Diabetes associated with abnormal p53 immunohistochemical patterns in colorectal cancer

Abstract

Background Previous study has suggested a link between diabetes and colorectal cancer (CRC), but the specific molecule for the link has not been well-understood. Abnormal p53 immunohistochemical (IHC) pattern is an accurate predictor for TP53 gene mutation. The present study aimed to investigate the relationship between type 2 diabetes mellitus (T2DM) and p53 IHC patterns in CRC. Methods We analyzed p53 protein expression of 742 cases of CRC with radical colectomy by immunohistochemistry. The patients were grouped into subsets of non-diabetes (n = 570) and diabetes (n = 172), and further divided into subgroups of 1 normal p53 IHC pattern (p53 wild type or WT) and 3 abnormal p53 IHC patterns which included heterogeneous pattern (HT), overexpression (OE) and complete absence (CA). Results The ratios of p53 abnormal pattern in groups of T2DM and non-T2DM were 70.9% and 50.9% (P < 0.001). Univariately, groups of both T2DM and prediabetes (FPG: 6.1 ~ 6.9 mmol/L) were significantly associated with abnormal p53 pattern, compared with normal FPG control (P < 0.05 and P < 0.001). Moreover, T2DM was significantly associated with abnormal p53 patterns in cases with microsatellite instability (MSI) stable (MSS)/MSI-low phenotype (P < 0.001) and distal colon/rectum location, but not in cases with MSI-high phenotype and proximal colon location (P > 0.05). Multivariate analysis retained the above significance. Furthermore, abnormal p53 IHC patterns were positively associated with risk of lymph node metastasis and high tumor-node-metastasis (TNM) stage of CRC, which suggested a link between the abnormal p53 IHC patterns and aggressive clinical outcome. Conclusion Diabetes is associated with risk of abnormal p53 IHC patterns in CRC. It was suggested that diabetes might influence carcinogenesis, progression and prognosis via inducing TP53 mutation and abnormal p53 expression in CRC.