Different Prognostic Roles of Mutations in the Helical and Kinase Domains of the PIK3CA Gene in Breast Carcinomas

作者: Mattia Barbareschi , Fiamma Buttitta , Lara Felicioni , Sabrina Cotrupi , Fabio Barassi

DOI: 10.1158/1078-0432.CCR-07-0266

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摘要: Purpose: In breast cancer, the PIK3CA gene is frequently mutated at “hotspots” in exons 9 and 20, corresponding to helical kinase domains, respectively. We decided investigate association of mutations with pathologic features clinical outcome a large series patients cancer. Experimental Design: Frozen samples from 163 consecutive were analyzed for using PCR single-strand conformation polymorphism sequence analyses. Results: identified 46 missense mutations, 24 (53%) exon 9, 21 (47%) 20. Twelve (50%) E542K type 11 (46%) E545K type. Twenty (95%) 20 H1047R substitutions. Mutations more frequent lobular carcinomas (42% cases) than ductal carcinoma (11% cases; P = 0.002). At univariate survival analysis, associated prolonged overall disease-free survival, whereas significantly worse prognosis. multivariate strongest independent factor predict poor prognosis ( 0.0003) 0.001). Conclusion: Our data show that are typical infiltrating carcinomas. addition, they indicate different prognostic value: independently early recurrence death, optimal

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