The promoter region of the detoxifying gene GSTP

The promoter region of the detoxifying gene, GSTP1, is commonly hypermethylated in the promoter region in prostate adenocarcinoma and hepatocellular carcinoma,38, 39 but it was not hypermethylated in either oral cancer tissue, adjacent mucosa, or normal oral mucosa, as previously reported. The regulation of GSTP1 WS 3 in OSCC might not occur through promoter methylation.
Acknowledgments This study was supported by grants from Taichung Veterans General Hospital (TCVGHC9301) and the National Science Council (NSC93-2314-B-075A-016).
Introduction Buccal cancer rapidly increases its incidence in Taiwan. Clinically, buccal cancer characterizes a low neck nodal involvement but high primary tumor aggressiveness, representing a unique disease entity.[2], [3], [4] Radical surgery is the initial treatment of choice in patients with resectable disease; however, cancer recurrence is not uncommon after radical surgery alone.[2], [5] Thus, post-operative radiotherapy (RT) with or without chemotherapy is recommended for patients with adverse features, such as pT3-4, pN1-3, and positive but not close surgical margin. The role of unexpected close pathological margin after radical surgery may be underestimated. First, unexpected close surgical margin has been proposed to represent, at least partly, the intrinsic bio-aggressiveness of cancer cells. Second, patients with close margin are at a higher risk for cancer recurrence than patients with wide margin.[8], [9], [10], [11] However, close margin alone does not independently guide post-operative therapies.[5], [6], [12], [13] This discrepancy reveals a clinical debate. Further stratification in this subgroup of patients is essential. In this regard, we previously investigated resected buccal cancer patients who had a close surgical margin of⩽3 mm. We observed that very close surgical margin of⩽1 mm may be a good stratifying factor, but this pathological factor alone fails to predict overall survival. Thus, exploring a bio-predictor to complement the pathological factor is reasonable for further stratifying this group of patients.[7], [14], [15] DNA promoter hypermethylation is an important mechanism in epigenetic modulation of gene expression.[16], [17], [18] When the promoter CpG island of a gene is hypermethylated, the transcription and its associated function of the gene will be subsequently altered.[19], [20], [21] In human cancers, we and the others have demonstrated that promoter hypermethylation of tumor suppressor genes is an important cancer-specific event.[22], [23], [24], [25] More notably, its role in predicting clinical outcomes has been well recognized in cancer patients.[19], [26], [27], [28] For example, in oral squamous cell carcinoma, promoter hypermethylation of RASSF1A (Ras association domain family protein 1A) and DAPK (Death-associated protein kinase) have been observed to correlate with poor prognosis after RT and after a wide-margin surgery, respectively. However, the role of aberrant promoter hypermethylation is still not well defined in resected buccal cancer patients who had an unexpected close surgical margin.