Evidence that loss of sonic hedgehog is an indicator of Helicobater pylori-induced atrophic gastritis progressing to gastric cancer

BACKGROUND: The absence of sonic hedgehog (Shh) correlates with the development of intestinal metaplasia (IM) suggesting the possibility of an association between Shh expression and neoplastic transformation. AIM: To examine Shh expression in the noncancerous mucosa of patients with gastric cancer and compare it to Shh expression in Helicobater pylori-infected and uninfected controls. We also assessed the relationship between the type of IM and Shh expression. METHODS: Fifty-three patients with endoscopic mucosal resection (EMR) for early gastric cancer and 48 sex- and age-matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. The histopathological grading used was the updated Sydney System. IM was categorized by staining with Alcian blue/high iron diamine. Expression of Shh was evaluated by immunostaining. RESULTS: The Shh immunostaining in the corpus lesser curve significantly correlated with the scores of atrophy and IM. Shh staining in the antrum was significantly higher in H. pylori-negative controls than those in H. pylori-positive controls as well as in patients without IM compared to those with IM (p < 0.001). The Shh staining in the corpus lesser curve decreased in H. pylori-negative controls, -positive controls and the cancer group respectively (p = 0.003), and was significantly higher (p = 0.006) in the complete IM group compared to those in the incomplete IM group. CONCLUSIONS: Loss of Shh is an early change that occurs in the mucosa prior to neoplastic transformation. Its loss correlates with the type of IM and may play a role in carcinogenesis.