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  • Title: Head and neck squamous cell carcinoma: mismatch repair immunohistochemistry and promoter hypermethylation of hMLH1 gene.
    Author: Tawfik HM, El-Maqsoud NM, Hak BH, El-Sherbiny YM.
    Journal: Am J Otolaryngol; 2011; 32(6):528-36. PubMed ID: 21353335.
    Abstract:
    UNLABELLED: Squamous cell carcinomas of the head and neck are the sixth most frequently occurring cancers and the seventh leading cause of cancer-related deaths worldwide. Epigenetic alteration, using promoter hypermethylation of hMLH1 gene, is important for the development of head and neck squamous cell carcinoma (HNSCC). AIM OF THIS WORK: The aim of the present study is to analyze the relationship between protein expression and promoter hypermethylation of the hMLH1 gene in HNSCC and correlating inactivation of this gene with clinical parameters. MATERIALS AND METHODS: Paired normal and tumor specimens from 49 patients with HNSCC were collected from Otolaryngology Department, Minia University Hospital, from 2006 to 2009. We analyzed hMLH1 protein expression and promoter hypermethylation by immunohistochemical and methylation-specific polymerase chain reaction (MSP). RESULTS: Decreased hMLH1 protein expression and hMLH1 promoter hypermethylation were shown in 15 (30.6%) and 14 (28.6%) cases, respectively. Eleven cases showed dysplasia and or carcinoma in situ in the surface squamous epithelia, and all were positively stained for the hMLH1 protein. hMLH1 promoter hypermethylation was detected in 10 (20.4%) cases of normal-appearing squamous mucosa adjacent to invasive carcinoma. Thirteen (86.7%) of 15 cases that were negative for the hMLH1 protein showed promoter hypermethylation, whereas 33 (97%) of 34 cases positive for the protein were negative of promoter methylation. Promoter hypermethylation was detected in 1 (7.1%) case in which invasive tumor cells were moderately positive for the hMLH1 protein. No significant correlation was observed between hMLH1 protein expression or hMLH1 promoter hypermethylation and any of clinicopathologic parameters. CONCLUSIONS: hMLH1 gene may be detected early in head and neck squamous carcinogenesis. Promoter hypermethylation is an important mechanism for hMLH1 gene inactivation in HNSCC.
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