EPIDERMAL GROWTH FACTOR RECEPTOR
MUTATION STATUS: DOES YOUNGER
MEAN MORE FREQUENTLY MUTATED?
Wójcik P1, Krawczyk P2, Chorostowska-Wynimko J3, Reszka K4, Duk K3, Muszczyńska-Bernhard B5,
Pankowski J6, Wojas-Krawczyk K2, Czyżewicz G7, Ramlau R8, Skoczek M7, Grenda A2,*,
Orłowski T3, Grodzki T9, Piwowar M10, Roszkowski-Śliż K3, Milanowski J2
*Corresponding Author: Anna Grenda, Ph.D., Department of Pneumonology, Oncology and Allergology, Medical University
of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland. Tel./Fax: +48-81-724-42-93. E-mail: an.grenda@gmail.com
page: 89
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Abstract
Dear Editor,
The median patients’ age at diagnosis of non-smallcell
lung carcinoma (NSCLC), is 65 years. The majority
of advanced NSCLC patients require molecular diagnosis
of tumor tissue for qualification to molecularly targeted
therapies [tyrosine kinase inhibitors of epidermal growth
factor receptor (EGFR), ALK or ROS1]. The molecular
background of NSCLC in different age groups (especially
in the youngest and the oldest groups) is poorly studied.
Recent data have suggested that EGFR mutations are associated
with an older age at diagnosis (adenocarcinoma
female patients of Asian origin) [1]. However, in small
retrospective studies, a higher incidence of EGFR mutations
in young patients has also been suggested [2-4].
More recent studies have suggested that age may not be
as significant predictor of EGFR mutations status [4-6].
In this commentary, we will attempt to prove that
EGFR mutation status in NSCLC is highly dependent on
the patients’ age. Our study enrolled the largest group of
homogenous Caucasian NSCLC patients tested for EGFR
mutations.
The studied group consisted of 12651 NSCLC patients
(median age: 66 ± 7.5 years, range: 25-92 years) and
included 94.3% of adenocarcinoma, 5.3% of not otherwise
specified NSCLC, 0.3% of large cell carcinoma, <0.1%
of adenosquamous carcinoma and <0.1% of squamous
cell carcinoma patients. Patients were divided into 11 age
groups (every 5 years). Routine diagnostics of EGFR status
was performed with molecular probes for a real-time polymerase
chain reaction (PCR) technique on a Cobas z480
(Roche Diagnostics AG, Basel, Switzerland) instrument.
The EGFR gene mutations were detected in 1109
patients (8.77%), including 573 exon 19 deletions (4.53%),
358 L858R substitutions (2.83%) and 178 rare or double
mutations (1.41%). The EGFR gene mutations occurred
significantly more frequently in female than in male patients
(14.4 vs. 4.8%; χ2 = 352.5, p <0.00001). In young
patients (25 to <50 years old), the incidence of mutations
was significantly higher (17.26 vs. 8.39%; χ2 = 50.21,
p <0.00001) than in older patients (>50 years old). The
incidence of mutations was 23.4% in young women and
13.9% in older women (χ2 = 19.24, p = 0.000012) and
10.6% in young men and 4.6% in older men (χ2 = 19.29, p
= 0.000011). The differences in EGFR mutation prevalence
in different age groups were caused by the differences in
the frequency of the exon 19 deletion in female (χ2 = 17.46,
p = 0.000029) and male (χ2 = 29.6, p <0.00001) patients.
The frequency of the L858R substitution and rare or double
mutations was similar in the studied age groups in both
genders. Deletion in exon 19 was the dominant mutation in
young men (deletion frequency 74.1%, L858R frequency
7.4%, rare or double mutations frequency 18.5% of all
examined EGFR mutations). In older men and in young
and older women, exon 19 deletion frequency was 51.8, 56.9 and 50.2%, respectively, whereas the incidence of the
L859R substitution was 30.6, 23.1 and 34.9%, respectively.
The incidence of the exon 19 deletion gradually decreased
along with increasing age of male patients. In women,
the prevalence of the exon 19 deletion was highest in the
youngest and the oldest age groups. Thus, clear trends
were not observed for the L858R substitution and rare or
double mutations (Figure 1).
Our results indicate the entity of hereditary molecular
background for development of the exon 19 deletion in
EGFR in young adults [our preliminary next-generation
sequencing (NGS)] results indicate mutations in tumor
suppressor genes, e.g., MSH2). However, smoking behavior
may influence the presence of EGFR gene mutations
in different female age groups. Moreover, diagnostics of
EGFR mutations in young and older patients should be
particularly careful and meticulous (correct sequence of
genetic testing).
Declaration of Interest. The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of this article.
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