Research Article: Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer

Date Published: February 2, 2017

Publisher: Public Library of Science

Author(s): Kun-Feng Tsai, Jyh-Ming Liou, Mei-Jyh Chen, Chien-Chuan Chen, Sung-Hsin Kuo, I-Rue Lai, Kun-Huei Yeh, Ming-Tsan Lin, Hsiu-Po Wang, Ann-Lii Cheng, Jaw-Town Lin, Chia-Tung Shun, Ming-Shiang Wu, Qingyi Wei.


Whether the characteristics and prognosis of gastric cancer (GC) are different in patients with and without Helicobacter pylori (HP) remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions.

From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG) I <70 ng/dl and PG I/II ratio < 3.0 were defined as atrophic gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients. We found four characteristics of HP negative GC in comparison to HP positive GC: (1) higher proportion of the proximal tumor location (24.0%, P = 0.004), (2) more diffuse histologic type (56.1%, p = 0.008), (3) younger disease onset (58.02 years, p = 0.008) and (4) more stage IV disease (40.6%, p = 0.03). Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035). In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04–1.71, p = 0.019) in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05–2.51,p = 0.026). We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor.

Partial Text

Gastric cancer remains one of the leading causes of death worldwide[1]. Approximately70% of gastric cancer occurred in developing countries such as Eastern Asia[2]. Helicobacter pylori (H. pylori) is an important causal factor of non-cardiac gastric cancer. The attributable fraction of H. pylori for gastric cancer has been estimated to be about 70%[3], which indicates that about 70% of gastric cancer could be prevented through eradication of H. pylori[4–6]. Also, the association of H. pylori eradication with a reduced incidence of gastric cancer was demonstrated in a meta-analysis study[7]. Nevertheless, gastric adenocarcinoma is a heterogeneous disease. About 30% of gastric cancers are not related to H. pylori infection[3]. Demographic feature, life style, high salt with nitrate intake, race and genetic variables contribute to the heterogeneity[8–12]. Epstein–Barr virus infection associated lymphoepithelioma-like carcinoma is another entity which causes about 5% of gastric cancer[13].

In our study, we found four characteristics of HPNGC in comparison to HPPGC, including (1) higher proportion of the proximal tumor location (24.0%, p = 0.004); (2) more diffuse histologic type (56.1%, p = 0.008); (3) younger disease onset (58.02 years, p = 0.008) and (4) more stage IV cancer (40.6%, p = 0.03). The novelty and strength of this study was that we analyzed the impact of H. pylori status on survival using three different definitions of H. pylori infection in patients with atrophic gastritis and negative serology test and histology for H. pylori. We found that negative H. pylori infection was an independent worse prognostic factor of gastric cancer by using the pepsinogen method. The poor prognostic effect of negative H. pylori status was particularly significant in patients with stage I, II and III disease.




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