头颈部鳞状细胞癌：错配修复免疫组织化学和 hMLH1 基因启动子超甲基化。

Head and neck squamous cell carcinoma: mismatch repair immunohistochemistry and promoter hypermethylation of hMLH1 gene.

机构信息

Department of Pathology, Faculty of Medicine Minia University, Egypt.

出版信息

Am J Otolaryngol. 2011 Nov-Dec;32(6):528-36. doi: 10.1016/j.amjoto.2010.11.005. Epub 2011 Feb 24.

DOI:10.1016/j.amjoto.2010.11.005

PMID: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.

摘要

目的

本研究旨在分析头颈鳞状细胞癌（HNSCC）中 hMLH1 基因蛋白表达与启动子甲基化的关系，并将该基因的失活与临床参数相关联。

材料和方法

收集了 2006 年至 2009 年期间来自米尼亚大学医院耳鼻喉科的 49 例 HNSCC 患者的配对正常和肿瘤标本。我们通过免疫组织化学和甲基化特异性聚合酶链反应（MSP）分析 hMLH1 蛋白表达和启动子甲基化。

结果

15 例（30.6%）和 14 例（28.6%）分别显示 hMLH1 蛋白表达降低和 hMLH1 启动子甲基化。11 例表面鳞状上皮出现发育不良或原位癌，均对 hMLH1 蛋白呈阳性染色。在紧邻浸润性癌的正常外观鳞状黏膜中检测到 10 例（20.4%） hMLH1 启动子甲基化。15 例 hMLH1 蛋白阴性的病例中有 13 例（86.7%）存在启动子甲基化，而 34 例 hMLH1 蛋白阳性的病例中有 33 例（97%）无启动子甲基化。在 hMLH1 蛋白阳性的侵袭性肿瘤细胞中度阳性的 1 例中检测到启动子甲基化。hMLH1 蛋白表达或 hMLH1 启动子甲基化与任何临床病理参数之间均无显著相关性。