Abstract

Objective: Data from prospective studies indicate a positive impact of gastric cancer screening programs on mortality associated with the disease. Unfortunately, endoscopic procedures, widely regarded as uncomfortable, face low patient compliance, thus underscoring the need for reliable biological markers capable of detection of tumor growth in bodily fluids. Furthermore, in light of the emerging patient-friendly, still devoid of histopathological capabilities, capsule endoscopy, gastric fluid may prove valuable for biomarker-assisted cancer diagnosis. We set out to determine whether CA72-4 measurement in gastric fluid may be of benefit for detection of gastric cancer. Design : Open prospective study. Setting: Sample collection was performed at a tertiary referral center for patients with gastroenterological diseases; immunological analysis was performed at the R&D facility of a commercial biotechnology company. Studies were part of an EU-FP6 project (NEMO). Patients: 176 patients referred for endoscopy due to gastrointestinal complaints. Interventions: Gastric juice was aspirated endoscopically according to standard operating procedures, volume and pH were measured immediately and samples stored at -80°C. Outcome measures: Concentration of CA72-4 tumor marker was evaluated by enzyme-linked immunosorbent assay (ELISA). Results: Median CA72-4 levels were about 4-fold higher in cancer patients compared with patients with normal gastric findings, gastric inflammation, intestinal metaplasia or other diseases (p=0.001). Multivariate linear regression analysis revealed that elevated CA72-4 was significantly predicted by gastric carcinoma adjusted for H. pylori status, age, smoking status, PPI dose, and pH of aspirate (R2=0.27, p<0.0001). In this model, diagnosis of gastric carcinoma had by far the greatest influence. At a cut-off level of 100 U/ml, CA72-4 had 75% sensitivity and 89% specificity for detection of gastric cancer. Conclusions: Based on our findings, CA72-4 level assessment in gastric fluid, featuring yet unmatched accuracy of malignant neoplasia detection may prove beneficial for gastric cancer screening.

Highlights

  • Background and aimsDespite continuous decline in incidence rates in both sexes, gastric cancer is still the fourth most common cancer worldwide, with 934,000 newly diagnosed cases per year[1] and a vast annual death toll of more than 800,000, according to WHO 2004 statistics

  • In the present report we show that CA72-4, whose levels had to date been mainly assessed in serum samples[23,24,25,26], has the potential to become a major biomarker in the gastric fluid-based gastric cancer diagnosis

  • CA72-4 concentrations were measured in 176 gastric juice samples, based on sample volume sufficiency, from subjects with normal stomach (N=28), gastric inflammation (N=58), intestinal metaplasia (N=26), gastric carcinoma and no previous therapy (N=8) and patients with miscellaneous diseases (N=56). 108 out of 176 patients were female

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Summary

Introduction

Background and aimsDespite continuous decline in incidence rates in both sexes, gastric cancer is still the fourth most common cancer worldwide, with 934,000 newly diagnosed cases per year[1] and a vast annual death toll of more than 800,000, according to WHO 2004 statistics. Data from recent prospective studies shows reductions in mortality from gastric cancer among participants in screening programs in Japan and Costa Rica[3,4,5] In this regard, endoscopic procedures, of undisputable great diagnostic value, face a lack of patient compliance, for being widely regarded as uncomfortable. To circumvent this obstacle, reliable biological markers, suitable for detection and monitoring of tumor growth in bodily fluids, have long been searched after, in both blood and gastric fluid. This flaw, expressed in low sensitivity and specificity parameters, obviously negates the idea of utilization of such markers in gastric cancer screening practice

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