Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer.

摘要: Background Thymidylate synthase (TS), an essential enzyme in DNA synthesis, is a target for the fluoropyrimidines, important group of antineoplastic agents used widely treatment head and neck cancer. Purpose We evaluated relationships between level and/or pattern tumor TS expression response to fluorouracil (5-FU)-based neoadjuvant chemotherapy patients with advanced Methods Tumor specimens from 86 were available this retrospective analysis. The enrolled four consecutive phase II studies that tested combinations 5-FU, leucovorin, cisplatin or without added methotrexate plus piritrexim interferon alfa-2b (IFN alpha-2b). protein tumors was assessed by use 106 monoclonal antibody standard immunohistochemical staining techniques. immunostaining classified according its intensity (TS 0-1 = low, 2 intermediate, 3 high) extent (focal less than 25% cells positive; diffuse greater equal positive). Data 79 analysis patient/tumor characteristics; 70 assessable their chemotherapy. Results There statistically significant association degree differentiation; higher proportion whose exhibited had undifferentiated poorly differentiated (P .04, Jonckheere-Terpstra trend test). Among who chemotherapy, associated lower rate complete (i.e., disappearance clinically detectable disease minimum 4 weeks time initial determination) immunostaining, but not .09, exact test); among 39 treated regimens included cisplatin, IFN alpha-2b, inverse .02, overall survival found be associated. Patients exhibiting focal have experienced significantly longer pattern; 53 median 24.7 months, whereas has yet been reached 22 two-tailed logrank However, advantage versus limited also intensity. Conclusions implications Characterization may value identifying cancer would benefit fluoropyrimidine-based