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Published on: July 25, 2011
Topoisomerase IIa protein expression analysis in oral squamous cell carcinoma
Vasileios Papanikolaou1, Efthymios Kyrodimos, Nicholas Mastronikolis
11st ENT Department, Hippocration Hospital, University of Athens, Athens, Greece.
Purpose:
Topoisomerases represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase II alpha (Topo IIa-gene location 17q21) is a critical gene associated with response to chemotherapeutic agents such as anthracyclines especially in breast adenocarcinoma. Our aim was to investigate the role of aberrant Topo IIa protein expression in oral squamous cell carcinoma (OSCC).
Methods:
Fifty formalin-fixed, paraffin-embedded primary OSCCs tissue sections were used. Immunohistochemistry was performed using an anti- Topo IIa antibody. Digital image analysis was implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei.
Results:
Topo IIa protein overexpression (moderate to high immunostaining intensity values) was observed in 29/50 (58%) tissue cores, whereas low expression rates were detected in the remaining cases (21/50;42%). Topo IIa overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.037) and also with human papillomavirus (HPV) positivity (p=0.029). No other statistical correlations were identified.
Conclusions:
Topo IIa overexpression is observed in significant subsets of OSCCs correlated with the grade of differentiation. Additionally, HPV persistent infection is associated with increased Topo IIa protein expression levels. Topo IIa expression analysis should be critical for identifying patients eligible for applying specific chemotherapeutic strategies based on anti-Topo IIa agents.
Insights
Topoisomerase II alpha (Topo IIa) overexpression is common in oral squamous cell carcinoma (OSCC), linked to tumor differentiation and HPV. This finding may guide targeted chemotherapy for OSCC patients.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Topoisomerases are crucial enzymes regulating DNA topology.
- Topoisomerase II alpha (Topo IIa) is implicated in cancer therapy response, particularly in breast cancer.
- The role of Topo IIa in oral squamous cell carcinoma (OSCC) remains underexplored.
Purpose of the Study:
- To investigate the expression patterns of Topo IIa protein in OSCC.
- To determine the correlation between Topo IIa expression and clinicopathological features of OSCC.
- To assess the potential of Topo IIa as a biomarker for therapeutic strategies in OSCC.
Main Methods:
- Analysis of 50 formalin-fixed, paraffin-embedded OSCC tissue samples.
- Immunohistochemistry using an anti-Topo IIa antibody.
- Quantitative digital image analysis for objective protein expression assessment.
Main Results:
- Topo IIa overexpression (moderate to high staining) was detected in 58% of OSCC cases.
- Topo IIa expression significantly correlated with tumor differentiation grade (p=0.037).
- A significant association was found between Topo IIa expression and human papillomavirus (HPV) positivity (p=0.029).
Conclusions:
- Topo IIa protein is overexpressed in a substantial subset of OSCC.
- Increased Topo IIa expression is linked to tumor differentiation and HPV infection in OSCC.
- Topo IIa expression analysis may aid in selecting OSCC patients for anti-Topo IIa-based chemotherapy.
