Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4330, USA.
Oral Oncol. 2013 Feb;49(2):93-101. doi: 10.1016/j.oraloncology.2012.08.001. Epub 2012 Sep 23.
The diagnosis of cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) patients constitutes an essential requirement for clinical staging and treatment selection. However, clinical assessment by physical examination and different imaging modalities, as well as by histological examination of routine lymph node cryosections can miss micrometastases, while false positives may lead to unnecessary elective lymph node neck resections. Here, we explored the feasibility of developing a sensitive assay system for desmoglein 3 (DSG3) as a predictive biomarker for lymph node metastasis in HNSCC.
DSG3 expression was determined in multiple general cancer- and HNSCC-tissue microarrays (TMAs), in negative and positive HNSCC metastatic cervical lymph nodes, and in a variety of HNSCC and control cell lines. A nanostructured immunoarray system was developed for the ultrasensitive detection of DSG3 in lymph node tissue lysates.
We demonstrate that DSG3 is highly expressed in all HNSCC lesions and their metastatic cervical lymph nodes, but absent in non-invaded lymph nodes. We show that DSG3 can be rapidly detected with high sensitivity using a simple microfluidic immunoarray platform, even in human tissue sections including very few HNSCC invading cells, hence distinguishing between positive and negative lymph nodes.
We provide a proof of principle supporting that ultrasensitive nanostructured assay systems for DSG3 can be exploited to detect micrometastatic HNSCC lesions in lymph nodes, which can improve the diagnosis and guide in the selection of appropriate therapeutic intervention modalities for HNSCC patients.
对头颈鳞状细胞癌(HNSCC)患者的颈部淋巴结转移进行诊断是临床分期和治疗选择的基本要求。然而,通过体格检查和不同的成像方式进行临床评估,以及对常规淋巴结冷冻切片进行组织学检查,可能会遗漏微转移灶,而假阳性可能导致不必要的选择性颈部淋巴结切除术。在这里,我们探讨了开发一种用于桥粒芯糖蛋白 3(DSG3)的敏感检测系统作为预测 HNSCC 淋巴结转移的生物标志物的可行性。
在多个通用癌症和 HNSCC 组织微阵列(TMA)、阴性和阳性 HNSCC 转移性颈部淋巴结以及各种 HNSCC 和对照细胞系中确定 DSG3 的表达。开发了一种纳米结构免疫阵列系统,用于超灵敏检测淋巴结组织裂解物中的 DSG3。
我们证明 DSG3 在所有 HNSCC 病变及其转移性颈部淋巴结中高度表达,但在未受侵袭的淋巴结中不存在。我们表明,即使在包括极少数侵袭性 HNSCC 细胞的人类组织切片中,也可以使用简单的微流控免疫阵列平台快速且高灵敏度地检测 DSG3,从而区分阳性和阴性淋巴结。
我们提供了一个原理证明,支持可以利用用于 DSG3 的超灵敏纳米结构检测系统来检测淋巴结中的微小 HNSCC 病变,这可以改善诊断并指导 HNSCC 患者选择适当的治疗干预方式。