Tony K H Chung1, Tak Hong Cheung1, So Fan Yim1, Mei Yun Yu2, Rossa W K Chiu3, Keith W K Lo1, Ida P C Lee1, Raymond R Y Wong1, Kitty K M Lau1, Vivian W Wang4, Michael J Worley5, Kevin M Elias5, Stephen J Fiascone5, David I Smith6, Ross S Berkowitz7, Yick Fu Wong8. 1. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong. 2. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong. 3. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong. 4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA. 5. Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA. 6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA. Electronic address: David.Smith@mayo.edu. 7. Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA. Electronic address: Ross_Berkowitz@DFCI.harvard.edu. 8. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong; Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA. Electronic address: yickfuwong@cuhk.edu.hk.
Abstract
INTRODUCTION: Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. METHODS: One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. RESULTS: PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). CONCLUSIONS: As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.
INTRODUCTION:Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. METHODS: One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. RESULTS:PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). CONCLUSIONS: As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.