J Pathol Transl Med.  2019 May;53(3):180-187. 10.4132/jptm.2019.02.08.

Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer

• Lee M
• Park IA
• Heo SH
• Kim YA
• Gong G
• Lee HJ

• KMID: 2449341
• DOI: http://doi.org/10.4132/jptm.2019.02.08

Abstract

BACKGROUND
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
METHODS
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
RESULTS
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
CONCLUSIONS
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.

Keyword

p53; Breast neoplasms; Lymphocytes, Tumor-infiltrating

MeSH Terms

Breast Neoplasms
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Humans
Lymphocytes, Tumor-Infiltrating*
Mutation, Missense
Survival Rate
Triple Negative Breast Neoplasms*

Figure

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  Fig. 1. Distribution of triple-negative breast cancer patients by immunoreactive scores for p53 expression.

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  Fig. 2. Histologic features and p53 expression in triple-negative breast cancer tumors. A tumor with low histologic grade shows sparse tumor-infiltrating lymphocytes (TILs) and low p53 expression (A, D). Tumors with high histologic grade show abundant TILs and no p53 expression (B, E) or high p53 expression (C, F).

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  Fig. 3. Differences in the level of tumor-infiltrating lymphocytes (TILs) (A) and the average number of CD8+ T cells (B) among the three groups of triple-negative breast cancer patients categorized by p53 expression level.

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  Fig. 4. (A, B) Kaplan-Meier survival analyses of triple-negative breast cancer patients categorized by p53 expression levels.

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  Fig. 5. Kaplan-Meier survival analyses of triple-negative breast cancer patients according to tumor-infiltrating lymphocytes levels in low (A, D), no (B, E), and high (C, F) p53 expression groups.

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