Micro‐anatomical variation in cellular proliferation in endometrial adenocarcinoma,and inverse correlation between Ki67 and cytokeratin 7 expression

Stewart C J R, Crook M L & Doherty D A
(2010) Histopathology 57, 46–54
Micro‐anatomical variation in cellular proliferation in endometrial adenocarcinoma, and inverse correlation between Ki67 and cytokeratin 7 expression Aims: To investigate micro‐anatomical variations in proliferative activity within uterine endometrioid adenocarcinoma with particular emphasis on tumour areas comprising microcystic, elongated and fragmented (‘MELF’) glands. Methods and results: Ki67 immunoreactivity was assessed in 29 low‐grade endometrial adenocarcinomas specifically comparing conventional tumour glands and areas exhibiting MELF‐type alteration. Furthermore, since Ki67 expression differed between the peripheral and central aspects of larger neoplastic glands, these micro‐anatomical compartments were assessed separately using a semiquantitative scoring system. Most MELF‐type tumour elements were negative for Ki67 or showed only rare (<5% cells) positivity. In contrast, peripheral conventional tumour glands showed prominent Ki67 labelling, but this was significantly reduced in central glandular areas. An inverse correlation between Ki67 and cytokeratin (CK) 7 expression was noted in many tumours. Conclusions: Endometrial adenocarcinomas show micro‐anatomical variations in Ki67 expression and this is often inversely correlated with CK7 immunoreactivity. MELF‐type tumour elements show minimal proliferative activity, a finding that initially appears unexpected for areas of purported active invasion. However, an inverse correlation between cell division and local invasion has been demonstrated in other malignancies, notably during epithelial–mesenchymal transition, and this may reflect a reversible alteration in cellular activity during neoplastic progression.     

Decreased gastric proliferation of foveolar epithelial cells after the eradication of Helicobacter pylori.

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.     

Histological features do not define NSAID-induced gastritis

Nonsteroidal anti-inflammatory drug (NSAID) use is a common cause of peptic ulcer. This study investigated the nature, frequency, and topographic distribution of histological abnormalities of the gastric mucosa associated with chronic NSAID use. A set of 3 to 11 mapped gastric biopsy specimens were obtained from 108 chronic users of NSAIDs and 61 controls. Each specimen was graded from 0 to 3 for each of the following features: foveolar hyperplasia, smooth muscle fibers, edema, neutrophils, intestinal metaplasia, eosinophils, mononuclear cells, mucosal hemorrhage, atrophy, and Helicobacter pylori. We found that foveolar hyperplasia, considered one of the characteristic features of chemical gastropathy, was absent in 66% of NSAID users. Foveolar hyperplasia was present in 37 NSAID users (34%) and in 10 controls (18%); prominent smooth muscle fibers were found in 51 NSAID users (47%) and 10 of the controls (16%). Concurrent H pylori gastritis obscured the histopathologic changes of NSAID use. All other parameters, including H pylori infection rate (57% v 51%) were similar in NSAID users and controls. We conclude that the histological features characteristic of NSAID users were present only in a subset of patients. No single histological feature can be used to characterize or diagnose chemical gastropathy and no simple set of diagnostic criteria can be applied for this purpose.     

Homeostatic mass control in gastric non-neoplastic epithelia under infection of Helicobacter pylori: an immunohistochemical analysis of cell growth, stem cells and programmed cell death

We evaluated homeostatic mass control in non-neoplastic gastric epithelia under Helicobacter pylori (HP) infection in the macroscopically normal-appearing mucosa resected from the stomach with gastric cancer, immunohistochemically analyzing the proliferation, kinetics of stem cells and programmed cell death occurring in them. Ki67 antigen-positive proliferating cells were found dominantly in the elongated neck portion, sparsely in the fundic areas and sporadically in the stroma with chronic infiltrates. CD117 could monitor the kinetics of gastric stem cells and showed its expression in two stages of gastric epithelial differentiation, namely, in transient cells from the gastric epithelial stem cells to the foveolar and glandular cells in the neck portion and in what are apparently progenitor cells from the gastric stem cells in the stroma among the infiltrates. Most of the nuclei were positive for ssDNA in the almost normal mucosa, suggesting DNA damage. Cleaved caspase-3-positive foveolar cells were noted under the surface, suggesting the suppression of apoptosis in the surface foveolar cells. Besides such apoptosis of the foveolar cells, in the severely inflamed mucosa apoptotic cells were found in the neck portion where most of the cells were Ki67 antigen-positive proliferating cells. Beclin-1 was recognized in the cytoplasm and in a few nuclei of the fundic glandular cells, suggesting their autophagic cell death and mutated beclin-1 in the nuclei. Taken together, the direct and indirect effects of HP infection on the gastric epithelial proliferation, differentiation and programmed cell death suggested the in-situ occurrence of gastric cancer under HP infection.     

Gastric histologic findings in patients with nonsteroidal anti-inflammatory drug-associated gastric ulcer.

The purpose of this study was to characterize gastric histologic findings in patients with nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcer (GU). Gastric biopsy specimens from 136 patients with NSAID-related GU were compared with those from a control population of 185 patients with Helicobacter pylori-related gastritis. Foveolar hyperplasia, edema, muscular stranding, vascular ectasia, and active and chronic inflammation were semiquantitatively graded. Lymphoid aggregates, intestinal metaplasia, atrophy, and cystic gland changes were noted. No single parameter reliably distinguished between the two populations, although moderate/severe foveolar hyperplasia, edema, and vascular ectasia were significantly more common in the NSAID group. With use of the Dixon scoring system for reflux/reactive gastropathy, with a threshold score of 11 or more, 39 (29%) patients in the NSAID group were correctly diagnosed as having reactive gastropathy (sensitivity, 29%; specificity, 100%; positive predictive value, 100%). When the Dixon scoring threshold score was decreased to 8 or more, 114 (84%) patients were classified as having reactive gastropathy (sensitivity, 84%; specificity, > 99%; positive predictive value, > 99%). We conclude that a decreased threshold enhances the usefulness of the reactive gastropathy score in the NSAID-related GU population. Additional studies, however, must be performed to evaluate the effect of a lowered threshold relative to a normal population and those with other causes of reactive gastropathy.     

Helicobacter pylori infection and erosive gastritis

One hundred and eleven patients were included in the study. Thirty seven had erosive gastritis, thirty four chronic gastritis and forty were controls without any gastrointestinal diseases confirmed by symptoms and upper gastrointestinal endoscopy. Patients with erosive gastritis were divided into non-steroidal anti-inflammatory drug (NSAID) users and non-users. H pylori status was determined by urease test, serology and/or histology. The prevalence of H pylori was compared between the various groups. The prevalence of H pylori infection in erosive gastritis, chronic gastritis and controls was 68%, 76% and 65%, respectively, the difference was not significant (P > 0.05), 8 out of 11 patients with erosive gastritis and NSAID use (73%) were positive for H pylori. Likewise 17/26 patients with erosive gastritis without NSAID use (65%) were positive for H pylori (P > 0.05). Body of the stomach (65%) was the commonest site for erosions compared to antrum (43%) or fundus (27%) (P < 0.02). H pylori infection does not predispose to erosive gastritis. NSAID use does not affect H pylori prevalence. Routine H pylori eradication is, therefore, not indicated in patients with erosive gastritis infection. Body of the stomach is the most predominant site for erosions.     

Immunohistochemical profile of normal mesothelium and histiocytic/methothelial hyperplasia: a case report

Immunohistochemical profiles of normal mesothelium and histiocytic/mesothelial hyperplasia (HMH) are unknown. A 19-year-old man was treated by thoracoscopic resection of bullae of left lung. Histologically, there were cell proliferative foci composed of round cells without significant atypia (histiocyte, mesothelium and T-lymphocytes). The cell proliferative foci were patch-like, and no invasive features were seen. Because it is composed of histiocytes, mesothelium, and T-lymphocytes, the diagnosis was HMH. Immunohistochemically, cell components of HMH showed the following immunoreactions: calrenitin 3+, D2-40 3+, pancytokeratin AE1/3 3+, pancytokeratin CAM5.2 3+, cytokeratin (CK) 34βE12 1+, CK5/6 1+, CK7 1+, CK8 3+, CK 14 1+, CK18 2+, CK19 2+, p53 10%, Ki67 20%, CD68 3+, CD45 2+, CD45 RO 2+, vimentin 3+, Ber-EP4 -, CK20 -, EMA -, desmin -, CEA -, CA19-9 -, TTF-1 -, S100 protein -, αsmooth muscle actin -, CD34 -, CD20 -, chromogranin -, synaptophysin -, NSE -, CDX2 -, CD56 -, HER2 -, MUC1 -, MUC2 -, MUC5AC -, and MUC6 -. The normal mesothelium showed the following immunoprofile: calrenitin 3+, D2-40 3+, pancytokeratin AE1/3 3+, pancytokeratin CAM5.2 3+, CK34βE12 3+, CK5/6 2+, CK7 2+, CK8 3+, CK 14 -, CK18 3+, CK19 2+, vimentin 1+, p53 -, Ki67 1%, CD68 -, CD45 -, CD45 RO -, Ber-EP4 -, CK20 -, EMA -, desmin -, CEA -, CA19-9 -, TTF-1 -, S100 protein -, α-smooth muscle actin -, CD34 -, chromogranin -, synaptophysin -, NSE -, CDX2 -, CD56 -, HER2 -, MUC1 -, MUC2 -, MUC5AC -, and MUC6 -. These findings indicate that the immunoprolfile of mesothelium in HMH was immunohistochemically very similar to that of normal mesothelium except for CD68, p53 protein, Ki-67 labeling, CD45 and CD45 RO. These indicate that the HMH was reactive phenomenon and HMH is composed of hyperplastic mesothelium, histiocytes and T-lymphocytes. The immunoprofile of normal mesothelium provide basic knowledge of mesothelial pathology.     

Gastric reddish streaks in the intact stomach: Endoscopic feature of reactive gastropathy

The pathogenesis of reddish streaks in the intact stomach is unclear. Sixty‐three functional dyspeptic patients with gastric reddish streaks were recruited for the study. Fifty‐five patients (group I) had only reddish streaks while nine patients (group II) had additional lesions such as reddish patches or spots randomly scattered throughout the stomach. Updated Sydney system and parameters of reactive gastropathy were used to score the biopsy specimens from reddish streaks separately. Helicobacter pylori infection rate was found to be markedly lower in group I than group II patients (13% vs 89%, P < 0.001). H. pylori‐infected patients had higher scores for acute and chronic inflammation (P < 0.001) and foveolar hyperplasia (P < 0.005) than non‐infected patients, while other parameters for gastritis and gastropathy were similar between infected and non‐infected patients. In H. pylori‐non‐infected patients all biopsy specimens had at least one histological feature of reactive gastropathy. Bile reflux was observed in 54% of patients (34/63). Only 7.9% used non‐steroidal anti‐inflammatory drugs and 4.9% drank alcohol. The present data indicate that the fundamental histological features of gastric reddish streaks are reactive gastropathy with low H. pylori infection, and are probably enterogastric reflux related in etiology. Coincidental H. pylori infection increased acute and chronic inflammatory cell infiltration, and enhanced the grade of foveolar hyperplasia.     

Acute inflammation of the proliferative zone of gastric mucosa in Helicobacter pylori gastritis.

The neutrophilic infiltration has been regarded to represent the activity of Helicobacter pylori gastritis. It may involve the epithelium and/or lamina propria. The incidence and degree of the two types of infiltration do not correlate with each other frequently. We correlated the two types of neutrophilic infiltration with H. pylori infection and other pathologic parameters respectively in 300 randomly selected gastric biopsies as well as serial biopsies from a separate group of 95 patients who were treated for H. pylori infection. The "random biopsies" had chronic gastritis of various degrees, and the organisms were identified in 239 cases (79.7%); in the "treated group," the organisms disappeared completely in 62 cases (65.3%). Characteristically, the intraepithelial neutrophilic infiltration was predominantly localized to the proliferative zone of the gastric mucosa (zone 2) where the density of H. pylori was considerably lower than the surface epithelium. In the "random biopsies," both acute epithelial and interstitial neutrophilic infiltration correlated significantly (p < 0.01) with the H. pylori infection. In the "treated group," however, only acute epithelial inflammation correlated significantly (p < 0.01) with the eradication of infection while acute interstitial inflammation did not. Acute epithelial inflammation was no less frequently present in advanced chronic gastritis than in early chronic gastritis. Acute epithelial inflammation of the proliferative zone is a characteristic pathologic finding of H. pylori gastritis, and appears to be directly associated with the pathogenesis of H. pylori gastritis and its progression.     

Epithelial cell markers and proliferating cells in odontogenic jaw cysts

The expression of keratins, CEA, EMA, and rat liver antigen (RLA) and the presence of Ki67+ proliferating cells were studied in the epithelial linings of 50 odontogenic cysts using an indirect immunoperoxidase method on acetone-fixed frozen sections. All cysts were positive with monoclonal antibodies of broad keratin specificity (CK1, AE1-3), and between 40 and 100 per cent of epithelial cells expressed keratins 13 and 19. Keratins 7, 8, and 18 were rarely expressed although surface cells in areas of mucous metaplasia often expressed keratins 7 and 18. Expression of keratin 10/11 was related to the presence of a well-ordered epithelial lining and was detected in isolated cells in 4/32 non-keratinizing cysts and in the upper suprabasal cell layers of 17/18 keratocysts. Although CEA, EMA, and RLA were detected in the epithelium of all specimens, the pattern of expression of CEA and EMA differed between cyst types. Ki67+ proliferating cells were most prevalent in keratocyst epithelia, where they were usually found within lower suprabasal layers which were negative or weakly positive for keratins 10/11 and 13. These results indicate differences in keratin, CEA, and EMA expression between cyst types which appear to be dependent on epithelial differentiation/structure rather than cyst type or histogenesis. Although these differences may not be of diagnostic significance, the consistent expression of both keratins 13 and 19 may provide a useful marker of odontogenic epithelium in general.     

Association of Helicobacter pylori with HLA-DR antigen expression in gastritis.

AIMS: To assess the association between Helicobacter pylori-associated gastritis and HLA-DR antigen (class II antigen) expression. METHODS: Fifty endoscopic gastric biopsy specimens were studied for the presence of H pylori, degree and type of inflammation, and for HLA-DR antigen expression in the epithelium. The cases were chosen to represent different categories: inflamed gastric mucosa with (n = 13) and without (n = 20) H pylori, and non-inflamed mucosa (n = 17). RESULTS: The antigen was aberrantly expressed in the antral mucosal epithelium in 11 of 12 cases (92%) with acute-on-chronic gastritis when H pylori was also present. It was present in the antrum in only seven of 18 H pylori negative cases (39%) with acute-on-chronic/chronic gastritis. One of three cases of acute gastritis and three of seven cases of chronic gastric erosions (non-inflamed category) showed positive staining. Generally, there was more staining in the antral than body mucosa and in the surface/foveolar epithelium than in the glands. No aberrant HLA-DR antigen expression was found in the 10 cases of normal gastric mucosa examined. CONCLUSIONS: These findings suggest that H pylori may have a role in the induction of class II HLA antigen expression in chronic gastritis and lend support to the view that these organisms may be responsible for part of the inflammatory response.     

"Malgun" (clear) cell change of gastric epithelium in chronic Helicobacter pylori gastritis

To characterize the Helicobacter pylori gastritis-associated epithelial change, we analyzed 251 randomly selected gastric biopsies. The "malgun" (clear) cell change of the gastric epithelium was noted in 229 biopsies (91.2%). Malgun cells were characterized by large, pale nuclei with a euchromatin pattern, enlarged nucleoli, and clear cytoplasm. In the proliferative zone, individual malgun cells and small clusters were often in close contact with infiltrating neutrophils, suggesting that they had developed individually in the background of acute foveolitis. Mitotic figures of malgun cells were not infrequent, including atypical ones. In the surface epithelium, most malgun cells were in clusters that were often large enough to occupy wide epithelial segments. With Warthin-Starry triple staining, they were distinguished by the absence of silver impregnation, while other cells showed staining of the heterochromatin. They displayed prominent immunostaining for low molecular weight cytokeratin (No. 8). Most malgun cells were PCNA-positive in both surface and proliferative zones, whereas Ki67-positive cells were found only in the proliferative zone. It was suggested that a population of malgun cells, which were positive for PCNA only, were in the process of active DNA repair. The malgun cell change may represent a "cellular pattern of activation" in a population which had significant DNA damage, but somehow escaped the detection by the apoptosis system. The notion of "damage at the genetic level" was supported by the observation that these cells remained at least for 8 weeks after eradication of the H. pylori infection.     

The role of apoptosis and proliferation of epitheliocytes in morphogenesis of Helicobacter pylori-associated gastritis

77 patients with chronic Helicobacter gastritis verified endoscopically and exacerbation of duodenal ulcer were examined. H. pylori infection was identified by the rapid ureasa test (CLO-test) and Giemza staining. The patients received 7-day three-component therapy for eradication of H. pylori. Apoptosis and proliferation were studied in 16 patients in serial sections with the use of monoclonal antibodies. Eradication of H. pylori resulted in relief of inflammation and transformation of active gastritis in inactive one. H. pylori-associated gastritis is associated with activation of apoptosis of gastric mucosa epithelial cells and epitheliocytes proliferation. H. pylori eradication alters correlation between apoptosis of epitheliocytes and their proliferation: successful eradication of the infection decreases apoptosis, high proliferative activity of epitheliocytes persists reflecting enhancement of regeneration in gastric mucosa.     

Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis.

We have observed expansions of intraepithelial lymphocytes in duodenal biopsies from patients with Helicobacter pylori gastritis. This study was undertaken to prospectively evaluate, unselected, paired gastric and duodenal biopsies from 50 patients with H. pylori gastritis and a comparison group of 30 patients with other types of gastritis (10 autoimmune and 20 reactive) to: (1) quantify duodenal intraepithelial lymphocytes, determine their distribution patterns, epithelial location, and phenotype, and (2) correlate the intraepithelial lymphocyte elevations with various features of gastric and duodenal pathology. Intraepithelial lymphocytes were analyzed with antibodies including CD3, CD8, and TIA-1. A stain for H. pylori was performed on all gastric and duodenal biopsies. Duodenal intraepithelial lymphocytes from patients with H. pylori gastritis (using CD3) ranged from 3 to 42 lymphocytes/100 epithelial cells (mean 18.5) compared to 3 to 18 lymphocytes/100 epithelial cells (mean 6.6) in the comparison group. Intraepithelial lymphocyte elevations were seen in 44% of the duodenal biopsies from patients with H. pylori gastritis (using CD3). Significant differences in the intraepithelial lymphocyte counts between patients with H. pylori gastritis and the comparison group were seen for all three T-cell antigens (P<0.001 for CD3 and CD8 and P<0.002 for TIA-1). Duodenal intraepithelial lymphocytes in the H. pylori+ cases had a latent cytotoxic phenotype, H. pylori was not visualized in any of the duodenal biopsies from patients with H. pylori gastritis, and no patient had clinical evidence of celiac disease. Our study highlights frequent duodenal intraepithelial lymphocytosis in individuals with H. pylori gastritis and the lymphocyte distribution patterns (and numbers) overlapped with those described for celiac disease patients. H. pylori gastritis must be considered as a possible explanation for duodenal intraepithelial lymphocytosis with normal villous architecture, especially when lymphocytosis is patchy, intraepithelial lymphocytes display a 'latent' cytotoxic phenotype, and the clinical findings and serologic profile does not fit celiac disease.     

不同分型腺性膀胱炎中CK20、Ki67、Ras P21蛋白表达及 临床意义研究

目的 探讨CK20、Ki67、Ras P21蛋白三种肿瘤标志物在正常膀胱组织、不同类型腺性膀胱炎及膀胱腺癌组织中表达的特点。方法 将腺性膀胱炎经典型（泌尿上皮型）20例、肠上皮型20例、前列腺上皮型20例,正常膀胱组织20例、膀胱腺癌组织20例,采用免疫组织化学法,检查CK20、Ki67、Ras P21在各分型腺性膀胱炎中的表达,并与正常膀胱组织、膀胱腺癌组织组进行比较。结果 肠上皮型和前列腺上皮型腺性膀胱炎 CK20、Ki67、Ras P21阳性表达与正常膀胱黏膜组织比较,差异具有统计学意义（P＜0.05）。而经典型（泌尿上皮型）CK20、Ki67、Ras P21的表达与正常膀胱黏膜组织比较,差异无统计学意义（P＞0.05）,肠上皮型和前列腺上皮型腺性膀胱炎及膀胱腺癌中CK20、Ki67、Ras P21高表达。肠上皮型和前列腺上皮型腺性膀胱炎可能为癌前病变。结论 对于肠上皮型及前列腺型腺性膀胱炎,应进行积极的手术治疗及抗癌药物膀胱灌注,并严密术后随访。     

Gastric mucosal inflammation and epithelial cell turnover are associated with gastric cancer in patients with Helicobacter pylori infection

BACKGROUND: Infection with a virulent Helicobacter pylori strain is associated with gastric mucosal damage and the increased risk of gastric cancer. AIMS: To examine the characteristics of host gastric mucosal responses in patients with gastric cancer, histological grade of gastritis, gastric epithelial apoptosis, and proliferation were studied. METHODS: Thirty two patients with early gastric cancer and 32 sex and age matched controls were studied. All subjects were infected with a virulent H pylori strain (vacA s1/m1, cagA positive genotype). Biopsy specimens were taken from the antrum and the corpus of the stomach. The grade of gastritis was assessed according to the updated Sydney system. Apoptotic cells were detected using terminal uridine deoxynucleotidyl nick end labelling, and epithelial cell proliferation was determined by means of the Ki-67 labelling index. RESULTS: In patients with gastric cancer, significantly higher grades were observed when glandular atrophy (p < 0.05) and intestinal metaplasia (p < 0.01) were present in the antrum, and when mononuclear cell infiltration was present in the corpus (p < 0.05). The numbers of apoptotic cells were increased in patients with cancer (p < 0.05) and the apoptotic index correlated significantly with the grade of glandular atrophy. Epithelial cell proliferation was more likely to be increased in mucosa where intestinal metaplasia was present. CONCLUSIONS: Infection with H pylori causes increased gastric epithelial apoptosis, resulting in more severe glandular atrophy in patients with gastric cancer. Increased damage of gastric epithelial DNA and the presence of more severe atrophic gastritis might contribute to the development of gastric cancer.     

Reflux gastritis in gastroesophageal reflux disease: A histopathological study.

Increased intragastric alkaline reflux has been documented in patients with reflux esophagitis; however, the effect on gastric histology has not been investigated in this population. We examined gastric biopsies from 72 non-acid-suppressed patients with gastroesophageal reflux disease (GERD) for changes of reflux gastritis or other forms of gastritis. In the Helicobacter pylori-negative GERD patients (n = 52) using the Dixon scoring system for reflux gastritis with a threshold score of >/=11, reflux gastritis was found in 15% (three of 20) of GERD patients with erosions and in no GERD patients without erosions. When the reflux gastropathy threshold score was changed to more than 8, 90% (18 of 20) of GERD patients with erosions and 19% (six of 32) of GERD patients without erosions were classified as having reflux gastritis. Regardless of the reflux gastritis threshold used, only 14% (seven of 52) of the H pylori-negative GERD patients exhibited normal gastric histology. Inactive chronic gastritis or nonspecific reactive changes were histologic findings in those gastric biopsies not classified as reflux gastritis or normal. All H pylori-positive GERD patients (n = 20) had active chronic gastritis. We conclude that most GERD patients will exhibit some form of gastric pathology: either reflux gastritis, chronic gastritis, or nonspecific reactive changes, depending on what reflux threshold score is applied and the presence of H pylori. Studies to define the intragastric alkaline content in conjunction with gastric histopathology need to be performed to further define those reflux esophagitis patients with reflux gastritis.     

Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection.

Childhood acquisition of Helicobacter pylori is a critical risk factor for gastric cancer. Since tumorigenesis involves deregulation of proliferation and apoptosis, we examined gastric epithelial cell proliferation and apoptosis in H. pylori-infected children. Apoptosis and proliferation of gastric antral epithelial cells in biopsy specimens from patients with H. pylori-induced gastritis, secondary gastritis, and noninflamed controls were compared. p53 protein expression was examined immunohistochemically. Apoptotic cells were identified in the surface epithelium in each group. The apoptotic index was higher in specimens from patients with H. pylori gastritis (120 +/- 10) than secondary gastritis (50 +/- 10) and noninflamed controls (40 +/- 10, analysis of variance P < 0.005). Apoptosis decreased following H. pylori eradication and resolution of gastritis (P < 0.02). An expanded proliferative compartment was identified in H. pylori-induced gastritis (32.4 +/- 3.5; proliferative labeling index +/- SE) compared with secondary gastritis (18.9 +/- 2.8) and noninflamed controls (13.7 +/- 3.1, analysis of variance P < 0.01). The accelerated cell turnover was associated with p53 overexpression (analysis of variance P < 0.005). Accumulation of p53 was not associated with expression of the cyclin-dependent kinase inhibitor p21. The occurrence of altered cell turnover early in the natural history of chronic infection provides an explanation for the increased risk of gastric cancer development associated with childhood acquisition of infection.     

Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration.

AIMS: To evaluate the prevalence and significance of chemical gastritis, in comparison with gastritis related to Helicobacter pylori in patients receiving non-steroidal anti inflammatory drugs (NSAIDs). METHODS: Two hundred and eighteen patients were studied, 174 of whom were taking NSAIDs. Chemical gastritis was defined as the presence of foveolar hyperplasia, muscle fibres in the lamina propria, oedema and vasodilation, in the absence of a chronic inflammatory cell infiltrate. RESULTS: Chemical gastritis was found in 46 (26%) patients taking NSAIDs, and three (7%) in subjects not taking these drugs (p less than 0.01). H pylori was detected in 56 (32%) subjects taking NSAIDs compared with 22 (50%) not taking these agents (p less than 0.02). Ulcers were found in 16 out of 72 patients (22%) taking NSAIDs and without H pylori infection or chemical gastritis compared with 27 out of 56 (48%) with H pylori related gastritis (p less than 0.01), and 25 out of 46 (54%) with chemical gastritis (p less than 0.01). CONCLUSIONS: Peptic ulcers associated with the use of NSAIDs seem to occur more commonly in patients with chemical gastritis or H pylori infection. Patients taking NSAIDs also seem to have a greater prevalence of chemical gastritis but a lower prevalence of H pylori than those not taking these drugs.