MGMT activity in mucosal epithelium and squamous cell carcinoma of the head and neck

Area of Science:

• Oncology
• Molecular Biology
• Carcinogenesis

Background:

• Smoking and alcohol are primary causes of squamous cell carcinoma of the head and neck (SCCHN).
• O(6)-methylguanine-DNA methyltransferase (MGMT) plays a role in counteracting DNA mutations caused by carcinogens like smoke.
• Understanding MGMT's role in SCCHN development and precursor lesions is crucial for risk assessment and treatment strategies.

Purpose of the Study:

• To investigate the role of MGMT in SCCHN and its precursor lesions (SIN).
• To compare MGMT levels in normal mucosa (NM), blood lymphocytes (PBLCs), and cancerous/precancerous tissues.
• To determine the correlation between MGMT activity and clinical parameters in SCCHN.

Main Methods:

• Quantification of MGMT activity in normal mucosa (NM), blood lymphocytes (PBLCs), squamous intraepithelial neoplasia (SIN) grades II and III, and carcinoma in situ (CIS).
• Analysis of MGMT levels in relation to smoking status.
• Correlation analysis of MGMT activity with prognostic parameters and clinical outcomes in SCCHN patients.

Main Results:

• MGMT levels were lower in NM compared to PBLCs.
• Smoking significantly reduced MGMT in NM but not in PBLCs.
• MGMT activity showed a sequential increase from NM to SIN II/III and CIS.
• No significant correlation was found between MGMT levels and prognostic parameters or clinical course in SCCHN.

Conclusions:

• Smoking down-regulates MGMT in non-cancerous pharyngeal mucosa, potentially increasing susceptibility to mutations.
• Low MGMT activity in early dysplastic lesions (SIN) may elevate the risk of SCCHN development.
• The observed low MGMT activity in some advanced SCCHN cases suggests that chemotherapy using O(6)-alkylating agents could be a viable therapeutic option.