口腔鳞状细胞癌中的多种基因拷贝数改变：原发性和转移性肿瘤中 MYC、TP53、CCDN1、EGFR 和 ERBB2 状态的研究。

Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours.

机构信息

Department of Medicina i Dermatologia, Universitat Autònoma de Barcelona, Hospital del Mar, Parc de Salut Mar, Passeig Marítim 25-29, 08003 Barcelona, Spain.

出版信息

Br J Dermatol. 2010 Nov;163(5):1028-35. doi: 10.1111/j.1365-2133.2010.09947.x.

DOI:10.1111/j.1365-2133.2010.09947.x

PMID:20662834

Abstract

BACKGROUND

Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain.

OBJECTIVE

To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases.

METHODS

Fifty-one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs.

RESULTS

TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples (P < 0·005). Overexpression of p53, Myc, Cyclin D1, c-erbB-2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples (P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC.

CONCLUSIONS

In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases.

摘要

背景

口腔癌的发生被认为是由于遗传改变导致黏膜向浸润性癌的逐步转化。在口腔鳞状细胞癌（OSCC）中，已经报道了多种细胞遗传学异常，但它们的实际意义仍不确定。

目的

评估 CCND1、MYC、EGFR、ERBB2 和 TP53 在 OSCC 和淋巴结转移中的评估价值。

方法

纳入了 51 例连续的 OSCC 样本、9 例显示 OSCC 转移的淋巴结活检、16 例口腔白斑（OLK）活检、13 例口腔扁平苔藓（OLP）活检和 14 例正常口腔黏膜活检。回顾了临床和组织病理学特征。通过荧光原位杂交（FISH）和免疫组织化学（IHC）评估 CCND1、MYC、EGFR、ERBB2 癌基因和 TP53 肿瘤抑制基因的遗传和蛋白状态。将获得的结果与 OSCC 的临床特征和结果进行比较。

结果

在 OSCC 和淋巴结样本中，与 OLK 和 OLP 样本相比，TP53 基因缺失以及 MYC、ERBB2、CCND1 和 EGFR 拷贝数增加和扩增的比例更高（P<0.005）。在恶性样本中，p53、Myc、Cyclin D1、c-erbB-2 和表皮生长因子受体（EGFR）的过表达比良性样本更为常见（P<0.05）。在 MYC、EGFR 和 CCND1 研究中，显示了 FISH 和 IHC 结果之间的相关性。在所研究的基因座中，两种或更多种遗传异常仅在原发性和转移性 OSCC 中被检测到。

结论

在我们的研究中，FISH 检测到的 TP53、MYC、CCND1、ERBB2 和 EGFR 的遗传异常在炎症性病变中不存在，在前期病变中罕见，在肿瘤性病变中常见。评估 TP53、MYC、CCND1、ERBB2 和 EGFR 的遗传状态可能是在组织病理学具有挑战性的情况下，区分良性和恶性口腔病变的附加诊断工具。