PIK3CA mutation and CNV status and post-chemoradiotherapy survival in patients with cervical cancer

Autor: John B. McIntyre, Michelle Dean, Martin Köbel, Tien Phan, Emeka K. Enwere, Elizabeth N. Kornaga, Corinne M. Doll, Prafull Ghatage, Angela Chan, Kevin Martell, Susan P. Lees-Miller
Rok vydání: 2020
Předmět:
Adult
0301 basic medicine
Oncology
medicine.medical_specialty
Adolescent
Class I Phosphatidylinositol 3-Kinases
Gene Dosage
Uterine Cervical Neoplasms
Single Center
Phosphatidylinositol 3-Kinases
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
Humans
Medicine
Digital polymerase chain reaction
neoplasms
Protein kinase B
PI3K/AKT/mTOR pathway
Aged
Neoplasm Staging
Aged
80 and over
Cervical cancer
Univariate analysis
business.industry
Pik3ca mutation
High-Throughput Nucleotide Sequencing
Obstetrics and Gynecology
Chemoradiotherapy
Middle Aged
medicine.disease
Immunohistochemistry
Survival Rate
030104 developmental biology
Tissue Array Analysis
030220 oncology & carcinogenesis
Mutation
Female
business
Proto-Oncogene Proteins c-akt
HeLa Cells
Signal Transduction
Zdroj: Gynecologic Oncology. 158:776-784
ISSN: 0090-8258
DOI: 10.1016/j.ygyno.2020.06.506
Popis: Purpose This study aimed to describe the prognostic value of PI3K/AKT pathway mutations in a large cohort of patients with cervical cancer. Experimental design Patients with pre-treatment archival specimens, diagnosed with FIGO stages IB-IVA cervical cancer between 1998 and 2014 and treated with radical, curative intent chemoradiotherapy (CRT) at a single center were identified. Mutational status was determined by next generation sequencing and PIK3CA copy number (CNV) was assessed by digital PCR. Results 190 patients with available pre-treatment tumor specimens were identified. Median OS and PFS were 57.4 and 46.0 months, respectively. A total of 161 tumors were successfully sequenced; 60 (37.3%) had PI3K/AKT pathway mutations, with 50 (30.1%) having PIK3CA hotspot mutations. PIK3CA CNV gain was noted in 79 (59.2%) of the 154 successfully analyzed. On univariate analysis, PIK3CA mutation was associated with poor OS (HR 1.73; 95% CI: 1.03–2.92; p = .037) but not PFS (HR 1.38; 0.84–2.28; p = .204). Absence of any PI3K/AKT pathway mutation was associated with improved OS (HR 1.68; 1.01–2.81; p = .046) but not PFS (HR 1.50; 0.93–2.43; p = .202). Associations were not maintained when adjusting for clinical factors. On univariate analysis, PIK3CA mutation positive, CNV normal tumors were associated with poorer OS (HR 2.55; 1.18–5.50; p = .017) and trend to worse PFS (HR 1.87; 0.90–3.83; p = .094) when compared to those with CNV gain and wildtype PIK3CA. Conclusions PI3K/AKT pathway mutations are common in cervical cancer. Consideration of PIK3CA mutational status with CNV status may be important in predicting outcome in cervical cancer patients.
Databáze: OpenAIRE
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