Persistence of genetically altered fields in head and neck cancer patients: Biological and clinical implications

In 1953, Slaughter et al, [D, P, Slaughter et al,, Cancer (Phila,), 6: 963- 968, 1953] proposed the concept of field cancerization in patients with squ amous cell carcinoma of the head and neck (HNSCC) and discussed its clinica l significance for the development of second primary tumors and local recur rences. To define the process of field cancerization and its putative clini cal implications, we analyzed genetic aberrations in HNSCC and the accompan ying macroscopically normal mucosa, In 28 HNSCC patients, loss of heterozyg osity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p, For patients who showed l oss of heterozygosity in their mucosal biopsies, all margins of the surgica l specimen were subsequently analyzed to determine the extension of the fie ld, In these cases, additional markers at 8p, 13q, and 18q as well as p53 m utations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the H NSCC patients. The field varied in size between patients and consisted of g enetically different subclones, In 7 of 10 cases, the field extended into t he surgical margins. One particular patient with a genetically altered fiel d in a surgical margin developed a local recurrence after 28 months of foll ow-up. Microsatellite analysis showed that this recurrence had more molecul ar markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed furthe r into a new malignancy, Our data show that genetically altered mucosa rema ins after treatment in a significant proportion of HNSCC patients, which ma y explain in part the high frequency of local recurrences and second primar y tumors, Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management .