Overexpression of p53 protein is a marker of poor prognosis in Mexican women with breast cancer

Abstract

Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase 2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.

Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis

“…Mutant p53 proteins usually causes the accumulation of p53 protein at a very high levels, and the mutant p53 protein itself can inhibit normal p53 protein levels [ 11 ]. In recent years, several reports have shown that p53 expression can serve as a promising biomarker for predicting various tumors [ 14 – 19 ]. Many studies have also reported the prognostic value of p53 expression in RCC, but the results were still conflicting [ 20 – 41 ].…”

“…Mutant p53 cannot be effectively bound to DNA , and the p21 protein cannot act as the “stop signal” for cell division, which results in tumors formation [ 12 , 13 ]. It is reported that p53 expression predicts prognosis in various multiple cancer types including breast cancer [ 14 ], gastric cancer [ 15 ], multiple myeloma [ 16 ], colorectal cancer [ 17 ], cervical cancer [ 18 ], and oral cancer [ 19 ]. Many studies have investigated the prognostic role of p53 expression in RCC, but the results are conflicting [ 20 – 41 ].…”

Inhibin B suppresses anoikis resistance and migration through the transforming growth factor‐β signaling pathway in nasopharyngeal carcinoma

“…| 3425 between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, and visceral metastasis in breast cancer patients, 50 and patients with triple-negative breast cancer showed p53 protein overexpression, which resulted in lower survival. 51 In our study, the expression of p53 was upregulated in anoikis-resistant NPC cells with highly invasive and metastatic characteristics. Inhibition of INHBB can activate TGF-β function through the interaction of TGF-β and p53, 52 which could further improve p53 levels in metastatic NPC cells ( Figure S3).…”

“…The functional switching of TGF‐β is partially caused by p53 mutation or p53 inactivation during cancer progression . A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, and visceral metastasis in breast cancer patients, and patients with triple‐negative breast cancer showed p53 protein overexpression, which resulted in lower survival . In our study, the expression of p53 was upregulated in anoikis‐resistant NPC cells with highly invasive and metastatic characteristics.…”

Association Between Genetic Variant in the Promoter of Pri-miR-34b/c and Risk of Glioma

“…A meta-analysis conducted by De-Ke Jiang et al concluded that TP53 Arg72 carriers can significantly reduce the risk of esophageal cancer ( 36 ). In contrast, Dimas-Gonzalez et al reported that p53 protein was up-regulated in breast cancer ( 37 ). The TP53 Arg72Pro CC genotype may contribute to an increased risk of CRC, especially for rectal cancer and among Asians ( 38 ).…”