Related Experiment Videos
Alteration of p53 gene structure and function in laryngeal squamous cell cancer
W Golusinski1, J Olofsson, Z Szmeja
1Department of Otolaryngology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
Abstract:
The p53 gene is known as an anti-oncogene that manifests its function by controlling the cell cycle and is responsible for apoptosis of cells with unrepaired DNA. An accelerated p53 protein synthesis is the first response of a cell following DNA damage. However, mutations of the p53 gene can disturb protein synthesis or may be responsible for synthesis of a changed protein unable to control the cell cycle. Laryngeal tissue specimens from 120 patients were tested by immunohistopathological staining to detect mutated wild-type p53 protein. It was found that p53-positive specimens correlated with TNM staging and histopathological grading. Another indication of entering the cell cycle and undertaking an active proliferation by laryngeal cells was shown by detection of proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen, which appeared in proliferating cells (late G1, S-G2 and M phase), but was absent in resting cells. Scoring of the staining for p53 protein, PCNA and Ki67 correlated with each other. DNA from 40 specimens was then isolated, amplified by polymerase chain reaction and analysed by single-strand conformation polymorphism and DNA sequencing for mutation in the p53 gene. Fifteen DNA samples were found to be positive, while mutations were detected in exons 5-8 in 13 samples. The majority of mutations were found in tissue specimens from T3 and T4 tumors. A possible explanation is almost half was attributable to genotoxic effects of tobacco smoking. Changes in the p53 gene and its products may also reflect early changes in laryngeal carcinogenesis and be of prognostic value.
Insights
Mutations in the p53 gene, a tumor suppressor, are linked to laryngeal cancer progression and severity. Detecting p53 protein and proliferation markers aids in understanding cancer development and may offer prognostic insights.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 gene acts as an anti-oncogene, regulating the cell cycle and apoptosis in response to DNA damage.
- Accelerated p53 protein synthesis is an early cellular response to DNA damage.
- p53 gene mutations can disrupt cell cycle control, potentially leading to cancer.
Purpose of the Study:
- To investigate the correlation between p53 gene mutations and laryngeal cancer characteristics.
- To assess the utility of p53, PCNA, and Ki67 as biomarkers in laryngeal carcinogenesis.
- To explore the prognostic value of p53 alterations in laryngeal tumors.
Main Methods:
- Immunohistopathological staining of 120 laryngeal tissue specimens to detect p53, PCNA, and Ki67.
- Analysis of p53 gene mutations in 40 specimens using polymerase chain reaction, single-strand conformation polymorphism, and DNA sequencing.
- Correlation of biomarker expression with TNM staging and histopathological grading.
Main Results:
- p53-positive specimens showed a correlation with advanced TNM staging and higher histopathological grading.
- Expression of p53, PCNA, and Ki67 proteins correlated with each other and with cellular proliferation.
- p53 gene mutations were identified in 13 of 40 analyzed samples, predominantly in exons 5-8 and in advanced T3/T4 tumors.
- Tobacco smoking may contribute significantly to p53 mutations in laryngeal cancer.
Conclusions:
- p53 gene alterations are associated with laryngeal cancer progression and may serve as an early indicator of carcinogenesis.
- The combined assessment of p53, PCNA, and Ki67 expression offers valuable insights into laryngeal tumor behavior.
- p53 gene mutations and protein expression patterns hold potential prognostic significance for laryngeal cancer patients.