Helicobacter pylori infection‐negative gastric cancer in Japanese hospital patients: Incidence and pathological characteristics

Abstract

We used Helicobacter pylori sero-positivity and mucosal atrophy as detected by the serum pepsinogen method to identify H. pylori infection-negative gastric cancer patients with or without atrophy. One hundred and six of 748 (14.2%) primary gastric cancer patients were infection-negative by a serum antibody detection system. Further, 121 (16.2%) of the 748 were negative for gastric mucosal atrophy by the pepsinogen method, of whom 15/748 (2.0%) were H. pylori-negative by pepsinogen I level (> > > >70 ng/mL) and pepsinogen I/II ratio (> > > >3.0). Twenty-seven of 782 (3.6%) gastric cancer patients were H. pylori-negative by antibodies and severe atrophy as determined by pepsinogen I level (< < < <30 ng/mL) and pepsinogen I/II ratio (< < < <2.0). H. pylori-negative gastric cancer patients with severe atrophy likely had a previous infection. These results indicate that the actual number of H. pylori-negative patients is 2.0% at minimum and 10.6% (14.2% minus 3.6%) at maximum in the general Japanese population. Five of 15 (33%) cases displaying neither anti-H. pylori antibodies nor atrophy were intestinal-type and 10 (67%) were diffuse-type adenocarcinomas. Thirteen surgical patients with primary gastric cancer displaying neither antibodies nor mucosal atrophy were further analyzed for pathological and phenotypic characteristics. The mucin phenotype was divided into four gastric, five gastric and intestinal, two intestinal and two null types, independent of histological classification. Intestinal phenotype elements were detected by Cdx2 immunohistochemical methods in nine of 13 (70%) cases examined. We conclude that a small fraction of gastric cancer patients displayed multifactorial carcinogenesis without H. pylori infection, indicating that gastric cancer risk still exists in the absence of H. pylori infection, at an incidence of 2.0% at minimum and 10.6% at maximum in the general Japanese population. (Cancer Sci 2007; 98: 790-794)T he prevalence of Helicobacter pylori (H. pylori) infection, which varies by ethnicity, location and race, is closely associated with the incidence of gastric cancer. One prospective study found that gastric cancer develops only in patients with H. pylori infection. (1)(2)(3) The gastric mucosa in infected persons is marked by severe atrophic changes associated with intestinal metaplasia. These pathological changes are reported as precursory lesions of gastric cancer, (4) and have raised the possibility of active prevention of the disease. (5,6) However, because H. pylori infection is diminished in severely atrophic mucosa, detection systems for H. pylori infection-negative status have not been fully established. Any conclusive finding of negativity is therefore problematic. Pathological analysis of gastric mucosa after gastrectomy in a series of Japanese patients found that only 2% of gastric cancers occurred in H. pylori-negative patients. (7) Other studies using multiple detection systems including pathological and serological diagnosis similarly found that only 2% of patients with ea...

Negative Helicobacter pylori status is associated with poor prognosis in patients with gastric cancer

“…H. pylori positivity in the general population as well in gastric cancer patients is very high in Japan and in countries with a high incidence of gastric cancer. [19][20][21]29 It is interesting to note that in gastric cancer patients, very low positivity rates of H. pylori infection have been reported from the US, [30][31][32][33] and clinical studies demonstrated clearly lower survival rates when compared with Japanese patients at the same stages of disease. 34 Differences in prognosis between Eastern and Western series have been explained on the basis of different surgical approaches, less advanced stage of disease, and more careful tumor staging 35 ; the association with H. pylori status may shed more light on geographic variability in the prognosis of patients with gastric cancer.…”

“…11,12 However, very high infection rates also have been reported from Japan, and negative H. pylori status in Japanese gastric cancer patients has been recently estimated to range from between 2% and 11%. 20 It is well known that the prevalence of H. pylori infection in the general population is higher in countries with a higher incidence of gastric cancer 21 ; in Tuscany, the incidence of gastric cancer is very high compared with other regions of Italy. 22 Epidemiologic factors and the sensitivity of the methods used could explain the high rates of H. pylori positivity reported in the current series.…”

Biological behavior of the intramucosal Helicobacter pylori-negative undifferentiated-type early gastric cancer: comparison with Helicobacter pylori-positive early gastric cancer

“…In regard to the accuracy of determining HP-status, some studies have referred to the incidence using only histopathology [14] or only anti-HP antibodies and the pepsinogen method [15], one determined it using anti-HP antibodies and histopathology, endoscopic findings, the pepsinogen method, and the urea breath test or the rapid urease test [3], and yet another determined it on the basis of histopathology, the rapid urease test, anti-HP antibodies, and a history of eradication therapy [16]. In contrast, we used six criteria [urea breath test results (negative), endoscopic findings, histopathology, pepsinogen test results, presence of anti-HP antibodies, and history of eradication therapy] in our study to select HP-patients.…”

Serum <i>Helicobacter Pylori</i> IgG Titers are Predictive of <i>H. pylori</i> Infection Status

“…It should be noted that the incidence of gastric cancer in patients seronegative for H. pylori was 2 12 , compared with 0.66 in those without H. pylori infection 13 . This difference is likely due to the inclusion of current or previous H. pylori-infected subjects with negative serological test results.…”