title: Accuracy and cut-off values of pepsinogens I, II and gastrin 17 for diagnosis of gastric fundic atrophy: influence of gastritis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors: Dariush
authors: D
authors: Nasrollahzadeh
authors: Karim
authors: K
authors: Aghcheli
authors: Masoud
authors: M
authors: Sotoudeh
authors: Ramin
authors: R
authors: Shakeri
authors: E Christina
authors: EC
authors: Persson
authors: Farhad
authors: F
authors: Islami
authors: Farin
authors: F
authors: Kamangar
authors: Christian C
authors: CC
authors: Abnet
authors: Paolo
authors: P
authors: Boffetta
authors: Lars
authors: L
authors: Engstrand
authors: Sanford M
authors: SM
authors: Dawsey
authors: Reza
authors: R
authors: Malekzadeh
authors: Weimin
authors: W
authors: Ye
mesh_terms: D000942:Antigens, Bacterial / Q000097:blood; D019540:Area Under Curve; D001426:Bacterial Proteins / Q000097:blood; D005260:Female; D005748:Gastric Fundus / Q000473:pathology*; D005755:Gastrins / Q000097:blood*; D005756:Gastritis / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology; D005757:Gastritis, Atrophic / Q000097:blood* / Q000175:diagnosis* / Q000382:microbiology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood*; D020115:Pepsinogen C / Q000097:blood*; D012016:Reference Values
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005755:Gastrins; C080866:cagA protein, Helicobacter pylori; C013550:gastrin 17; D020115:Pepsinogen C; D020116:Pepsinogen A