Gastric-and-Intestinal Mixed Intestinal Metaplasia Is Irreversible Point with Eradication of Helicobacter pylori

Helicobacter pylori (H. pylori) represents an important factor in the development of atrophic gastritis, intestinal metaplasia (IM), and gastric cancer. Eradication of H. pylori has been reported to prevent gastric cancer only in cases without atrophy or IM. However, histological changes with eradication have yet to be fully clarified. We evaluated 38 H. pylori-positive cases before and after eradication at the gland level;pyloric glands were classified as showing gastric proper (G) and IM gland types, with the latter including gastric-and-intestinal mixed IM (GI-IM) and solely intestinal IM (I-IM), depending on the remaining gastric phenotypes. On eradication, acute and chronic inflammation attenuated rapidly and gradually, respectively, whereas levels of MUC5AC and MUC6 expression were not markedly altered. Gland width, size of nuclei and cytoplasm and their ratio in surface foveolar epithelium, the number of Ki-67-positive cells and the length of the proliferating zone in each gland were significantly decreased in G glands after eradication compared with those in GI-IM and I-IM. The number of mitotic phase cells, positive for phosphorylated histone H3 at serine 28, was increased in both types of IM compared to that in G glands in the H. pylori-infected state, but unexpectedly remained unchanged with eradication. These results suggest that GI-IM, as the beginning of IM, could represent a histological irreversible point with eradication and be considered as a “histological point of no return”.

Expression of Osteopontin and caudal-related homeobox gene 2:indications of phenotypes and prognosis in advanced gastric cancer

Objective:To investigate the expression of osteopontin(OPN)and caudal-related homeobox gene 2(CDX2)in advanced gastric cancer,and to correlate them with clinicopathological features.Method:One-hundred and nine patients suffered from gastric cancer recruited.Expression of OPN and CDX2 and other molecular markers were determined using immunohistochemistry method.Results:Total positive rate of OPN expression was 46.79%,and related with depth of cancer invasion and different phenotype(P<0.001),no association with the patient's age,gender,tumor histological type and lymph node metastasis.In different phenotypes of gastric cancers,OPN frequently expressed in CDX2-negative-expressed G and N type(16/109 and 21/109,respectively),and in CDX2-positive-expressed GI and I types expression level were lower.OPN expression reversely correlated with cdx-2 expression(P<0.001).Patients with OPN positive expression had worse 5-year survival,and patients with OPN negative,5-year survival time better(P<0.001).Further analysis revealed patients with OPN-/CDX2+ had better 5-year survival than other three groups including OPN+/CDX2-,OPN-/CDX2-and OPN+/CDX2+.With multivariate analysis for 5-year survival,it suggested that OPN was the most significant predictor of poor prognosis in gastric cancer(P =0.0043),with lymph node metastasis and tumor depth of invasion were also independent indicators(P =0.0359 and P =0.0315,respectively).Conclusion:Osteopontin is a useful prognostic marker in gastric cancer,and combined with CDX2,it may be much more useful for predicting the survival time in advanced gastric cancer patients.Furthermore it also gave us a clue that in gastric cancer,CDX2 may be a transcription factor modulating the expression of osteopontin.