Validity of Serum Pepsinogen I/II Ratio for the Diagnosis of Gastric Epithelial Dysplasia and Intestinal Metaplasia during the Follow-Up of Patients at Risk for Intestinal-Type Gastric Adenocarcinoma

Abstract

A cohort of individuals (n = 136) with lesions as severe as atrophic chronic gastritis (ACG) was cross-sectionally evaluated for the validity assessment of pepsinogen I (PGI) and pepsinogen II (PGII) serum levels for the diagnosis of intestinal metaplasia (IM) and gastric dysplasia. PGI/PGII ratio [median (range)] was 4 (0.5-7.5) in patients with ACG (n = 35); 4.6 (1.9-6.8) in type I IM (n = 18); 4.2 (1.4-5.9) in type II or type III IM limited to the antrum and incisura (n = 20); 2.4 (0.4-5.6) in extensive incomplete IM (n = 38); and 1.3 (0.4-6.4) in low-grade dysplasia (n = 23) (P = .002). Using histopathologic data as a reference test, the area under the receiver operating characteristic curves (CI 95%) was 0.73 (0.64-0.82) for extensive IM, 0.72 (0.58-0.85) for the diagnosis of dysplasia, and 0.81 (0.66-0.95) for the diagnosis of high-grade dysplasia. Using a PGI/PGII ratio of < or =3 as the cutoff for dysplasia diagnosis, the sensitivity was 70% (62-78%), the specificity was 65% (57-73%), and the negative predictive value estimates were over 90%. No differences in PG levels according to age or gender were observed. Helicobacter pylori did not significantly influence validity measurement estimates. PGI/PGII serum level ratio can be used even in the management of patients with a high a priori probability for a positive test. It may be useful for the exclusion of more advanced lesions (extensive IM and neoplastic lesions).

Pepsinogen Test for the Evaluation of Precancerous Changes in Gastric Mucosa: a Population-Based Study

“…According to the results of the present population-based follow-up study all high-risk gastric precancerous lesions at follow-up were observed in patients with moderately and strongly decreased PG test at baseline, supporting the opinion that the test could predict atrophic changes (especially if used in combination with H. pylori positivity), demonstrated in some previous studies [3,5,22,23]. However, occurrence of all high-risk gastric mucosa lesions in the groups with a decreased PG level could also be explained by selection bias -response rate might have been higher among those with any previous complaints or changes of PGs at baseline.…”

“…On the other hand, the prevalence of individuals with normal gastric mucosa was high in all groups of patients, even in the group with a severely decreased PG level; 61% of patients were without high-risk lesions, indicating a low specificity of the test. However, the high proportion of false-positive test results could be also explained by other causes that could affect PG levels indicated in other studies [3,5,23,24,25]. Nevertheless, the low specificity of the test should be kept in mind while interpreting patients' data.…”

Serum pepsinogen and gastrin-17 as potential biomarkers for pre-malignant lesions in the gastric corpus

“…The sample size calculation was based upon the equation from power analysis in the diagnostic test. Based upon the study by Dinis-Ribeiro et al (14), the sensitivity and specificity of the serum PGI:II ratio ≤3 in diagnosing extensive IM were 66 and 78%, respectively. Thus, the calculated sample size required to assess the specificity of the serum PGI:II ratio was determined to be 88.…”

“…Cross-tabulation of endoscopy findings and histology results. Histology Non CAG C1 C2 C3 O1 O2 O3 Tumour Total Non CAG 32 2 2 6 1 3 2 0 widely accepted cut-off values for the serum PGI concentration and PGI:II ratio were ≤70 µg/l and ≤3 respectively (14,(37)(38)(39). At these cut-off values, Kitahara et al (37) reported a sensitivity of 84.6% and specificity of 73.5% in gastric cancer screening.…”

“…The PGI:II ratio is greatly reduced in the corpus CAG due to replacement of chief cells by pyloric glands (6,11), while a low G-17 level was observed in H. pylori-infected patients with antral CAG (12,13). Previous studies, however, yielded conflicting results for serum PG (14)(15)(16)(17) and G-17 values as potential biomarkers for CAG (18).…”