MGMT expression in oral precancerous and cancerous lesions: Correlation with progression, nodal metastasis and poor prognosis

Alkylation of DNA at the O-6 position of guanine is a critical step in the induction of mutations by carcinogenic and chemotherapeutic alkylating agents. O-6-methylguanine-DNA methyltransferase (MGMT) is an enzyme that removes mutagenic adducts from the O-6 position of guanine, thereby protecting the genome against guanine to adenine transitions. We hypothesized that alteration in MGMT expression might occur in early stages of development of oral cancer and be associated with disease progression. Immunohistochemical analysis of MGMT expression was carried out in 107 oral squamous cell carcinomas (OSCCs), 78 oral precancerous lesions (OPLs) (58 hyperplasias and 20 dysplasias) and 30 histologically normal oral tissues and correlated with clinicopathological parameters as well as major risk factors. Decreased MGMT expression was observed as early as in hyperplasia (p = 0.003; Odd's Ratio (OR) = 5.0).