Clinical significance of molecular alterations in histologically negative surgical margins of head and neck cancer patients
Clinical significance of molecular alterations in histologically negative surgical margins of head and neck cancer patients
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DOI：
10.1016/j.oraloncology.2011.10.018
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发表时间：
2012-03-01
期刊：
影响因子：
4.8
通讯作者：
Vettore, Andre Luiz
中科院分区：
文献类型：
--
作者：
de Carvalho, Ana Carolina;Kowalski, Luiz Paulo;Vettore, Andre Luiz
局部复发是头颈部鳞状细胞癌治疗失败的主要原因，而手术切缘残留的肿瘤细胞与复发有关。根据病理标本的组织学评估，认为手术切缘为阴性。然而，该方法在鉴定已经开始恶性转化但尚未发展出病理表型的细胞方面缺乏灵敏度。我们研究了评估PTHLH、EPCAM、MMP 9、LGALS 1和MET表达对检测组织学阴性手术切缘分子改变的有用性，并确定这些肿瘤相关改变与临床和预后参数的相关性。通过定量RT-PCR分析确定正常粘膜、HNSCC和阴性切缘样本中的差异基因表达。38%的组织学阴性手术切缘检查是边缘阳性的过度表达至少一个评估的基因。此外，手术切缘中MMP 9和PTHLH过表达分别与第二原发肿瘤的发展（p = 0.002）和局部控制率较低（对数秩检验p = 0.022; HR = 4.186; p = 0.035）相关。这些发现表明，肿瘤相关基因的过度表达在组织学阴性的手术切缘是一个常见的事件。使用qRT-PCR可能是检测实际阴性HNSCC手术切缘的有用工具，并且这些切缘中特定基因的过表达可能有助于识别具有较高发展第二原发肿瘤和局部复发风险的患者，从而帮助外科医生描绘HNSCC切除范围并帮助规划辅助治疗。(C)2011爱思唯尔有限公司保留所有权利。
The development of locoregional recurrence is the main reason for treatment failure in head and neck squamous cell carcinomas (HNSCC) and the remaining of tumor cells in surgical margins is associated with recurrence. Surgical margins are considered negative based on histologic assessment of the pathological specimen. However, this method lacks sensitivity in identifying cells that already started malignant transformation but have not yet developed a pathologic phenotype. We investigated the usefulness of assessing the expression of PTHLH, EPCAM, MMP9, LGALS1 and MET for the detection of molecular alterations in histologically negative surgical margins and determine the correlation of these tumor-related alterations with clinical and prognostic parameters. Differential gene expression was determined by quantitative RT-PCR analyses in normal mucosa, HNSCC and negative margin samples. Thirty-eight percent of the histologically negative surgical margins examined were margin-positive for overexpression of at least one of the genes evaluated. Moreover, MMP9 and PTHLH overexpression in the surgical margins was associated with the development of second primary tumors (p = 0.002) and lower rates of local control (log rank test p = 0.022; HR = 4.186; p = 0.035), respectively. These findings demonstrate that the overexpression of tumor-related genes in histologically negative surgical margins is a frequent event. The use of qRT-PCR may be an useful tool in detecting actually negative HNSCC surgical margins and the overexpression of specific genes in these margins could be helpful in the identification of patients with a higher risk of developing second primary tumors and local recurrences, thus aiding the surgeon in the delineation of the HNSCC resection extent and helping in the planning of adjuvant therapy. (C) 2011 Elsevier Ltd. All rights reserved.