Garrel Renaud, Dromard Mathilde, Costes Valérie, Barbotte Eric, Comte Frédéric, Gardiner Quentin, Cartier César, Makeieff Marc, Crampette Louis, Guerrier Bernard, Boulle Nathalie
Departments of Head and Neck Surgery, Montpellier Teaching Hospital, Montpellier, France.
Clin Cancer Res. 2006 Apr 15;12(8):2498-505. doi: 10.1158/1078-0432.CCR-05-2136.
The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only. However, intraoperative + diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry. Real-time quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with intraoperative use, proving highly sensitive in detecting molecular markers. This study postoperatively assessed the accuracy of quantitative RT-PCR in staging patients from their SLN.
A combined analysis on the same SLN by serial step sectioning with immunohistochemistry and quantitative RT-PCR targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with oral or oropharyngeal squamous cell carcinoma and 10 control subjects.
From 71 lymph nodes examined, mRNA levels (KRT) were linked to metastasis size for the three cytokeratins studied (Pearson correlation coefficient, r = 0.89, 0.73, and 0.77 for KRT 5, 14, and 17 respectively; P < 0.05). Histopathology-positive SLNs (macro- and micrometastases) showed higher mRNA values than negative SLNs for KRT 17 (P < 10(-4)) and KRT 14 (P < 10(-2)). KRT 5 showed nonsignificant results. KRT 17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 mum. Smaller micrometastases and isolated tumor cells did not provide results above the background level. Receiver operating characteristic curve analysis for KRT 17 identified a cutoff value where patient staging reached 100% specificity and sensitivity for macro- and micrometastases.
Quantitative RT-PCR for SLN staging in cN(0) patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.
头颈部鳞状细胞癌前哨淋巴结（SLN）检测的主要目标是仅将颈部清扫术局限于pN+病例。然而，使用当前的金标准——免疫组织化学连续切片，无法常规进行术中诊断。实时定量逆转录聚合酶链反应（RT-PCR）可能适用于术中使用，在检测分子标志物方面具有高度敏感性。本研究术后评估了定量RT-PCR对患者SLN分期的准确性。
对18例连续的口腔或口咽鳞状细胞癌患者和10例对照受试者的同一SLN进行了免疫组织化学连续切片和靶向细胞角蛋白5、14和17的定量RT-PCR联合分析。
在所检测的71个淋巴结中，研究的三种细胞角蛋白的mRNA水平（KRT）与转移灶大小相关（KRT 5、14和17的Pearson相关系数分别为r = 0.89、0.73和0.77；P < 0.05）。组织病理学阳性的SLN（宏观和微观转移灶）的KRT 17（P < 10(-4)）和KRT 14（P < 10(-2)）mRNA值高于阴性SLN。KRT 5结果无统计学意义。KRT 17似乎是诊断大小>450μm微观转移灶的最准确标志物。较小的微观转移灶和孤立肿瘤细胞未得出高于背景水平的结果。KRT 17的受试者工作特征曲线分析确定了一个临界值，此时患者分期对宏观和微观转移灶的特异性和敏感性均达到100%。
定量RT-PCR用于口腔和口咽鳞状细胞癌cN(0)患者的SLN分期似乎是一种有前景的方法。
