Aims
Alpha-fetoprotein-producing colorectal cancer (AFPP-CRC) is quite rarely seen. This study aimed to elucidate the clinicopathologic characteristics and prognostic factors of AFPP-CRC.
Background/aims
Alpha-fetoprotein-producing colorectal cancer (AFPP-CRC) is quite rarely seen. This study aimed to elucidate the clinicopathologic characteristics and prognostic factors of AFPP-CRC.
Conclusion
AFP-positivity is a significant negative predictor of overall survival in patients with colorectal cancer, which may be mediated by HGF/c-Met signaling pathway.
Methods
Among 5,051 colorectal cancer patients receiving surgery in the Fudan University Shanghai Cancer Center from 2006 to 2016, we identified 78 patients with elevated serum level of AFP (> 10 µg/L) preoperatively. A propensity score matching (PSM) analysis was performed which matched 75 AFPP-CRC patients to the same number of AFP-negative colorectal cancer (AFPN-CRC) patients. Kaplan-Meier curves were compared using the log-rank test and multivariable analysis was performed to evaluate the effect of AFP-positivity while adjusting confounding factors. 27 patients were available for immunohistochemical analysis. We conducted functional experiments to characterize the tumorigenicity of AFP.
Results
Patients with AFPP-CRC had a significantly higher incidence of advanced TNM stage and liver metastasis. Overall survival was significantly different between two groups before and after PSM, and AFP-positivity was one of the strongest predictors of overall survival in the multivariable model (HR 4.11, CI 95%: 1.43-11.76, p = 0.009) after PSM. We further investigated prognostic factors affecting prognosis in AFPP-CRC and found that the presence of liver metastasis was the only independent prognostic factor (HR 4.95, CI 95%: 1.48-16.48, p = 0.009). AFP expression was significantly positively correlated with HGF and c-Met expression. Transwell invasion assay revealed significantly increased cell motility with AFP overexpression.