The origins of multiple squamous cell carcinomas in the aerodigestive tract

BACKGROUND, Chemoprevention and cessation of smoking and alcohol may preven t development of multiple rumors (MTs) in the aerodigestive tract if new MT s arise independently, but they are of no benefit if MTs are due to migrati on of an already transformed clone of tumor cells. This issue was addressed in this study by investigation of the clonality among MTs. METHODS. Mutation analysis of the entire coding region of p53 and loss of h eterozygosity (LOH) pattern analysis of microsatellite markers on chromosom e arms 3p, 9p, and 17p are promising for the investigation of clonality. In the first part of this study, the authors established the variability and stability of these clonal markers by comparing primary head and neck squamo us cell carcinomas (HNSCCs) with their metastases. In the second part of th is study, the authors evaluated nine patients with multiple HNSCCs using th ese markers. In the final part, the authors illustrate the use of these clo nal markers in 11 patients for whom there was diagnostic uncertainty as to whether their second squamous cell carcinoma was either a new primary tumor , a metastasis, or a recurrence. RESULTS. Both p53 gene mutations and LOH patterns were stable during tumor progression. Furthermore, the variability of p53 gene mutations was high. M ore than 90% of the rumors contained a p53 mutation. A particular mutation never occurred more than twice in a total of 69 primary HNSCCs. Five of 69 cases presented a common mutation. In contrast, LOH patterns showed less va riability; they were identical in 5 of 16 cases. The metachronous HNSCCs fr om nine patients all showed different p53 mutations, and in the three cases that were subjected to LOH analysis different patterns were observed. All ii patients for whom there was diagnostic uncertainty about the origin of t heir second squamous cell carcinoma could be categorized as having multiple primary tumors, disseminated disease, or recurrent disease. CONCLUSIONS. Metachronous HNSCCs at different locations are not clonally re lated and thus have not developed from the migration of tumor cells. (C) 20 00 American Cancer Society.