The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana

Abstract

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.

Elevated Pre-Treatment Systemic Immuno-Inflammatory Indices, Triple-Negative Breast Cancer, and p53 Mutation are Associated with Early-Onset Breast Cancer in Southern Nigeria

“…In contrast, Vona-Davis et al [27] observed higher cases of obesity among patients with TNBC (50%) than non-TNBC cases (16%). The frequency of p53 expression in TNBC cases is like the prevalence rate reported in Ghana (31.0%) by Ameh-Mensah et al [28] but lower than the frequency rate reported in Morocco (41.0%) by Jouli et al [29]. Here, the frequency of BRCA2 loss in TNBC is higher than the prevalence rate reported by Jiagge et al [30] and Xie et al [31] in Ghana (40%) and China (20%), respectively.…”

“…The difference in BRCA2 expression in TNBC could be race and lifestyle-related. Studies have shown that a high expression of the p53 gene is associated with high-grade large-size and highly proliferative tumours with lymph node involvement, and risk of recurrence [28,29,32]. Thus, the concomitant high expression of p53 and moderate to low expression of BRCA2 in this study could be an early immune response to aggressive tumours.…”

“…The frequency of p53 expression in TNBC cases is like the prevalence rate reported in Ghana (31.0%) by Ameh-Mensah et al . [28] but lower than the frequency rate reported in Morocco (41.0%) by Jouli et al . [29].…”

Codelivery of Que and BCL-2 siRNA with Lipid–Copolymer Hybrid Nanocomplexes for Efficient Tumor Regression

“…Encouragingly, the combination of Que and siBCL2 (Que, 20 μg/mL, N/P = 20) further displayed significant anti-proliferative ability, which revealed the lowest cell viability of 26.8 and 27.8% in 4T1 and MDA-MB-231 cells, respectively, highlighting their potent synergistic anti-tumor effect (Figure E,F) . In addition, increased Bcl-2 expression has been observed in TNBC . Hence, BCL-2 silencing may sensitize tumor cells to co-administered Que and thereby improve therapeutic efficacy.…”

“…18 In addition, increased Bcl-2 expression has been observed in TNBC. 27 Hence, BCL-2 silencing may sensitize tumor cells to co-administered Que and thereby improve therapeutic efficacy. The CI of Que/Cy5-siRNA@BioMICs was calculated by CompuSyn software, and the values of CI (Fa = 0.5) of 0.21 and 0.32 in MDA-MB-231 and 4T1 cells, respectively, indicated a synergistic effect (Figure 3H,I).…”