Microsatellite analysis and response to chemotherapy in head-and-neck squamous-cell carcinoma

Molecular studies have revealed that microsatellite instability and loss of heterozygosity occurred in head-and-neck cancer, suggesting the involvemen t both of suppressor and of mutator pathways in head-and-neck carcinogenesi s. There is evidence for relations between tumor phenotype and clinical par ameters. Indeed, replication-error phenotype, characterized by microsatelli te instability, was associated with decreased sensitivity to chemotherapeut ic agents in cell lines. Loss of heterozygosity is a frequent mechanism of inactivation of tumor-suppressor genes, which might be implicated in resist ance to chemotherapy. In head-and-neck cancer, chemosensitivity is inconsta nt, and no marker is available to predict response to treatment. In order t o evaluate the role of tumor phenotype on resistance to chemotherapy, we an alyzed 56 primary head-and-neck squamous-cell carcinomas collected at time of diagnosis and a sub-group of 23 resistant tumors collected after chemoth erapy at 22 microsatellite loci. At time of diagnosis, only one tumor showe d MSI-H phenotype. Loss of heterozygosity (LOH) was observed in 75% of tumo rs, indicating the dominant role of the suppressor in comparison with the m utator pathway in HNSCC carcinogenesis. No change in microsatellite pattern s was observed after treatment, suggesting that chemotherapy did not select mismatch-repair-deficient clones. Univariate analyses showed that LOH at 9 p or 17p was significantly associated with drug resistance. In a multivaria te analysis, only LOH at 17p remains predictive of low response to chemothe rapy, with a relative risk of 3.7 and 95% CI of 1.1-13, indicating that p53 alterations could play a role in chemotherapy resistance in HNSCC. Int. J. Cancer (Pred. Oncol.) 84:410-415, 1999. (C) 1999 Wiley-Liss, Inc.