updated Sydney System protocol. Histological assessment may provide findings that allow ascribing specific types of drugs to clinical manifestations and gastric mucosal damage (table 5).
* Management of DIG: withdrawal of the drug and the use of acid inhibitors (H2 blockers or PPI). If present, H. pylori eradication is indicated, especially in NSAID or aspirin treatment. Gastritis associated with immune checkpoint inhibitors may require additional steroid therapy and infliximab.
약제를 중단할 수 있다면 Drug-induced gastritis는 진행하지 않습니다. DIG는 gastric atrophy나 preneoplastic 또는, neoplastic changes로의 진행과 연관성이 없습니다. 오히려 흥미로운 것은 low-dose aspirin과 certain NSAIDs가 gastrointestinal neoplasia의 risk를 감소시킨다는 몇몇 연구들이 있다는 것입니다.
Table 5. Characteristic features of DIG (drug-induced gastritis) associated with medications 
"면역 매개 질환을 포함한 일부 전신 장애는 위 점막 손상과 관련될 수 있다."
<Comment>
* Gastric involvement 및 atrophic gastritis 연관성이 있는 several immune-mediated systemic (non-communicable; see tables 1 and 2; section 2.1.2) diseases : lupus erythematous, scleroderma, Sjögren syndrome, IgG4 - related disease
* 종종 무증상이며, chronic gastritis 를 가진 환자에서 내시경 검사 상 우연히 발견되는 경우가 많고, 소화불량증을 호소할 수 있으나 연관된 다른 상태에 따른 증상일 수 있습니다.
* Patients with uraemia: dyspeptic symptoms (more frequent), gastric damage (consists of a haemorrhagic gastropathy)
* Sarcoidosis: rarely affects the gastrointestinal tract (commonly stomach)
* Non-necrotising granulomas may be found, usually without much accompanying inflammation, and patients may present with weight loss and hypoalbuminaemia.
* Gastric mastocytosis (usually associated with mastocytic infiltration of the intestine): commonly abdominal pain & diarrhoea
* Diagnosis: based on clinical course, serology (particularly in immune-mediated systemic diseases), endoscopy and histology
- Autoantibodies may be present in up to 55% of patients with systemic disorders and H. pylori-negative gastritis; the antinuclear antibody is commonly detected.
- Endoscopic features include erythema, oedema, focal petechial haemorrhages, erosions and ulcers.
- Histological features (most common) are summarised in table 6.
(Isolated reports of multifocal low-grade dysplasia in patients with atrophic gastritis associated with autoimmune systemic disease—if confirmed—suggest that this condition may have neoplastic potential.)
Table 6. Histological gastric mucosal findings in systemic diseases
"대부분의 림프상피종 유사 위암은 EBV 감염과 관련이 있는 반면, EBV에 감염된 상피 세포의 클론 성장을 특징으로 하는 선암종은 적게 발생한다. 위의 전암성 병변에 EBV 존재에 대한 강력한 증거는 부족하다."
<Comment>
The aetiological role of EBV in gastric carcinogenesis is not fully understood.
Causal association between the viral infection and a rare type of gastric carcinoma (lymphoepithelioma-like (LEL))
* Global prevalence of EBV positivity among LEL cases: 90%
* EBV-positive gastric cancer is the most common EBV malignancy globally, with ~80000 cases annually.
* EBV-positive gastric cancers는 EBV-negative tumors 와 demographic, clinicopathological, molecular differences를 갖습니다.
* Cancer Genome Atlas를 보면 독특한 분자 패턴(예: DNA 과메틸화, PIK3CA 돌연변이, JAK2, 프로그래밍된 세포 사멸 단백질 리간드 1(PD-L1) 및 PD-L2 증폭)을 통해 EBV 양성 위암과 연관되어 있으며, 이는 Microsatellite instability (돌연변이율이 높음), 주로 이수성을 나타내는 chromosomal instability, p53 돌연변이 및 RTK-RAS 활성화, 또는 주로 RHO 계열 GTPase 활성화 단백질과 관련된 게놈적으로 안정적인 암과 관련된 변종 중 하나입니다.
* EBV-positive cancer prevails in males, is associated with smoking habit and history of gastric surgery, and most frequently displays proximal gastric location. EBV expression in cancer tissue specimens is a favourable prognostic factor.
* EBV-positive gastric cancer features diffuse histological phenotype coexisting with prominent inflammatory infiltrate, and expressing PD-L1. Alterations in specific chemokines and PD-L1 characterise the systemic response to EBV-positive tumours. Thus, patients with EBV-positive gastric cancer may benefit from immunomodulatory therapies. Oxidative stress may play a critical role mediating EBV reactivation from latency.
* The mechanism for EBV epithelial cell entry은 파악하기 어려운 상태이며, 여전히 EBV가 gastric epithelial cells로 들어와서 carcinogenesis를 일으키는 정확한 stage에 대해서도 아직 모릅니다. Recent evidence demonstrates that EBV uses ephrin A2 receptor to enter epithelial cells. By promoting exposure of ephrin A2 receptor, H. pylori ultimately promotes the infection of gastric epithelia.
* H. pylori-driven gastritis attracts EBV-positive B lymphocytes. The cell-to-cell contact between lymphocytes and gastric epithelia initiates the EBV lytic cycle in B cells, promoting viral transmission. Expression of EBV by in situ hybridisation is variable in gastric dysplastic lesions. Studies of atrophic gastritis documenting EBV DNA by PCR based techniques lack information on the localisation of the viral gene products in the gastric tissues and do not provide conclusive results.
<6. Low-prevalence gastritis>
The predominant impact of H. pylori infection has minimised the epidemiological relevance of non-H. pylori gastric inflammatory diseases. The Kyoto international classification details agents potentially involved in inflammatory gastric diseases. These stomach-based inflammatory lesions are distinguished from gastritis due to potential gastric involvement in systemic diseases, which diagnostic and the therapeutic criteria follow those of the causative systemic illness (table 2 and section 2.1.2).
Among the aetiopathogenic agents of inflammation, the WHO International Agency distinguishes communicable (mostly environmental, particularly infectious) from non-communicable (mostly immunomodulated, host-related) agents (table 2 and section 2.1.2). The epidemiological impact of several of these conditions has been difficult to establish and varies according to their diverse definitions, ethnic differences and socioeconomic contexts. Moreover, clinical practice shows that inflammatory gastric lesions without any detectable aetiological agents are common.
A detailed description of the specific phenotypes of low prevalence gastritis is beyond the scope of this consensus. Since diagnostic criteria are not yet established, one should refer to the most updated pertinent literature (가장 최근 update된 참고 문헌). For example, at the time of this writing, no consensus has been reached on the topographic distribution and the numbers of eosinophils or lymphocytes required to make a diagnosis of eosinophilic or lymphocytic gastritis (figure 10). (예를 들어, eosinophilic or lymphocytic gastritis를 진단 하는데 필요한 일정 범위에서의 eosinophils or lymphocytes 수는 아직 consensus가 없음)
Figure 10. Low-prevalence host-related gastritis. A significant number of low-prevalence gastritis is listed among those aetiologically classified as host related. (A) Lymphocytic gastritis in oxyntic mucosa. Intraepithelial small lymphocytes (IELs), immunohistochemically profiled as CD3 positive, infiltrating the superficial epithelium. The usual diagnostic threshold for the number of IELs is 20 IELs per 100 epithelial cells. However, since the normal stomach has essentially no IELs, in clinical practice, a count higher than 10 IELs per 100 epithelial cells can be assumed to represent lymphocytic gastritis. (H&E; original magnification 20×). (B) Collagenous gastritis. A subepithelial collagenous band (≥5 µm in thickness), associated with loss or denudement of the superficial epithelium, is the accepted criterion for the diagnosis of collagenous gastritis. A low-grade mononuclear inflammatory infiltrate, usually in the absence of atrophy, is frequently present (H&E; original magnification 20×). (C) Eosinophilic gastritis (EoG). Antral mucosal specimen featuring a dense eosinophilic infiltrate, mainly involving the interfoveolar lamina propria. Although the diagnostic threshold for EoG has not been determined, the presence of ≥30 eosinophils per high-power field (hpf) in at least 5 hpfs, or ≥50 eosinophils in at least 1 hpf have been proposed and used in clinical studies. (H&E; original magnification 20×). (D) Granulomatous gastritis. Non-necrotising granuloma within the lamina propria of a gastric mucosal specimen obtained from a patient with Crohn’s disease. Most cases are associated with either Crohn’s disease of sarcoidosis, but in many instances, no association is found and such cases are classified as idiopathic (H&E; original magnification 20×).
One clinical problem concerns the semantics of the "temporal" definition of these diseases, usually classified as acute versus chronic. Most of these conditions are self-limiting and may completely subside either as a consequence of, or independently of medical management. In other cases, the inflammatory lesions persist and may involve other organs. Their uncertain aetiopathogenetic profile prevents specific aetiology-based therapies. However, because of the low prevalence and the minimal or absent risk of cancer progression, the clinical relevance of these entities remains low. A notable exception is represented by EBV, which is involved in a specific subtype of gastric cancer with unique genomic aberrations and significant clinicopathological features.
"H. pylori 음성 위염에는 여러 가지 확인된 위험 요소와 의심되는 위험 요소가 있다."
<Comment>
Chronic active gastritis (ie, mononuclear infiltrate with a variable neutrophil component)를 가진 환자들 중 일부에서는 H. pylori의 현재 혹은 과거 감염에 대하여 special histological stains, immunohistochemistry, PCR 또는 positive serology로 찾을 수 없을 수 있습니다. 이렇게 Helicobacter organisms을 찾을 수 없는 chronic ative gastritis가 있는 몇 가지 가능한 원인들(eg, medications, chemical injuries, other infections, AIG)이 있으나, 특별한 원인을 확인할 수 없는 경우도 있습니다.
Other infections (eg, EBV, cytomegalovirus, Mycobacterium avium intracellulare, herpes simplex virus)나 immunemediated disorders (eg, lymphocytic gastritis, Crohn’s disease and ulcerative colitis)에서 위 점막의 low-grade 또는, focal chronic active inflammation이 관찰될 수 있습니다. 최근에는 Helicobacter-negative chronic gastritis 의 대부분의 원인을 ‘altered gastric microbiome’ (see section 2.7)으로 믿고 있습니다. 하지만, H. pylori-negative gastritis의 gastritis에 대한 문제에 대한 기여도는 매우 낮습니다 (<1% of all chronic active gastritis). 종종 보고되는 Primary gastric mucosa-assisted lymphoid tissue (MALT) lymphomas 외에, 이러한 형태의 gastritis는 epithelial neoplastic lesions으로의 진행과 관련이 없습니다. 다만, Non-H. pylori Helicobacter spp (NHPH)는 돼지, 개, 고양이에서 인간으로 전파되며 유병률은 0.2~6% 정도로 보고 되고 있고, NHPH 감염에 의한 인수공통감염증은 만성 위염, 소화성 궤양 질환, 저등급 MALT 림프종 및 위암과 관련이 있습니다.
"특정 병인의 만성(long-standing)위염은 드물며 일반적으로 위장관의 다른 부위와 관련된 상태의 표현형을 나타낸다. 병인은 전염성 또는 비전염성 물질로 인해 발생할 수 있으며 전신 질환과 관련된 위염과는 다르다."
<Comment>
Rare forms of gastritis는 종종 asymptomatic 또는, dyspeptic symptoms이 있을 수 있지만 내시경 검사에서 우연히 발견됩니다.
The different types of low-prevalence gastritis are summarised in table 2 (section 2.1.2).
Table 2. Aetiology of gastritis
Aetiological assessment 에서는 환자의 병력, 질병의 임상 양상 및 경과, 만성 위염이 위 또는 위외 병리에 국한되는지, 치료에 반응하는지 등 다양한 요인을 비판적으로 고려하는 것이 중요합니다. 이러한 형태의 위염 중 어느 것도 위암 위험 증가와 관련이 없다는 점은 주목할 가치가 있습니다.
"약물은 급성으로 회복되거나 오래 지속되는 병변을 모두 유발할 수 있다. 병인의 원인에 대한 확인은 약 복용의 시간적 연관 관계에 우선하며, 일부 케이스에서는 조직학적 소견이 필요할 수 있다."
<Comment>
The clinical presentation of drug-induced gastritis (DIG) manifestations is highly variable, ranging from an asymptomatic condition to mild dyspepsia and even alarming symptoms (acute and chronic gastrointestinal bleeding, anaemia). Drugs may also cause non-inflammatory mucosal lesions (ie, gastropathy; see table 5 and section 2.1). These lesions, which are not part of the gastritis spectrum, are mentioned here because of their frequent occurrence. They include, among others, oxyntic gland polyps associated with long-term PPI use and lanthanum deposition, resulting from lanthanum carbonate used in the treatment of hyperphosphataemia in patients with chronic renal failure.
* DIG 진단: 약 복용과 임상적, 내시경적, 조직학적 변화가 시기적 연관성을 가지고 있으며, 약을 끊었을 때 사라지거나 현저히 줄어드는 것이 중요함.
(The key to establishing a diagnosis of DIG is the chronological link between drug assumption and the occurrence of clinical, endoscopic and histological changes, as well as the disappearance or a pronounced decrease of those manifestations after drug withdrawal.)
* Endoscopic findings: non-specific, erythema, petechiae, mucosal lesions (erosions and ulcers) - most often seen in the context of NSAID, aspirin, and oral iron or potassium tablets. Immune checkpoint inhibitors may induce diffuse, oedematous, granular mucosal lesions with erosions or ulcers. In the absence of coagulopathy, gastric biopsies are recommended according to the standard updated Sydney System protocol. Histological assessment may provide findings that allow ascribing specific types of drugs to clinical manifestations and gastric mucosal damage (table 5).
* Management of DIG: withdrawal of the drug and the use of acid inhibitors (H2 blockers or PPI). If present, H. pylori eradication is indicated, especially in NSAID or aspirin treatment. Gastritis associated with immune checkpoint inhibitors may require additional steroid therapy and infliximab.
약제를 중단할 수 있다면 Drug-induced gastritis는 진행하지 않습니다. DIG는 gastric atrophy나 preneoplastic 또는, neoplastic changes로의 진행과 연관성이 없습니다. 오히려 흥미로운 것은 low-dose aspirin과 certain NSAIDs가 gastrointestinal neoplasia의 risk를 감소시킨다는 몇몇 연구들이 있다는 것입니다.
Table 5. Characteristic features of DIG (drug-induced gastritis) associated with medications
"면역 매개 질환을 포함한 일부 전신 장애는 위 점막 손상과 관련될 수 있다."
<Comment>
* Gastric involvement 및 atrophic gastritis 연관성이 있는 several immune-mediated systemic (non-communicable; see tables 1 and 2; section 2.1.2) diseases : lupus erythematous, scleroderma, Sjögren syndrome, IgG4 - related disease
* 종종 무증상이며, chronic gastritis 를 가진 환자에서 내시경 검사 상 우연히 발견되는 경우가 많고, 소화불량증을 호소할 수 있으나 연관된 다른 상태에 따른 증상일 수 있습니다.
* Patients with uraemia: dyspeptic symptoms (more frequent), gastric damage (consists of a haemorrhagic gastropathy)
* Sarcoidosis: rarely affects the gastrointestinal tract (commonly stomach)
* Non-necrotising granulomas may be found, usually without much accompanying inflammation, and patients may present with weight loss and hypoalbuminaemia.
* Gastric mastocytosis (usually associated with mastocytic infiltration of the intestine): commonly abdominal pain & diarrhoea
* Diagnosis: based on clinical course, serology (particularly in immune-mediated systemic diseases), endoscopy and histology
- Autoantibodies may be present in up to 55% of patients with systemic disorders and H. pylori-negative gastritis; the antinuclear antibody is commonly detected.
- Endoscopic features include erythema, oedema, focal petechial haemorrhages, erosions and ulcers.
- Histological features (most common) are summarised in table 6.
(Isolated reports of multifocal low-grade dysplasia in patients with atrophic gastritis associated with autoimmune systemic disease—if confirmed—suggest that this condition may have neoplastic potential.)
Table 6. Histological gastric mucosal findings in systemic diseases
"대부분의 림프상피종 유사 위암은 EBV 감염과 관련이 있는 반면, EBV에 감염된 상피 세포의 클론 성장을 특징으로 하는 선암종은 적게 발생한다. 위의 전암성 병변에 EBV 존재에 대한 강력한 증거는 부족하다."
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The aetiological role of EBV in gastric carcinogenesis is not fully understood.
Causal association between the viral infection and a rare type of gastric carcinoma (lymphoepithelioma-like (LEL))
* Global prevalence of EBV positivity among LEL cases: 90%
* EBV-positive gastric cancer is the most common EBV malignancy globally, with ~80000 cases annually.
* EBV-positive gastric cancers는 EBV-negative tumors 와 demographic, clinicopathological, molecular differences를 갖습니다.
* Cancer Genome Atlas를 보면 독특한 분자 패턴(예: DNA 과메틸화, PIK3CA 돌연변이, JAK2, 프로그래밍된 세포 사멸 단백질 리간드 1(PD-L1) 및 PD-L2 증폭)을 통해 EBV 양성 위암과 연관되어 있으며, 이는 Microsatellite instability (돌연변이율이 높음), 주로 이수성을 나타내는 chromosomal instability, p53 돌연변이 및 RTK-RAS 활성화, 또는 주로 RHO 계열 GTPase 활성화 단백질과 관련된 게놈적으로 안정적인 암과 관련된 변종 중 하나입니다.
* EBV-positive cancer prevails in males, is associated with smoking habit and history of gastric surgery, and most frequently displays proximal gastric location. EBV expression in cancer tissue specimens is a favourable prognostic factor.
* EBV-positive gastric cancer features diffuse histological phenotype coexisting with prominent inflammatory infiltrate, and expressing PD-L1. Alterations in specific chemokines and PD-L1 characterise the systemic response to EBV-positive tumours. Thus, patients with EBV-positive gastric cancer may benefit from immunomodulatory therapies. Oxidative stress may play a critical role mediating EBV reactivation from latency.
* The mechanism for EBV epithelial cell entry은 파악하기 어려운 상태이며, 여전히 EBV가 gastric epithelial cells로 들어와서 carcinogenesis를 일으키는 정확한 stage에 대해서도 아직 모릅니다. Recent evidence demonstrates that EBV uses ephrin A2 receptor to enter epithelial cells. By promoting exposure of ephrin A2 receptor, H. pylori ultimately promotes the infection of gastric epithelia.
* H. pylori-driven gastritis attracts EBV-positive B lymphocytes. The cell-to-cell contact between lymphocytes and gastric epithelia initiates the EBV lytic cycle in B cells, promoting viral transmission. Expression of EBV by in situ hybridisation is variable in gastric dysplastic lesions. Studies of atrophic gastritis documenting EBV DNA by PCR based techniques lack information on the localisation of the viral gene products in the gastric tissues and do not provide conclusive results.