Accuracy and Cut-Off Values of Pepsinogens I, II and Gastrin 17 for Diagnosis of Gastric Fundic Atrophy: Influence of Gastritis

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
PLoS ONE (Impact Factor: 3.23). 10/2011; 6(10):e26957. DOI: 10.1371/journal.pone.0026957
Source: PubMed


To establish optimal cutoff values for serologic diagnosis of fundic atrophy in a high-risk area for oesophageal squamous cell carcinoma and gastric cancer with high prevalence of Helicobacter pylori (H. pylori) in Northern Iran, we performed an endoscopy-room-based validation study.
We measured serum pepsinogens I (PGI) and II (PGII), gastrin 17 (G-17), and antibodies against whole H. pylori, or cytotoxin-associated gene A (CagA) antigen among 309 consecutive patients in two major endoscopy clinics in northeastern Iran. Updated Sydney System was used as histology gold standard. Areas under curves (AUCs), optimal cutoff and predictive values were calculated for serum biomarkers against the histology.
309 persons were recruited (mean age: 63.5 years old, 59.5% female). 84.5% were H. pylori positive and 77.5% were CagA positive. 21 fundic atrophy and 101 nonatrophic pangastritis were diagnosed. The best cutoff values in fundic atrophy assessment were calculated at PGI<56 µg/l (sensitivity: 61.9%, specificity: 94.8%) and PGI/PGII ratio<5 (sensitivity: 75.0%, specificity: 91.0%). A serum G-17<2.6 pmol/l or G-17>40 pmol/l was 81% sensitive and 73.3% specific for diagnosing fundic atrophy. At cutoff concentration of 11.8 µg/l, PGII showed 84.2% sensitivity and 45.4% specificity to distinguish nonatrophic pangastritis. Exclusion of nonatrophic pangastritis enhanced diagnostic ability of PGI/PGII ratio (from AUC = 0.66 to 0.90) but did not affect AUC of PGI. After restricting study samples to those with PGII<11.8, the sensitivity of using PGI<56 to define fundic atrophy increased to 83.3% (95%CI 51.6-97.9) and its specificity decreased to 88.8% (95%CI 80.8-94.3).
Among endoscopy clinic patients, PGII is a sensitive marker for extension of nonatrophic gastritis toward the corpus. PGI is a stable biomarker in assessment of fundic atrophy and has similar accuracy to PGI/PGII ratio among populations with prevalent nonatrophic pangastritis.

Download full-text


Available from: Reza Malekzadeh
  • Source
    • "Repeated endoscopy would be a good way to evaluate presence or reversal of premalignant lesions, but it is invasive and not without sampling error. Low pepsinogen 1 to 2 ratio (PEP 1:2) has been shown to correlate very well with gastric atrophy [5-8] and is thus an attractive alternative for determining the presence of gastric atrophy. We have previously shown that the prevalence of serologically diagnosed gastric atrophy among patients with normal upper gastrointestinal endoscopies was as high as 28% (26/94) with 23% (6/26) of these being less than 45 years old [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer is a major contributor to cancer deaths in Zambia but, as elsewhere, no preventive strategies have been identified. We set out to investigate the possibility of reducing gastric atrophy, a premalignant lesion, using micronutrient-antioxidant supplementation. We analysed 215 archival samples from a randomised controlled trial of micronutrient-antioxidant supplementation carried out from 2003 to 2006. Participants were randomised to receive either the supplement or placebo and had been taking the allocated intervention for a mean of 18 (range 14-27) months when the samples used in this study were taken. We used low pepsinogen 1 to 2 (PEP1:2) ratio as a surrogate marker of gastric atrophy. A PEP 1:2 ratio of less than three was considered low. HIV serology, age, nutritional status, smoking, alcohol intake and gastric pH were also analysed. Ethical approval was obtained from the University of Zambia Biomedical Research Ethics Committee (011-04-12). The randomized trial was registered (ISRCTN31173864). The overall prevalence of low PEP 1:2 ratio was 15/215 (7%) and it did not differ between the placebo (8/103, 7.8%) and micronutrient groups (7/112, 6.3%; HR 1.24; 95%CI 0.47-3.3; P = 0.79). The presence of low PEP 1:2 ratio was not influenced by HIV infection (HR 1.07; 95%CI 0.37-3.2; P =0.89) or nutritional status but it inversely correlated with gastric pH (Spearman's rho = -0.34; P = 0.0001). Age above 40 years was associated with atrophy, but neither alcohol nor smoking had any influence. Short term micronutrient supplementation does not have any impact on PEP 1:2 ratio, a serological marker of gastric atrophy. PEP 1:2 ratio inversely correlates with gastric pH.
    Full-text · Article · Mar 2014 · BMC Gastroenterology
  • Source
    • "Five-year survival rates have ranged from 90% to less than 5 percent, mainly depending on the stage of diagnosis[5], [6].If gastric cancer can be detected and treated in early stages, the five-year survival rateis better than 90%; however, there isno apparent or specific symptom in early-stage gastric cancer.Thus, early detectionof gastric cancer becomesmore difficult.Although serum pepsinogen (PG) testssuch as low PGI concentration and/or low PGI/II ratio were suggestive screening tests in high-risk countries such as Japan, they weregood indicators of atrophic gastritis rather than diagnostic markersof gastric cancer[7]–[9].Essentially, endoscopy has beenthe promising tool with 2.7 to 4.6-times higher detection rate than barium studies[10]. However,early gastric cancer diagnosis by endoscopydependson professional skill. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer (GC) has a high rate of morbidity and mortality among various cancers worldwide. The development of noninvasive diagnostic methods or technologies for tracking the occurrence of GC is urgent, and searching reliable biomarkers is considered.This study intended to directly discover differential biomarkers from GC tissues by two-dimension-differential gel electrophoresis (2D-DIGE), and further validate protein expression by western blotting (WB) and immunohistochemistry (IHC).Pairs of GC tissues (gastric cancer tissues and the adjacent normal tissues) obtained from surgery was investigated for 2D-DIEG.Five proteins wereconfirmed by WB and IHC, including glucose-regulated protein 78 (GRP78), glutathione s-transferase pi (GSTpi), apolipoprotein AI (ApoAI), alpha-1 antitrypsin (A1AT) and gastrokine-1 (GKN-1). Among the results, GRP78, GSTpi and A1ATwere significantlyup-regulated and down-regulated respectively in gastric cancer patients. Moreover, GRP78 and ApoAI were correlated with A1AT for protein expressions.This study presumes these proteins could be candidates of reliable biomarkers for gastric cancer.
    Full-text · Article · Jan 2014 · PLoS ONE
  • Source
    • "In a recent study , designed in our country , the best cutoff value in gastric atrophy assessment was calculated at PGI, 56 ng/ml (sensitivity: 61.9%, specificity: 94.8%) but we used the cutoff value of PGI <88.7 ng/ml (sensitivity and specificity of 64.4% and 43% respectively) for atrophy (Nasrollahzade et al., 2011). That work was an office based study and 309 persons were enrolled but present study was a population based survey on 1390 persons explaining the difference of cutoff between two studies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. Methods: A cross- sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. Results: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). Conclusions: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.
    Full-text · Article · Jun 2013 · Asian Pacific journal of cancer prevention: APJCP
Show more