OncoTargets and Therapy (Sep 2019)

Positive correlation between programmed death ligand-1 and p53 in triple-negative breast cancer

  • Zeng Y,
  • Wang CL,
  • Xian J,
  • Ye Q,
  • Qin X,
  • Tan YW,
  • Cao YD

Journal volume & issue
Vol. Volume 12
pp. 7193 – 7201

Abstract

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Yan Zeng1, Cheng-Long Wang2, Jie Xian1, Qian Ye3, Xue Qin1, Yi-Wen Tan1, You-De Cao1 1Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Pathology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 3Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: You-De CaoDepartment of Pathology, College of Basic Medicine, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86 236 848 5789Email [email protected]: Tumors with high mutation load tend to have a stronger immune response in some tumors. The correlation between expression of programmed death ligand-1 (PD-L1), a biomarker of immune response in tumors, and p53, accepted as the most frequently mutated gene in many cancers, in triple-negative breast cancer (TNBC) has not been fully investigated in cancer patients.Materials and methods: 132 cases of TNBC and 32 cases of non-TNBC paraffin-embedded tissue sections were selected to detect the expression of PD-L1 and p53 by immunohistochemistry, and results were correlated with clinical data and survival outcomes. The staining of PD-L1 in tumor cells (TCs) and tumor-associated immune cells (TAICs) was assessed separately.Results: Strong positive correlations were observed between expression of p53 and PD-L1 both in TCs (r=0.338, P=0.000) and TAICs (r=0.186, P=0.033). The same positive correlation was found in the expression of PD-L1 in TCs and TAICs (r=0.764, P=0.000). Like p53 (P=0.024), positive rate of PD-L1 in TCs was significantly higher in TNBC than in non-TNBC (P=0.02). PD-L1 and p53 in TCs staining were significantly associated with histological grade, tumor size and Ki67 index (P<0.05). PD-L1 in TCs staining was also associated with lymphatic metastasis status (P=0.000). However, PD-L1 in TAICs was only related to histological grade in statistically (P=0.012). Kaplan–Meier survival analysis showed that positive groups of p53, PD-L1 in TCs and TAICs had a worse overall survival and a worse progression-free survival as compared with the negative groups, but marginal significance was found only in overall survival of PD-L1 in TCs and TAICs, and progression-free survival of PD-L1 in TAICs (P=0.074, 0.097, 0.068, respectively).Conclusion: Our findings suggest that positive correlation between p53 and PD-L1 in TNBC and the higher expression rates are closely correlated with some key prognostic factors and worse survival outcomes. These findings would lay the foundation for further study on the relationship of p53 and PD-L1 and the combination of mutated p53 inhibitors and PD-1/PD-L1 antibodies in TNBC.Keywords: p53, programmed death ligand-1, PD-L1, immunohistochemistry, IHC, tumor cells, TCs, tumor-associated immune cells, TAICs, triple-negative breast cancer, TNBC

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