Abstract 3125
Background
Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers including HNSCC. The presence of mutations have shown to associate with prognosis and might predict response to phosphoinositide 3-kinase (PI3K) inhibitors. However, the frequency of mutations is various among primary tumor locations, so this might be relevant to distinguish the possibility of treatments and outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in patients with oral cavity and hypopharyngeal carcinoma.
Methods
Ninety-six fresh biopsies consisted of 73 oral cavity and 23 pyriform sinus carcinoma were collected for DNA extraction. DNA samples were first investigated to ascertain a reference mutational points in PIK3CA exons 4, 9 and 20. We subsequently designed two probes labelled with two different fluorescent dyes for the wild-type and mutated alleles. Mutational analysis was further carried out by using allele-specific real time PCR.
Results
We identified mutations in 10% of patients (10 out of 96 HNSCC specimens). Among 10 mutant specimens, there were 5 missense mutations (2 samples in exon 9 (E545K) and 3 samples in exon 20 (H1047R)), and 5 silence mutation in exon 20 (T1025T). None of mutation was found in exon 4. Exon 9 mutation was detected in 2 out of 96 cases and was merely from hypopharyngeal carcinoma. In exon 20, 8 mutations were found (2 hypopharyngeal carcinoma and 6 oral cavity carcinoma). Overall frequency of mutations in three exons were 8% and 17% in oral cavity and hypopharyngeal carcinoma, respectively.Table: 1090P
Frequency of PIK3CA mutations in HNSCC
| Location of HNSCC | % PIK3CA mutation | Overall % PIK3CA mutation | ||
|---|---|---|---|---|
| Exon 4 | Exon 9 | Exon 20 | in three exons | |
| Oral cavity carcinoma | 0 (0/61) | 0 (0/73) | 8 (6/73) | 8 (6/73) |
| Hypopharyngeal carcinoma | 0 (0/21) | 8 (2/23) | 8 (2/23) | 17 (4/23) |
| Frequency of mutation | 10 (10/96) |
Conclusions
Our study showed more frequency of PIK3CA mutations in hypopharyngeal carcinoma than oral cavity carcinoma. These results suggest that its mutation may be more involved in the carcinogenesis, and hypopharynx should be primary site of interest for further studies.
Clinical trial identification
Legal entity responsible for the study
Unit of Medical Oncology, Faculty of Medicine, Prince of Songkla University.
Funding
Faculty of Medicine, Prince of Songkla University.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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