Abstract. p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.
Abstract. the aim of this study was to compare the sensitivity of the serological level of anti-p53 antibodies in breast cancer patients and to correlate its expression level with patient age, histological stage and grade of tumor differentiation. total p53 protein expression (mutant and wild-type) was also determined in the breast cancer tissues using immunohistochemistry (ihc). the serological levels of mutant p53 expression were found to be age-dependent, reaching the highest level at 50 years of age. Faint or low detection was observed in patients ≤30 years of age. Anti-p53-antibodies were detected in patients ≤40 and ≥61 years of age. The serological levels of mutant p53 protein were highly detected in all stages of breast cancer, including the early stages. however, anti-p53 antibodies reached a high level of detection only in stage iii breast carcinomas. no expression was found in patients with benign breast disease. the detection of p53 mutations was dependent on the grade of tumor differentiation, achieving the highest level in the poorly differentiated breast carcinomas. results from ihc were highly correlated with serological p53 mutational analysis. Our findings indicate that mutant p53 in serum is a promising novel parameter for the evaluation of cellular biology and the prognosis of breast cancer from its early stages using blood samples. anti-p53 antibodies were demonstrated to be less sensitive in this study. it is also possible to use the expression of mutant p53 protein as a molecular marker to differentiate benign breast disease from breast carcinoma prior to surgery.
The objective of this pilot project was to investigate whether the breast fine needle aspiration (FNA) technique is a useful tool for determining the increased risk of breast cancer in patients with non-palpable breast lesions. FNA is a minimally invasive technique that isolates mammary epithelial cells from breast cells in the suspicious region. In this study, two FNA samples were collected from 12 patients. The level of HER2/neu expression at the mRNA level (in serum) was measured in each patient. As gene amplification is characteristic of cancer cells and may assist in diagnosis and prognostic assessment, it is crucial that gene amplification of HER2/neu in patients with non-palpable breast lesions is compared to breast biopsy results. In serum, the level of HER2/neu was determined by ELISA assay. Gene amplification was determined by PCR and confirmed by IHC employing monoclonal ERRB2 in the FNA sample. The results indicate that FNA has a good correlation with breast biopsy. FNA combined with mammographic imaging is a strong tool for determining favorable treatment options for patients.
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