Tumor-associated autoantibody signature for the early detection of gastric cancer.

Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150-feature microarray was tested with sera from 100 patients with GC and 100 cancer-free controls, and then the top-ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45-autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.

Long-term dynamics of gastric biomarkers after eradication of Helicobacter pylori infection.

BACKGROUND: Secretion of pepsinogen I (PgI), pepsinogen II (PgII), fasting gastrin-17 (fG-17) and stimulated gastrin-17 (sG-17) changes after Helicobacter pylori eradication. Few data are available on the long-term dynamics of gastric biomarkers after H. pylori eradication.The aim of this study was to investigate the dynamics of gastric biomarkers in H. pylori-positive patients after eradication over a 3-year period and to compare the levels with initially H. pylori-negative patients. MATERIALS AND METHODS: Blood samples for the detection of gastric biomarkers were obtained from dyspeptic patients coming for upper gastrointestinal endoscopy. In H. pylori-positive patients, after eradication therapy, three follow-up blood samples were drawn after 12, 24 and 36 months; in H. pylori-negative patients, two samples were taken - at 12 and after 30 months. Median values of biomarkers in follow-up samples were compared with the baseline sample. RESULTS: The final sample included 110 patients (median age 67 years, M/F ratio 27/83). In patients after H. pylori eradication (n=83) PgI, PgII, fG-17 and sG-17 had decreased significantly during a 36-month period, whereas the PgI/PgII ratio had increased significantly from 5.59 to 11.64. CONCLUSION: In H. pylori-positive dyspeptic patients, after eradication therapy, a decrease in PgI, PgII, fG-17 and sG-17 was observed after 36 months whereas an increase in the PgI/II ratio suggested an improvement in gastric atrophy. The median levels of gastric biomarkers in patients after H. pylori eradication therapy may become similar to biomarker levels among initially H. pylori-negative individuals.

Interobserver variation in assessment of gastric premalignant lesions: higher agreement for intestinal metaplasia than for atrophy.

BACKGROUND: Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. AIMS: The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. METHODS: Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. RESULTS: Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (κ-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. CONCLUSION: The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.