Clinicopathological and epidemiological significance of breast cancer subtype reclassification based on p53 immunohistochemical expression

Abstract

TP53 mutations are common in breast cancer and are typically associated with more aggressive tumor characteristics, but little is known about the clinicopathological and epidemiological relevance of p53 protein expression, a TP53 mutation surrogate, in breast cancer subtypes. In this study of 7226 Chinese women with invasive breast cancer, we defined breast cancer subtypes using immunohistochemical (IHC) measures of hormone receptors and HER2 in conjunction with histologic grade. p53 expression status was then used to further stratify subtypes into p53-positive and p53-negative. Odds ratios (ORs) and 95% confidence intervals (CIs) in case-only logistic regression analyses were used to examine heterogeneity across different subtypes. The frequency of p53 protein expression varied by breast cancer subtype, being lowest in the luminal A-like and highest in the triple-negative and HER2-enriched subtypes ( P -value < 0.01). In luminal A-like and B-like/HER2-negative subtypes, p53 positivity was associated with early-onset tumors, high grade, high proliferative index, and basal marker (CK5/6 and EGFR) expression. Further, compared with luminal A-like/p53-negative patients, A-like/p53-positive patients were more likely to be parous [adjusted OR parous vs. nulliparous = 2.67 (1.60, 4.51); P -value < 0.01] and to have breastfed [adjusted OR ever vs. never = 1.38 (1.03, 1.85); P -value = 0.03]. p53 positivity was not associated with examined clinical and risk factors in other tumor subtypes. Overall, these findings suggest that p53 expression, which is readily available in many settings, can be used to identify phenotypes of luminal A-like breast cancer with distinct clinical and epidemiological implications.

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

“…In our study detected TP53 protein expression by immunohistochemistry reflected the mutant TP53 gene and we found that negative TP53 expression was a favorable prognostic indicator for better overall survival, however, it was not an independent prognostic factor in the multivariate analysis. Similar results have been previously reported [29,3,28].…”

“…This is consistent with other studies that outlined the role of TP53 in the progression of breast carcinoma and indicated a poor prognosis [3,28]. The high frequency of TP53 expression in the TNBC is an independent prognostic factor, which might aid in identifying subgroups of TNBC patients who are more likely to have a poor outcome and to whom specific therapies might be directed [29,3]. In our study detected TP53 protein expression by immunohistochemistry reflected the mutant TP53 gene and we found that negative TP53 expression was a favorable prognostic indicator for better overall survival, however, it was not an independent prognostic factor in the multivariate analysis.…”

Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

“…The UICC TNM System was adopted to classify the clinical stage of the disease at presentation [21]. Evaluation of the Estrogen receptor (ER), Progesterone receptor (PR) and HER2 contents of the primary tumours was performed through IHC staining of the formalin-fixed paraffin-embedded tissue blocks using Dako kits (Denmark) including the specific monoclonal antibodies [14], [15]. Other recorded subtypes included: -ER (positive)/PR (negative)/HER2 (positive); -ER (negative)/PR (positive)/HER2 (positive); -ER (positive)/PR (negative)/HER2 (negative); and -ER (negative)/PR (positive)/HER2 (negative).…”

“…They usually respond well to hormonal treatment but poorly to conventional chemotherapy. While Luminal A could be adequately controlled with endocrine treatment, luminal B (triple positive TP) phenotypes often tend to be more proliferative, yielding relatively higher grade and recurrent tumours; thus, recommending combined chemotherapy and hormonal treatment [10], [14].…”

Diagnosis of triple negative breast cancer based on radiomics signatures extracted from preoperative contrast-enhanced chest computed tomography

“…Immunohistochemistry assessments were made for the expression of ER, PR and HER2 as described previously [25,26]. Breast cancers were classified into luminal A, luminal B, HER2 overexpression and triple negative (TN).…”