Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Abstract

Clinical staging of cervical lymph nodes from patients with squamous cell carcinoma of the head and neck (SCCHN) has only 50% accuracy compared with definitive pathologic assessment. Consequently, both clinically positive and clinically negative patients frequently undergo neck dissections that may not be necessary. To address this potential overtreatment, sentinel lymph node (SLN) biopsy is currently being evaluated to provide better staging of the neck. However, to fully realize the potential improvement in patient care afforded by the SLN procedure, a rapid and accurate SLN analysis is necessary. We used quantitative reverse transcription--PCR (QRT-PCR) to screen 40 potential markers for their ability to detect SCCHN metastases to cervical lymph nodes. Seven markers were identified with good characteristics for identifying metastatic disease, and these were validated using a set of 26 primary tumors, 19 histologically positive lymph nodes, and 21 benign nodes from patients without cancer. Four markers discriminated between positive and benign nodes with accuracy > >97% but only one marker, pemphigus vulgaris antigen (PVA), discriminated with 100% accuracy in both the observed data and a statistical bootstrap analysis. A rapid QRT-PCR assay for PVA was then developed and incorporated into a prototype instrument capable of performing fully automated RNA isolation and QRT-PCR. The automated analysis with PVA provided perfect discrimination between histologically positive and benign lymph nodes and correctly identified two lymph nodes with micrometastatic tumor deposits. These assays were completed ( from tissue to result) in f f30 minutes, thus demonstrating the feasibility of intraoperative staging of SCCHN SLNs by QRT-PCR. (Cancer Res 2005; 65(6): 2147-56)

Serum Vascular Endothelial Growth Factor-A (VEGF-A) as a Biomarker in Squamous Cell Carcinoma of Head and Neck Patients Undergoing Chemoradiotherapy

“…Patients with SCCHN often present with symptoms at a late stage and high recurrence rate and lower survival rate after treatment, especially in those with neck lymph node metastasis (Ferris et al, 2005;Wang et al, 2013). Despite of improved modern therapeutic interventions, the 5-year survival rate for this disease has improved only marginally over the past decade and recurrent disease is observed in 50% of the patients (Le et al, 2003;Eto et al, 2007;Pulte et al, 2010).…”

Detection of occult carcinomatous diffusion in lymph nodes from head and neck squamous cell carcinoma using real-time RT–PCR detection of cytokeratin 19 mRNA

“…These data suggest that real-time RT -PCR could potentially increase the sensitivity of routine pathological examination Ferris et al, 2005), and could therefore be used routinely to examine all nodes removed during neck dissection that are negative on standard histopathologic examination.…”

Pemphigus vulgaris antigen mRNA quantification for the staging of sentinel lymph nodes in head and neck cancer

“…Therefore, as the CK17 mRNA 'cutoff' value separating positive and negative nodes overlapped, more robust tumour-related markers clearly need to be validated. Recently, Ferris et al (2005) screened 40 potential markers using primary tumour and gross metastatic deposits and compared these with benign nodes. Among the screened markers, SCCA and PVA mRNA quantification provided a remarkable discrimination between positive and benign lymph nodes, and were thus proposed as potentially relevant markers for the staging of cervical lymph nodes in HNSCC.…”

“…Therefore, molecular test accuracy had to be improved so as to minimise the risk of 'falsenegative' cases before proposing an effective clinical intraoperative application of such an approach. Recently, Pemphigus vulgaris antigen (PVA) and squamous cell carcinoma antigen (SCCA) have been highlighted as potential tumour-specific mRNA markers for the molecular staging of cervical lymph nodes in HNSCC (Ferris et al, 2005). However, to our knowledge, the reliability and accuracy of these markers has not been evaluated elsewhere for the molecular diagnosis of occult SLN metastases.…”