FHIT基因的反复缺失及其对早期口腔鳞状细胞癌淋巴转移的影响。

Recurrent loss of the FHIT gene and its impact on lymphatic metastasis in early oral squamous cell carcinoma.

作者信息

Joo Young-Hoon, Park Sung-Won, Jung Seung-Hyun, Lee Yeon-Soo, Nam In-Chul, Cho Kwang-Jae, Park Jun-Ook, Chung Yeun-Jun, Kim Min-Sik

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, College of Medicine, Catholic University of Korea, Seoul, Korea.

出版信息

Acta Otolaryngol. 2013 Sep;133(9):992-9. doi: 10.3109/00016489.2013.795289.

DOI:10.3109/00016489.2013.795289

PMID:23944951

Abstract

CONCLUSION

Our findings show that copy number loss of FHIT is associated with lymph node metastasis (LNM) and suggest that the down-regulation of Fhit indicates poor prognosis in early oral squamous cell carcinoma (OSCC).

OBJECTIVES

The purpose of this study was to identify alterations in genetic markers related to LNM in early OSCC.

METHODS

Genome-wide copy number alterations were analyzed in 14 early OSCCs with (n = 7) or without (n = 7) cervical LNM using 180K array-comparative genomic hybridization. To explore the prognostic implications of the most significantly associated genetic alteration with cervical LNM, immunohistochemical analysis was conducted in 30 OSCCs.

RESULTS

A total of 11 recurrently altered regions (RARs) were identified in the 14 OSCC cases. Six RARs on chromosomes 3p26-3p14, 5q22, and 9p21 were found to be significantly more common in early OSCC with LNM (p < 0.05). Among these, loss of 3p14.2 (where the FHIT gene is located) was the most frequent (five of seven patients with LNM, and none of seven without LNM), and most significantly associated with cervical LNM (p = 0.005). Fhit immunohistochemical staining of 30 OSCCs showed that Fhit negativity was associated with cervical LNM (p = 0.032) and poor disease-specific survival (p = 0.045).

摘要

结论

我们的研究结果表明，FHIT基因的拷贝数缺失与淋巴结转移（LNM）相关，并提示Fhit表达下调预示早期口腔鳞状细胞癌（OSCC）预后不良。

目的

本研究旨在确定早期OSCC中与LNM相关的基因标志物改变。

方法

采用180K阵列比较基因组杂交技术，对14例伴有（n = 7）或不伴有（n = 7）颈部LNM的早期OSCC进行全基因组拷贝数改变分析。为探讨与颈部LNM最显著相关的基因改变的预后意义，对30例OSCC进行免疫组化分析。

结果

在14例OSCC病例中总共鉴定出11个反复改变的区域（RARs）。发现3号染色体p26 - p14、5号染色体q22和9号染色体p21上的6个RARs在伴有LNM的早期OSCC中更为常见（p < 0.05）。其中，3p14.2（FHIT基因所在位置）缺失最为频繁（7例伴有LNM的患者中有5例，7例不伴有LNM的患者中无一例），且与颈部LNM显著相关（p = 0.005）。对30例OSCC进行Fhit免疫组化染色显示，Fhit阴性与颈部LNM（p = 0.032）及较差的疾病特异性生存率（p = 0.045）相关。