Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma

Abstract

TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.

Figure 1

Flow diagram of the study cohort.

Figure 2

Immunohistochemical p53 staining in TNBC. Representative images of nuclear p53 expression (A, B, magnification, × 200, × 400, respectively). TNBC = triple-negative breast cancer.

Figure 3

p53 prognostic significance. Kaplan-Meier curves for DFS associated with p53 expression in the whole cohort of triple-negative breast invasive ductal carcinoma patients as well as in different stratified prognostic stage patients according to the AJCC 8th edition. (A) Total TNBC, (B) AJCC prognostic stage II TNBC, (C) AJCC prognostic stage III TNBC. P values were calculated with use of the log-rank test. AJCC = American Joint Committee on Cancer, DFS = disease-free survival, TNBC = triple-negative breast cancer.

Figure 4

p53 prognostic significance. Kaplan-Meier curves for OS associated with p53 expression in the whole cohort of triple-negative breast invasive ductal carcinoma patients as well as in different stratified prognostic stage patients according to the AJCC 8th edition. (A) Total TNBC, (B) AJCC prognostic stage II TNBC, (C) AJCC prognostic stage III TNBC. P values were calculated with use of the log-rank test. AJCC = American Joint Committee on Cancer, TNBC = triple-negative breast cancer.