Molecular Determination of Primary Versus Metastatic Squamous Cell Carcinoma (SCC) of the Lung in the Context of SCC of the Head and Neck (H/N)

Abstract

Patients with SCC H/N are at a high risk of developing lung SCC. Given similar histology, the distinction between metastatic and primary SCC is difficult. Thus, molecular methods may be clinically useful to evaluate tumor relatedness. We previously showed that assessment of microsatellite allelic variation can be utilized to discriminate multiple primary versus metastatic SCC of H/N. The goal of this study was to refine this methodology using fluorescent‐labeled primers with automated detection. Genomic DNA was extracted from paraffin‐embedded tumor samples from nine patients who had undergone resection of SCC of both the H/N and lung. Comparison was made between microsatellite PCR with PAGE analysis versus fluorescent product detection. Both methods yielded interpretable results. Metastatic lung SCC were characterized by either identical alleles or allelic losses as compared to SCC H/N, while metachronous primary SCC lung were characterized by discordant alleles to the SCC H/N. Fluorescent product detection is able to detect some allelic discordant which is not detectable by PAGE analysis. Fluorescent product detection is sensitive and high‐throughput. The results confirm that molecular methods can distinguish primary vs. metastatic SCC of the lung in the context of SCC H/N. Accurate characterization of these lesions may significantly impact clinical management strategies for these patients.