Japanese Journal of Clinical Oncology 33:396-398 (2003)
© 2003 Foundation for Promotion of Cancer Research
Morphologic Criteria Using Biopsy Specimens to Define the Risk of Gastric Cancer in Patients with Helicobacter pylori Infection
1 First Department of Internal Medicine, 2 Department of Pathology and 3 Department of Hygiene, Hirosaki University School of Medicine, Hirosaki, Japan
 |
ABSTRACT |
|---|
 TOP ABSTRACT REFERENCES |
|---|
Although Helicobacter pylori (H. pylori) infection is associated with gastric cancer most patients infected with H. pylori do not develop gastric cancer. Gastric biopsy specimens were taken from 49 patients with early intestinal-type gastric cancer and from 49 age- and sex-matched control subjects. Histological features of gastritis were graded according to the updated Sydney System. Mononuclear cell infiltration of the corpus, and intestinal metaplasia of the angle increased the risk of developing gastric cancer. Probability of gastric cancer (PCA) was calculated using these two parameters. The specificities of 70 <PCA for gastric cancer patients, and PCA <30 for non-cancer subjects were 94 and 95%, respectively. PCA <20 was observed only in control subjects. Calculation of PCA, which requires only two biopsy specimens, may be useful to define the patients at high or low risk of intestinal-type gastric cancer among patients infected with H. pylori.
Infection of Helicobacter pylori has been associated with a risk of gastric cancer. A recent prospective study demonstrated that gastric cancer occurred in patients with H. pylori infection, but not in non-infected subjects (1). Most H. pylori-infected subjects, however, do not develop gastric cancer, and chronic gastritis usually remains clinically silent. Therefore, a number of studies have been conducted to identify the risk of gastric cancer among patients with H. pylori infection. This is particularly relevant in Japan because the incidence of gastric cancer is much higher here, than in western countries.
In western countries, corpus-dominant gastritis has been associated with the development of gastric cancer in patients with H. pylori infection (2). Based on this observation, a German group developed the gastric carcinoma risk index. This is a list of histological criteria to define high risk subjects of gastric cancer among patients with H. pylori infection. In our recent study, however, corpus-dominant inflammatory infiltration was frequently observed in both non-cancer control subjects as well as patients with gastric cancer. It precluded the applicability of the gastric carcinoma risk index in Japanese patients infected with H. pylori (3). However, using histological parameters, we recently developed a histological method to calculate the probability of inflammatory bowel disease (4). It will be useful if gastric biopsy specimens are available to calculate the probability for gastric cancer in a similar way. Since most gastric cancers in Japan are of the intestinal type, and H. pylori infection is more clearly associated with the intestinal-type, rather than diffuse-type cancer, focusing on the former would be effective. Therefore, we aimed to establish histological criteria that would enable one to estimate the risk of developing intestinal-type gastric cancer in patients with H. pylori infection. Further, higher rates of histologically detected H. pylori positivity have been reported for early-stage cancer than for advanced cancer. In patients with advanced cancer, the presence of tumors affects H. pylori colonization and inflammatory infiltration of the gastric mucosa. Thus, in the present study, we defined that only intestinal-type cancer in the early stage is eligible as a case.
Patients with early gastric cancer were assembled at Hirosaki University Hospital. A complete histological diagnosis of the tumor type and stage was undertaken on the resected specimens. Gastric cancer was classified as intestinal-type or diffuse-type according to Lauren system, and only patients with intestinal-type cancer were enrolled into the study. We excluded patients with advanced cancer because in their case the prevalence of H. pylori is usually low, and the degree of inflammatory infiltration in the stomach could be affected. Early gastric cancer was pathologically diagnosed by the growth of the tumor confined to the mucosa and submucosa. All cases of cancer were, therefore, Stage 0 or IA [Tis or T1 N0 M0] according to TMN classification. One age- (±3 years) and sex-matched control subject for each cancer patient was randomly and prospectively collected from the subjects who underwent screening for gastric cancer by means of an upper gastro-intestinal endoscopy. Subjects were considered to be eligible for inclusion as controls when their endoscopic diagnosis was normal or only revealed atrophic gastritis. Patients and control subjects were excluded if they had received anti-ulcer agents or antibiotics 2 months before the endoscopy, or had a history of gastric tumors, gastric or duodenal ulcers, or gastric surgery. Of the 72 patients with gastric cancer, 55 had intestinal-type and 17 patients had diffuse-type cancer. Three patients with intestinal-type cancer were excluded because the cancers were in the advanced stage, and three patients without H. pylori infection were also excluded. Finally, the study included 49 patients with early intestinal-type gastric cancer (mean age = 62.1, 35 males and 14 females), and 49 age- and sex-matched control subjects (mean age = 62.0). All cancer patients and control subjects provided informed consent before the endoscopy, and this study was approved by the Ethics Committee of the Hirosaki University.
In cancer patients and controls, three biopsy specimens were obtained for histological examination; one from the greater curvature of the antrum, one from the lesser curvature of the angle, and one from the greater curvature of the middle portion of the corpus. When the tumors were close to the above-mentioned sites, biopsy specimens were taken at least 2 cm away from the tumors. The specimens were embedded in paraffin, and stained with hematoxylin and eosin, and modified Giemsa stain. Histological features of gastritis were graded according to the updated Sydney System (5) by an experienced pathologist (MT). Mononuclear cell (MNC) infiltration, glandular atrophy, and intestinal metaplasia were independent variables; coding normal (= 0), mild (= 1), moderate (= 2), and marked (= 3) at the three biopsy sites. Polymorphonuclear cell (PMN) infiltration was an independent variable; coding present (= 1) or absent (= 0) at any of three biopsy sites. The odds ratio (OR) of these parameters for developing gastric cancer was calculated using a conditional logistic regression analysis. In conjunction with our previous observation, a higher grade of MNC infiltration of the corpus (CIB), and intestinal metaplasia of the angle (IMA) were associated with a higher risk of developing intestinal-type gastric cancer (6). Thus, these parameters were used to calculate the index, that indicates the risk of gastric cancer (PCA) using the following formula:
logitPCA = –2.0362 + 0.8206xCIB + 0.5279xIMA,
PCA = 100xexp (logitPCA) / {1 + exp (logitPCA)}
Intestinal metaplasia of the angle was observed in 78% of the patients with gastric cancer (36 patients were grade 2 or 3), but in only 49% of the control subjects (18 subjects were grade 2 or 3). MNC infiltration of the corpus with grade 2 or 3 was observed in 92% of patients with gastric cancer, while it was observed in 65% of control subjects. Sensitivities and specificities of the PCA values were examined (Table 1). PCA >70 was observed in 16 patients with intestinal-type early gastric cancer, but it was observed in only three control subjects. In contrast, PCA <30 was observed in only two patients, while it was observed in 16 control subjects. The specificities of PCA >70 for gastric cancer patients, and PCA <30 for control subjects, were 94 and 95 %, respectively. Further, PCA <20 was not observed in patients with gastric cancer but was observed in seven control subjects. To confirm the present results PCA was calculated in 28 surgically resected stomachs of patients with early intestinal-type cancer. Biopsy specimens were obtained from 33 subjects who were endoscopically diagnosed as normal or with atrophic gastritis. In 28 resected stomachs of patients with gastric cancer, PCA >70 in 18 patients, and PCA <30 was not observed. On the other hand, among 33 subjects with a normal stomach or atrophic gastritis, PCA >80 was not observed, PCA >70 was observed in only two subjects, and PCA <30 was observed in 11 subjects. These results indicate that PCA is similarly calculated in the different series of patients.
|
In conclusion, MNC infiltration in the corpus, and intestinal metaplasia in the angle are associated with the risk of gastric cancer. Although these histological features are associated with an increased risk of gastric cancer, few studies have associated the grades of these histological features to the risk of gastric cancer. We established the histological criteria using these parameters to define the patients who are at a low or high risk of developing intestinal-type gastric cancer among patients infected with H. pylori. The calculation of PCA requires only two biopsy specimens, and may be useful to predict the clinical outcome of patients infected with H. pylori. However, further prospective studies are necessary to elucidate whether eradication of H. pylori exclusively in patients with 70 <PCA results in a cost-effective prevention of gastric cancer.
|
FOOTNOTES |
|---|
+ For all reprints and correspondence: Tadashi Shimoyama, First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Email: tsimo-hki{at}umin.ac.jp
|
REFERENCES |
|---|
|
TOPABSTRACTREFERENCES |
|---|
1 Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784–9.
2 Miehlke S, Yu J, Schuppler M, Frings C, Kirsch C, Negraszus N, et al. Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease. Am J Gastroenterol 2001;96:1008–13.[CrossRef][Medline]
3 Shimoyama T, Fukuda S, Tanaka M, Nakaji S, Munakata A. Evaluation of applicability of gastric carcinoma risk index for the intestinal type cancer in Japanese patients infected with Helicobacter pylori. Virchows Arch 2000;436:585–7.[CrossRef][Medline]
4 Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H. Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn’s disease from ulcerative colitis. Scand J Gastroenterol 1999;34:55–67.[CrossRef][Web of Science][Medline]
5 Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. Am J Surg Pathol 1996;20:1161–81.[CrossRef][Web of Science][Medline]
6 Fukuda S, Tanaka M, Soma Y, Shimoyama T, Mikami T, Crabtree JE, et al. Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study. J Gastroenterol Hepatol 2000;15:1370–6.[Medline]
Received October 31, 2002; accepted July 25, 2003
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||