Genetic alterations between primary head and neck squamous cell carcinoma and recurrence after radiotherapy : recurrence, genetically related cancer, or second primary?

BACKGROUND: In the attempt to characterize the genetic bases of recurrent head and neck squamous cell carcinoma (HNSCC) after radiotherapy (RT), the authors compared the molecular profiles of primary tumors and recurrences. METHODS: TP53 gene status and instability at 10 microsatellite markers were determined in pre-RT lesions and corresponding local recurrences in a series of 16 HNSCCs. RESULTS: Eight (50%) HNSCCs showed both TP53 and microsatellite instability (MSI) status concordance in pre- and postirradiation biopsies; 3 (18.7%) showed discordance of both TP53 and MSI status; and finally 5 (31.2%) had discordance at only I genetic test. Accordingly, the authors interpreted as true recurrence the 8 concordant cases, and as true second primary malignancies the 3 discordant ones. In the remaining 5 cases with partial DNA correspondence, the exact nature of the new lesion only partially related to the original cancer is a matter of discussion. Patients showing the same mutations among pre- and post-RT HNSCCs had a longer disease-free interval (DFI) and better survival than those showing discordant genetic features (log-rank test, P = .0045). CONCLUSIONS: Post-RT recurrent HNSCCs are genetically heterogeneous. The genetic characterization of the recurrence, especially in those cases with a particularly short DFI showing partially discordant mutations, might have a useful clinical relevance in the restaging process