We have previously reported that loss of p53 tumor suppressor protein results in centrosome hyperampli®ca-tion, which leads to aberrant mitosis and chromosome instability. Since p53 is either deleted or mutated in human cancers at a high frequency, we investigated whether human cancers showed centrosome hyperampli®cation. Screening of advanced stage breast ductal carcinomas and squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome hyperampli®cation is frequent in both tumor types. Moreover, through the analyses of p53 in SCCHN samples by direct sequencing and by loss-of-heterozygosity test, we found that p53 mutations correlated with occurrence of centrosome hyperampli®cation. However, in some cases, we observed centrosome hyperampli®cation in tumors that retained wild-type p53. These tumors contained high levels of Mdm2. Since Mdm2 can inactivate p53 through physical association, we investigated whether Mdm2 overexpression induced centrosome hyperampli®cation. We found that Mdm2 overexpression, like loss of p53, induced centrosome hyperampli®cation and chromosome instability in cultured cells.

Head and neck cancers comprise a complex genetic disease. Although much has been learned about the molecular genetics of head and neck cancers, continued study of multiple genes is critical for further progress. Gene therapy, although promising, must also overcome this complexity.

Advanced tongue cancer is associated with poor survival despite aggressive therapy. In an attempt at cure, many patients undergo total glossectomy, which significantly affects function and quality of life (QOL). This study was designed to determine the survival rate and QOL of patients who had undergone total glossectomy. A total of 54 patients underwent total glossectomy, with or without total laryngectomy, for advanced tongue cancer from 1970 to 1996. Patient outcomes were assessed for the following: 1. disease-free survival, 2. function, utilizing the Performance Status Scale (PSS), and 3. QOL, using two general cancer questionnaires (FACT-G and EORTC QLQ-C30) and a series of questions specific for head and neck cancer patients. Corrected actuarial survival was 51% and 41% at 3 and 5 years, respectively. Functional assessment using the PSS demonstrated significant deficits in speech and deglutition. QOL questionnaires revealed problems with eating, speaking, socializing, and shoulder function. However, the overall responses demonstrated that these patients have adjusted to their deficits and have a good QOL. It was concluded that total glossectomy, with or without total laryngectomy, can result in meaningful survival and an adequate QOL can be achieved in selected patients.

Background: Salvage surgery is often the only curative option for recurrent cancer. In patients whose initial tumor is stage T3 or T4, the primary therapy often makes salvage even more difficult. We therefore analyzed the outcome in patients who were originally treated for T3 or T4 squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx and who then had a recurrence and chose to undergo further therapy for cure.Patients and Methods: From 1980 to 2000, a total of 940 patients were treated for stage T3 or T4 cancer. Forty-eight patients underwent salvage therapy for recurrence: 24 for primary site recurrence, 20 for regional recurrence, and 4 for locoregional recurrence. Results:The mean time to recurrence was 14.0 months, and the mean survival time was 26.2 months. Among the 28 patients treated for primary site recurrence, the mean time to rerecurrence was 12.6 months, and the mean sur-vival time was 27.3 months. Only 5 of the 28 patients had prolonged survival. The stage of the recurrent disease did not influence outcome. Among the 20 patients treated for neck recurrence, the mean time to recurrence was 14.0 months, and the mean survival time was 25.0 months. Six of the 20 patients had prolonged survival, but none had a recurrence in a previously dissected and irradiated neck.Conclusions: These results show the limited potential for survival in patients who have a recurrence after treatment for advanced primary site head and neck cancer. Patients who have not undergone all modalities of therapy have the potential for salvage, but even then the chances are limited. Given the morbidity of salvage therapy, and the limited chance for cure, physicians must cautiously counsel patients who are contemplating treatment of recurrent cancer after therapy for advanced disease.