Background
CD44 cancer stem cell and MDM2 plays major roles in survival signaling in many cancer cells including cholangiocarcinoma. This study aimed to investigate the distribution of clinicopathological characteristics of cholangiocarcinoma related to the combination between expressions of CD44 cancer stem cell and MDM2 protein by using immunohistochemistry in Thai population.
Methods
A total 64 cholangiocarcinoma tissues were enrolled in this study during June 2012-June 2017. The immunohistochemical staining results were evaluated by two independent pathologists, who was blinded to the clinicopathological details of the patients. The assessment of CD44 and MDM2 staining (score) was based on the percentage of positive cells [lack of staining was scored as negative, 1–50% were classified as 1+, >10 and ≤50% as “2+” and >50% as “3+”]. The cases classified as 0 were considered negative, whereas 1+, 2+ and 3+ were established as positive cases. Significant parameters from the univariate analysis were then assessed in the final by using multivariate analysis using Cox proportional hazards regression modeling with step-wise forward selection, p < 0.05 considered as statistically significant.
Results
In total, 64 cholangiocarcinoma cases (78.1% males and 21.9% females), 35.9% intrahepatic type and 64.1% extrahepatic type. The distribution of clinicopathological characteristics of cholangiocarcinoma related to the combination between expressions of CD44 cancer stem cell and MDM2 protein (multivariate analysis) are high histologic grade [p = 0.016, OR = 2.48 (1.26-4.28)],large tumor size [p = 0.042,OR = 2.59 (1.19-3.28)], lymph node metastasis [p = 0.013,OR= 2.91(1.82-4.09)] , distant metastasis [p = 0.001,OR = 3.38(1.59-5.21)] and poor 5 year survival [p = 0.041,OR 1.52 (1.04-2.26)] were all found to be significantly related to a combination of CD44 and MDM2 expression.
Conclusions
CD44 and MDM2 were significant to poor the clinicopathological outcome of cholangiocarcinoma patients.Co-expression of CD44 and MDM2 in cholangiocarcinoma tissue may indicate an unfavorable patient outcome and may serve as a useful practical adjunct to conventional prognostic indicators for cholangiocarcinoma.