J Pathol Transl Med.  2022 May;56(3):126-133. 10.4132/jptm.2022.01.04.

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand

• Dechaphunkul A
• Thongwatchara P
• Thongsuksai P
• Dechaphunkul T
• Geater SL

• KMID: 2529803
• DOI: http://doi.org/10.4132/jptm.2022.01.04

Abstract

Background
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC.
Methods
Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations.
Results
The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations.
Conclusions
The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Keyword

mutations; Head and neck squamous cell carcinoma; Oral cavity carcinoma; Hypopharyngeal carcinoma; Oropharyngeal carcinoma

Figure

• 

  Fig. 1 PIK3CA mutations in exons 9 and 20 using conventional PCR as illustrated in sequencing chromatograms showing a missense mutation in sample No. PS212 at position 1633, G>A (E545K) in exon 9 (A), a missense mutation in sample No. PS243 at position 3140, A>G (H1047R) in exon 20 (B), and a silent mutation in sample No. PS251/1, C>T (T1025T) in exon 20 (C). PIK-3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PCR, polymerase chain reaction.

• 

  Fig. 2 Amplification plot of allele-specific real-time PCR showing PIK3CA mutations in exon 9 and exon 20 and the HEX (green, wild-type PIK3CA allele) and FAM (blue, mutated PIK3CA allele) signals. (A) A missense mutation in sample No. PS212 at position 1633, G>A (E545K) in exon 9. (B) A missense mutation in sample No. PS243 at position 3140, A>G (H1047R) in exon 20. (C) A silent mutation in sample No. PS251/1, C>T (T1025T) in exon 20. PCR, polymerase chain reaction.

• 

  Fig. 3 Kaplan-Meier survival curves of overall survival for patients with wild-type PIK3CA or mutant PIK3CA. PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.

Reference

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