Abstract
Triple-negative breast cancer (TNBC) is extremely aggressive and associated with poor prognosis. There are no known predictive or prognostic markers for TNBC. Inhibition of tumor protein P53 (TP53) has been demonstrated to increase the levels of cluster of differentiation 117 (CD117) in human colorectal cancer cells. However, the function of TP53 in the regulation of CD117 in TNBC has, to the best of our knowledge, not been reported. In the present study, the association between the expression of CD117 protein and TP53 mutations was investigated, and their prognostic value in patients with TNBC was assessed. A total of 58 TNBC and 48 non-TNBC breast cancer tissue samples were assessed for the expression of CD117, p53 and TP53 mutations. The marker of proliferation Ki-67 (MKI67) proliferation index and vascular invasion index (obtained by measuring D2-40 and CD34) was investigated via immunohistochemistry, and mutations in exons 4-8 of TP53 were measured using direct sequencing. Associations between CD117 and p53 levels or TP53 mutations and clinical parameters were statistically evaluated. The rates of CD117 or MKI67 positivity, CD117+/TP53 missense mutation+, TP53 missense mutations or recurrence were significantly higher in patients with TNBC than in patients with non-TNBC. In TNBC tissues, the presence of CD117 was associated with TP53 missense mutations (P=0.031), vascular invasion, recurrence and MKI67. CD117+/TP53 missense mutation+ also associated with vascular invasion, recurrence and MKI67. Under univariate analysis, MKI67, vascular invasion, CD117, CD117+/TP53 missense mutation+ and TP53 missense mutations were associated with the overall survival of patients with TNBC. Multivariate analysis revealed that vascular invasion and CD117+/TP53 missense mutation+ in primary tumors were independent prognostic factors in patients with TNBC. In conclusion, CD117+/TP53 missense mutation+ was associated with MKI67, vascular invasion and tumor recurrence in TNBC. The presence of CD117 and TP53 missense mutations together in the primary tumors was an independent prognostic factor for survival of patients with TNBC.