Second esophageal tumors in patients with head and neck squamous cell carcinoma: An assessment of clonal relationships

Patients with squamous cell carcinoma of the head and neck (HNSCC) often de velop second carcinomas elsewhere in the upper aerodigestive tract. Some of these paired tumors share a common origin, reflecting the ability of a sin gle progenitor cell to replicate, expand, and populate contiguous regions o f the upper aerodigestive tract-a process referred to as clonal expansion. The geographical limitations of clonal expansion, however, have not been ad equately addressed. For example, it is not known whether a neoplastic clone from the oral cavity, pharynx, or larynx can migrate to the esophagus, We compared paired tumors from 16 patients with HNSCC and a second squamous ce ll carcinoma of the esophagus (ESCC) for patterns of allelic loss on chromo somal arms 3p, 9p, and 17p, Losses at these loci occur early during neoplas tic transformation of the respiratory tract. In 14 cases (87%), the paired tumors had discordant patterns of allelic loss, suggesting that these tumor s were not clonally related. Conversely, two (13%) of the 16 paired tumors had identical genetic alterations, which suggests clonal expansion as the m echanism underlying tumor multifocality. One clone spread from the hypophar ynx into the cervical esophagus, and the other spread from the tonsil to th e distal esophagus, Although most second ESCCs appear to arise as independe nt neoplasms, a clonal population of neoplastic cells is capable of traveli ng across substantial distances to give rise to second tumors at different anatomical sites.