OBJECTIVE: Mutational activation of PIK3CA is associated with poor prognosis in patients with solid tumors, and may predict favorable response to PI3K/AKT/mTOR pathway inhibitors. However, PIK3CA mutational status has not previously been evaluated in patients with cervical carcinoma treated with radical chemoradiotherapy (CRT). The aims of this study were (1) to evaluate the frequency of PIK3CA mutations in patients with cervical cancer treated with radical CRT and (2) to examine the effect of tumor PIK3CA mutational status in pre-treatment biopsies on overall survival (OS) and progression-free survival (PFS). METHODS: Patients with cervical cancer, treated at a single institution with radical CRT, from 1999 to 2008, were eligible for this retrospective study. Pre-treatment tumor biopsies (n=157) were retrieved. Genomic DNA was extracted from tumor blocks, and exons 9 and 20 of the PIK3CA gene were sequenced for mutations. RESULTS: Eighty-two tumors were sequenced for both exon 9 and exon 20. 19/82 (23%) tumors were PIK3CA mutation positive; of these 84% were squamous cell carcinomas. 79% of mutations were in exon 9. PIK3CA mutation status was strongly associated with overall survival (OS) in FIGO stage IB/II patients, unadjusted HR 6.0 (95% CI 2.1-17.5), p=0.0002, but not stage III/IVA patients, unadjusted HR 1.0 (95% CI 0.32-3.1), p=0.98. CONCLUSIONS: In cervical cancer patients treated with CRT, tumor PIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers. Further evaluation with a larger dataset will be required to validate these findings to inform potential clinical trials designs involving PI3K/AKT/mTOR pathway inhibitors.
OBJECTIVE: Mutational activation of PIK3CA is associated with poor prognosis in patients with solid tumors, and may predict favorable response to PI3K/AKT/mTOR pathway inhibitors. However, PIK3CA mutational status has not previously been evaluated in patients with cervical carcinoma treated with radical chemoradiotherapy (CRT). The aims of this study were (1) to evaluate the frequency of PIK3CA mutations in patients with cervical cancer treated with radical CRT and (2) to examine the effect of tumorPIK3CA mutational status in pre-treatment biopsies on overall survival (OS) and progression-free survival (PFS). METHODS:Patients with cervical cancer, treated at a single institution with radical CRT, from 1999 to 2008, were eligible for this retrospective study. Pre-treatment tumor biopsies (n=157) were retrieved. Genomic DNA was extracted from tumor blocks, and exons 9 and 20 of the PIK3CA gene were sequenced for mutations. RESULTS: Eighty-two tumors were sequenced for both exon 9 and exon 20. 19/82 (23%) tumors were PIK3CA mutation positive; of these 84% were squamous cell carcinomas. 79% of mutations were in exon 9. PIK3CA mutation status was strongly associated with overall survival (OS) in FIGO stage IB/II patients, unadjusted HR 6.0 (95% CI 2.1-17.5), p=0.0002, but not stage III/IVApatients, unadjusted HR 1.0 (95% CI 0.32-3.1), p=0.98. CONCLUSIONS: In cervical cancerpatients treated with CRT, tumorPIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers. Further evaluation with a larger dataset will be required to validate these findings to inform potential clinical trials designs involving PI3K/AKT/mTOR pathway inhibitors.
Authors: Matthew M Harkenrider; Merry Jennifer Markham; Don S Dizon; Anuja Jhingran; Ritu Salani; Ramy K Serour; Jean Lynn; Elise C Kohn Journal: J Natl Cancer Inst Date: 2020-11-01 Impact factor: 13.506
Authors: Akinyemi I Ojesina; Lee Lichtenstein; Samuel S Freeman; Chandra Sekhar Pedamallu; Ivan Imaz-Rosshandler; Trevor J Pugh; Andrew D Cherniack; Lauren Ambrogio; Kristian Cibulskis; Bjørn Bertelsen; Sandra Romero-Cordoba; Victor Treviño; Karla Vazquez-Santillan; Alberto Salido Guadarrama; Alexi A Wright; Mara W Rosenberg; Fujiko Duke; Bethany Kaplan; Rui Wang; Elizabeth Nickerson; Heather M Walline; Michael S Lawrence; Chip Stewart; Scott L Carter; Aaron McKenna; Iram P Rodriguez-Sanchez; Magali Espinosa-Castilla; Kathrine Woie; Line Bjorge; Elisabeth Wik; Mari K Halle; Erling A Hoivik; Camilla Krakstad; Nayeli Belem Gabiño; Gabriela Sofia Gómez-Macías; Lezmes D Valdez-Chapa; María Lourdes Garza-Rodríguez; German Maytorena; Jorge Vazquez; Carlos Rodea; Adrian Cravioto; Maria L Cortes; Heidi Greulich; Christopher P Crum; Donna S Neuberg; Alfredo Hidalgo-Miranda; Claudia Rangel Escareno; Lars A Akslen; Thomas E Carey; Olav K Vintermyr; Stacey B Gabriel; Hugo A Barrera-Saldaña; Jorge Melendez-Zajgla; Gad Getz; Helga B Salvesen; Matthew Meyerson Journal: Nature Date: 2013-12-25 Impact factor: 49.962
Authors: Perry W Grigsby; Israel Zighelboim; Matthew A Powell; David G Mutch; Julie K Schwarz Journal: Gynecol Oncol Date: 2013-04-10 Impact factor: 5.482
Authors: Satoru Sagae; Bradley J Monk; Eric Pujade-Lauraine; David K Gaffney; Kailash Narayan; Sang Young Ryu; Mary McCormack; Marie Plante; Antonio Casado; Alexander Reuss; Adriana Chávez-Blanco; Henry Kitchener; Byung-Ho Nam; Anuja Jhingran; Sarah Temkin; Linda Mileshkin; Els Berns; Suzy Scholl; Corinne Doll; Nadeem R Abu-Rustum; Fabrice Lecuru; William Small Journal: Int J Gynecol Cancer Date: 2016-01 Impact factor: 3.437
Authors: Alexi A Wright; Brooke E Howitt; Andrea P Myers; Suzanne E Dahlberg; Emanuele Palescandolo; Paul Van Hummelen; Laura E MacConaill; Melina Shoni; Nikhil Wagle; Robert T Jones; Charles M Quick; Anna Laury; Ingrid T Katz; William C Hahn; Ursula A Matulonis; Michelle S Hirsch Journal: Cancer Date: 2013-08-23 Impact factor: 6.860