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采用 p16(INK4A)、细胞血红素结合蛋白、E-钙黏蛋白和 TMEFF2 启动子甲基化对口腔鳞状细胞癌手术切缘进行分子分期。

Molecular staging of surgical margins in oral squamous cell carcinoma using promoter methylation of p16(INK4A), cytoglobin, E-cadherin, and TMEFF2.

机构信息

Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.

出版信息

Ann Surg Oncol. 2013 Aug;20(8):2796-802. doi: 10.1245/s10434-012-2713-8. Epub 2012 Oct 31.

Abstract

BACKGROUND

Local recurrence in oral squamous cell carcinoma (OSCC) despite clear surgical margins may indicate the presence of residual, sub-microscopic disease. Molecular assessment of surgical margins may provide a greater prognostic sensitivity compared to histopathology. We aimed to determine whether promoter methylation in deep and mucosal resection margins can predict recurrence in OSCC.

METHODS

Forty-eight consecutive OSCC cases were recruited and a 5 mm(3) tumor sample plus 5 deep and 5 mucosal margin samples were snap frozen. Clinical, pathological, adjuvant therapy, and outcome data were recorded. Tumors were informative if >5 % promoter methylation was found for ≥1 of 4 genes using qMSP. Margins were declared molecularly positive if >1 % promoter methylation was found in any margin.

RESULTS

Thirty (63 %) of 48 cases were methylation informative. Mucosal margin samples were largely positive for methylation (26 of 30, 87 %), indicating the presence of field cancerization. Methylation at ≥1 gene promoters in ≥1 deep margin correlated with the presence of close/involved mucosal margins (P = 0.027) and increased pT status (P = 0.027) but not the status of deep margins, recurrence, or survival.

CONCLUSIONS

The current gene panel did not add prognostic information to histopathological reporting of resection margins. Future efforts should concentrate on improving gene selection, informativity, and assay performance in the patient group with intermediate indications for adjuvant therapy.

摘要

背景

口腔鳞状细胞癌(OSCC)即使手术切缘清晰,仍有局部复发,这可能表明存在残留的亚微观疾病。手术切缘的分子评估与组织病理学相比,可能具有更高的预后敏感性。我们旨在确定深层和黏膜切除切缘中的启动子甲基化是否可以预测 OSCC 的复发。

方法

连续招募了 48 例 OSCC 病例,并对 5 例肿瘤样本加 5 例深层和 5 例黏膜边缘样本进行冷冻。记录了临床、病理、辅助治疗和结局数据。如果 4 个基因中的≥1 个基因的启动子甲基化率>5%,则认为肿瘤是信息性的。如果在任何边缘发现>1%的启动子甲基化,则认为边缘是分子阳性。

结果

48 例中有 30 例(63%)为甲基化信息性。黏膜边缘样本的甲基化率很高(30 例中的 26 例,87%),表明存在癌前病变的场效应。≥1 个深层边缘中≥1 个基因启动子的甲基化与近距离/受累黏膜边缘的存在相关(P=0.027)和增加的 pT 状态(P=0.027),但与深层边缘的状态、复发或生存无关。

结论

目前的基因面板并未为切缘的组织病理学报告提供预后信息。未来的研究应集中于改善基因选择、信息性和在具有辅助治疗中等指征的患者群体中的检测性能。

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