The Expression of p66Shc Protein in Benign, Premalignant, and Malignant Gastrointestinal Lesions

Abstract

ROS produced from Oxidative stress have long been recognized to be involved in carcinogenesis. p66Shc generates H(2)O(2) by oxidizing cytochrome c, and its expression has been reported to be elevated in several tumors. However, the expression of p66Shc in gastric cancer has not been reported, and its role in colorectal cancer has not been well elucidated. This study investigated p66Shc expression in benign, premalignant, and malignant gastric and colorectal lesions. p66Shc expression in 146 gastric tumors, 136 colorectal tumors, 45 gastric hyperplastic polyps, 33 gastric low-grade intraepithelial neoplasias, 41 gastric high-grade intraepithelial neoplasias, 42 colorectal hyperplastic polyps, 21 colorectal low-grade intraepithelial neoplasias, 38 colorectal high-grade intraepithelial neoplasias, and 30 normal gastric and colorectal tissues was measured by immunohistochemistry. Most normal gastric and colorectal tissues exhibited low or no p66Shc expression (93.4 %), while most gastric and colorectal tumors exhibited moderate to high p66Shc expression (78.1 %-80.9 %). The p66Shc expression in normal gastric and colorectal tissues were significantly lower than that in the low-grade intraepithelial neoplasias (p < 0.05), high-grade intraepithelial neoplasias (p < 0.01), and gastric adenocarcinomas (p < 0.01 or <0.001). No differences in p66Shc expression were observed in gastric and colorectal hyperplastic polyps compared to the normal tissues. No statistically significant differences in p66Shc expression were observed between patients with different disease stages, different tumor grades, and with or without lymph node metastasis in gastric and colorectal cancers. In conclusion, p66Shc may be involved in the carcinogenesis of gastric and colorectal cancers and could be a marker for the diagnosis of gastric and colorectal cancers.