γH2AX can be a biomarker to distinguish between benign and malignant lesions in bile duct biopsy specimens

Abstract

Introduction: The aim of this study was to determine whether γH2AX, a sensitive marker of DNA double-strand breaks, can be a biomarker to distinguish between benign and malignant lesions in bile duct biopsy specimens. Method: We examined biopsy specimens of 6 bile duct cancer tissues and 12 noncancerous bile duct tissues (inflammatory tissues, n = 7; normal tissues, n = 5). The diagnoses of these samples were confirmed by postoperative histological examination or clinical follow-up. Immunohistochemical examination of γH2AX, p53, and Ki67 was performed for each specimen. The nuclear staining pattern of γH2AX was classified into two categories: a focal staining pattern, characterized by focus formation in the nucleus, and a diffuse staining pattern, characterized by peripheral-nuclear or pan-nuclear staining. The labeling index (LI) of γH2AX-positive cells with the focal staining pattern, γH2AX-positive cells with the diffuse staining pattern, p53-positive cells, and Ki67-positive cells was calculated. Continuous variables were compared using the Mann-Whitney U test. Result: The LI of the γH2AX focal staining pattern was significantly higher in cancerous tissues than in noncancerous tissues (P < 0.01), while there was no significant difference in the LI of the γH2AX diffuse staining pattern, p53, and Ki67 between cancerous and noncancerous tissues (P = 0.62, 0.17, and 0.29, respectively). In cancerous tissues, the LI of the γH2AX focal staining pattern positively correlated with that of p53 (R = 0.65) but not with that of the γH2AX diffuse staining pattern and Ki67 (R = -0.41 and 0.48, respectively). In cancerous tissues, the LI of the γH2AX diffuse staining pattern had no correlation with that of p53 or Ki67 (R = 0.31 and 0.35, respectively). Conclusion: The LI of γH2AX-positive cells with a focal staining might be a useful biomarker to discriminate between benign and malignant lesions in bile duct biopsy specimens.