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Molecular Detection of Early-Stage Laryngopharyngeal Squamous Cell Carcinomas

Authors' Affiliations: Departments of ¹ Head and Neck Surgery, ² Genetics, and ³ Cancer Medicine, Institut Gustave-Roussy, Villejuif, France; ⁴ Department of Pathology, Centre René Huguenin, St. Cloud, France; ⁵ Molecular Carcinogenesis Unit, IARC, Lyon, France; and ⁶ Department of Thoraic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: François Janot, Department of Head and Neck Surgery, Institut Gustave-Roussy, 39 rue Camille Desmoulins, Villejuif 94805, France. Phone: 33-1-4211-4450; Fax: 33-1-4211-5273; E-mail: janot{at}igr.fr.

Purpose: We sought to determine whether early-stage laryngopharyngeal squamous cell carcinomas (SCC) can be detected through molecular analysis of exfoliated cells collected with the use of a pharyngoesophageal brush (PEB).

Experimental Design: Thirty-three patients with a single, untreated, early-stage (T1 or T2) SCC of the supraglottic larynx or pharynx underwent collection of cells with a PEB, followed by endoscopic biopsy of the tumor. PEB specimens were also collected from five healthy subjects. PEB samples and tumor tissue were examined for hypermethylation of p16^INK4a (CDKN2) gene promoter CpG islands (assayed by methylation-specific PCR) and UT5085 tetranucleotide microsatellite instability (assayed by GeneScan analysis). PEB samples were also subjected to cytologic analysis.

Results: Eight of 33 (24%) tumors exhibited a bandshift at UT5085, and 14 of 33 (42%) exhibited hypermethylation at the p16 promoter. Overall, 17 of 33 (52%) patients had at least one of the two markers in their tumor. Cytologic analysis of PEB samples revealed tumor in 4 of 33 (12%) patients; cytologic findings were normal in all five control subjects. Molecular analysis of PEB samples revealed tumor DNA in 13 of 17 (76%) patients with at least one of the two molecular markers in their tumor. Eight of 14 (57%) patients with p16 hypermethylation in their tumor and 8 of 8 (100%) patients with UT5085 microsatellite instability in their tumor had similar findings in the PEB samples. None of the PEB samples from the control subjects or patients with neither molecular marker in their tumor displayed abnormality.

Conclusion: Molecular analysis of PEB samples holds promise for the early detection of early-stage laryngopharyngeal SCCs. New molecular markers need to be identified to increase the sensitivity of molecular screening.

Key Words: Genetic markers • Microsatellite repeats • Cytodiagnosis • Methylation-specific PCR • p16