Page 249 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
EGFR and PIK3CA mutations in lung cancer patients

in EGFR, particularly in exons 18 to 21, have garnered carcinogenesis. This activation often results from PIK3CA
significant attention for managing NSCLC populations, mutations or the loss of the tumor suppressor phosphatase
serving as predictive markers for favorable responses to and tensin homolog, driving tumor cell growth and
TKIs. 24,25 Among these mutations, the Ex19del and L858R survival. Notably, somatic PIK3CA-activation mutations
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mutations have been identified as the cornerstones for are found in 2 – 7% of NSCLC cases, with a higher prevalence
developing efficient targeted therapies. 3,12,13 in squamous cell carcinoma (7%) than adenocarcinoma
Through direct sequencing, our study uncovered (2%). 30,31 In contrast, our study specifically detected
EGFR tyrosine kinase domain mutations in 41.7% of the PIK3CA mutation in adenocarcinomas more frequently
NSCLC specimens analyzed. Various genetic mutations than in squamous cell carcinoma cases, with a mutational
were identified within our cohort, showcasing the rate of 8.3%, predominantly in Stages II (11.3%) and III
diverse mutational profile of EGFR in our population, (10.5%) compared to early stages (6.3%). In addition, these
with the L858R and Exdel19 mutations being the most mutations were commonly found in elderly patients, in
prevalent. Accordingly, some Moroccan studies, such as both men and women, in agreement with widely reported
those by Boukansa et al., reported an EGFR mutation data indicating that PIK3CA mutations are generally not
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frequency of 23.5%, predominantly involving L858R and gender-associated. Similarly, Zhang et al. reported no
del19 (81.69%). Similarly, Sow et al. identified EGFR significant association between PIK3CA mutations and sex,
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mutations in 21.9% of adenocarcinoma cases, with age, distant metastasis, or smoking status. Furthermore, a
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deletions in exon 19 (65.8%) and L858R mutations (17.8%) recent meta-analysis published by Wang et al. found no
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being the most common. Morjani et al. also documented significant correlation between the mutational profile of
EGFR aberrations in 22.34% of patients, with del19 and PIK3CA and clinicopathological features, including age,
L858R as the most prevalent alterations. sex, smoking status, TNM stage, or lymph node metastasis.
Extensive epidemiological and experimental studies A key observation is that PIK3CA mutations in the
have recently confirmed that EGFR-activating mutations NSCLC population occur at two hotspots: the helical
are frequently associated with specific clinicopathological binding region (exon 9; E542K or E545K) and the catalytic
parameters, including adenocarcinoma histology, female domain (exon 20; H1047L or H1047P). These aberrations
gender, and a history of smoking in various solid tumors, stimulate the catalytic activity of p110α, driving continuous
including LC. 28,29 In contrast, in our cohort, EGFR mutations activation of the PI3K signaling pathway. 31,35,36 These genetic
were found in both male and female individuals, across alterations are classified as oncogenic and targetable, with
young and elderly patients, with no significant difference the E545K mutation being the most frequent, found in
in terms of smoking status, clinical staging, or histological 10.5% of NSCLC patients. 37,38
types. This non-significant finding may be attributed to the In the present study, concomitant PIK3CA and EGFR
limited sample size in our cohort. The presence of EGFR alterations were identified in 3.33% of cases. Extensive
alterations across all stages suggests the possibility of epidemiological and experimental studies confirmed that
treating LC patients with TKIs, regardless of the stage. This the co-existence of PIK3CA mutations with other oncogenic
highlights the potential for identifying EGFR mutations mutations can contribute to EGFR-TKI resistance, 10,20,39
in both treatment-naïve patients and those in later stages, highlighting the need for molecular profiling of PIK3CA
underscoring the importance of molecular profiling across when administering TKIs for LC treatment.
all stages of the disease.
The HER2 gene is a reference oncogene that belongs
Interestingly, based on the ADAURA trial, patients with to the ErbB receptor tyrosine kinase family, which drives
early-stage NSCLC harboring EGFR exon 19 deletions and cellular proliferation through the PI3K–AKT and methyl
EGFR L858R mutations may benefit from Osimertinib, ethyl ketone–ERK signaling cascades. 16,17,40,41 In the current
which has been proven to be more effective than standard study, no HER2 mutations were observed in our cohort.
EGFR TKIs and is associated with longer disease-free Our findings are consistent with those reported by Morjani
survival. These findings emphasize the critical role of et al., who also found an absence of HER2 mutations
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incorporating molecular testing for EGFR into routine in another Moroccan population with LC. Similarly, a
clinical practice, as it is essential to optimize treatment separate Moroccan cohort of 88 patients with advanced
strategies for NSCLC, even in its early stages. lung adenocarcinoma, including 57 men and 31 women,
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With regard to optimizing molecular diagnostics identified a HER2 mutation in only one patient (1.1%).
for NSCLC, it is important to highlight the role of the Worldwide, HER2 mutations are recognized as oncogenic
PI3K/AKT/mechanistic target of the rapamycin signaling in approximately 1 – 3% of NSCLC cases, 17,43 suggesting
cascade, which is frequently activated during lung that these mutations are rare and may be influenced

Volume 9 Issue 1 (2025) 241 doi: 10.36922/ejmo.7111