Field cancerization: are multiple primary cancers monoclonal or polyclonal?

Second primary cancers are a difficult problem in the upper aerodigestive tract and in several other organ sites. Among patients with early stage head and neck cancers, second primary tumours are a primary cause of death. It has been postulated that such second cancers represent new tumours developing from carcinogen-damaged cells in the same epithelial surface as the original tumour. An alternative hypothesis is that second primary tumours are the result of micrometastatic foci that have migrated from the original primary site or that have floated away and reimplanted in a secondary site. New methods of examining genetic changes in tumours have made it possible to test this hypothesis. Experimental results obtained from analysis of p53 mutations, the inactive X chromosome as a clonal marker, and specific chromosome markers are discussed and analysed. There are contradictions in the data obtained by different assays, but there are also alternative interpretations for some of the experiments that may resolve these apparent contradictions. The strongest evidence shows that second primary cancers contain genetic markers identical to the original tumour. If additional study confirms that many or most second primary cancers are really metastases then a major shift in how we treat patients with epithelial carcinogen-induced cancers is indicated.