EGFR mutation testing, from bench to practice: A single Irish institute experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19064-e19064
Author(s):  
Hassan Shikhrakab ◽  
Cathal O'Brien ◽  
Nemer Osman ◽  
Kenneth John O'Byrne
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Egfr Gene ◽  
Exon 19 Deletion ◽  
Exon 20 ◽  
Treatment Intent ◽  
Exon 19

e19064 Background: Epidermal growth factor receptor (EGFR) gene mutations determine the treatment and prognosis in lung adenocarcinoma. Exon 19 and exon 21 (L858R) deletions represent the most common recognised mutations detected. To date, no figures regarding the prevalence of EGFR mutations in the Irish population have been published. Methods: The prevalence of EGFR mutations was retrospectively analysed for all patient samples tested since the introduction of EGFR testing routinely (Mar to Dec 2012) in a single Irish institute. The presence of 41 known treatment linked EGFR mutations in exons 18, 19, 20 and 21 of the EGFR gene was tested in 209 Irish patients. Resection, core biopsy or FNA samples were analysed using a commercially available CE-IVD marked multiplex real-time PCR assay. Samples were included from patients of curative and palliative treatment intent. Results: 30 out of 209 patients with lung adenocarcinoma tested had an EGFR mutation (13%, 95% CI 8.4-17.6%). Of the mutations detected relative frequency was as follows: exon 19 deletion 63.3% (n=19, 95% CI 46.1-80.6%), exon 21 (p.L858R) 16.7% (n=5, 95% CI 3.3-30.0%), exon 20 insertions 13.3% (n=4, 95% CI 1.2-25.5%) and exon 18 (p.G719X) and exon 20 (p.T790M) both at 3.3% (n=1, 95% CI 0-9.8%). Of those patients tested 51.2% were male (n=107) and 48.8% (n=102) female. The incidence of mutations was higher in females than in males; 63.3% of those with an EGFR mutation were female (n=19, 95% CI 46.1-80.6%). Reciprocally, the male percentage was 36.7% (n=11, 95% CI 19.4-53.9). The mean age at testing was 67 years. Complete smoking data was unavailable for this study. All samples tested were formalin fixed paraffin embedded tissue or cell preparations. Turn around time (TAT) for EGFR mutation processing substantially improved over ten month period, from over five weeks to less than four working days. Conclusions: This group of patients represent the largest cohort of patients tested for EGFR mutation in a single institute in Ireland in less than 12 months. The incidence of EGFR mutations in this patient population is comparable to current European estimates. The gender bias was notable amongst those tested, with female patients being nearly twice as likely to harbour an EGFR mutation.

Prognostic implication of the EGFR gene mutations in a large cohort of Japanese patients with early stage lung adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7574-7574 ◽  
Author(s):  
T. Kosaka ◽  
Y. Yatabe ◽  
R. Onozato ◽  
T. Mitsudomi
Keyword(s):  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Prognostic Impact ◽  
Egfr Gene ◽  
Deletion Mutations ◽  
Exon 19 Deletion ◽  
Never Smokers ◽  
Exon 19

7574 Background: Prognostic impact of epidermal growth factor receptor (EGFR) gene mutations in lung adenocarcinoma remains controversial. We examined a large cohort of lung adenocarcinoma resected in a single institution for EGFR mutations and evaluated its prognostic implication. Methods: We analyzed 402 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection at our department, from May 2000 through December 2005. Total RNA was extracted and direct sequencing of exons 18–21 of EGFR gene was performed after reverse transcription - polymerase chain reaction. KRAS and TP53 gene mutations were also analyzed in 209 adenocarcinoma patients from this cohort. Results: We found that 196 patients (49%) had EGFR mutations. Of them, exon 19 deletion mutations were 83 (42%) and L858R mutations were 92 (47%). EGFR mutations were significantly frequent in female (P<0.0001), never smokers (P<0.0001), and well to moderately differentiated adenocarcinoma (P<0.0001). In 347 patients who were not treated with gefitinib, prognostic effect of EGFR mutations was evaluated. Patients with EGFR mutations survived for a longer period than those without the mutations after surgery in univariate analysis (P=0.0046, log rank test). We did not detect any difference in overall survival between the patients with exon 19 deletion mutations and those with L858R mutations (P=0.3962). There were tendencies that patients with KRAS mutations or TP53 mutations survived for a shorter period than those without mutations, although there was no statistical significance (P=0.2534 and 0.0859). Multivariate analysis using the Cox proportional hazards model revealed that never smokers (P=0.0253) and disease stage (P<0.0001) were independent prognostic factors. However, all gene mutations were not independent prognostic factors (EGFR; P=0.4763, KRAS; P=0.7998, TP53; P=0.3464). Conclusion: EGFR mutations were not independently associated with prognosis of patients with early stage adenocarcinoma of the lung. Furthermore, there was no difference between exon 19 deletion mutations and L858R mutations in their prognostic impact. No significant financial relationships to disclose.

Novel mutations and mutation pattern of epidermal growth factor receptor (EGFR) gene in Chinese patients with primary lung adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7667-7667
Author(s):  
T. Mok ◽  
P. Lui ◽  
K. C. Lam ◽  
A. Yim ◽  
I. Wan ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Egfr Mutation ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Novel Mutations ◽  
Egfr Gene ◽  
Mutation Pattern ◽  
Exon 20 ◽  
Egfr Tki ◽  
Exon 19

7667 Background: EGFR mutation is a diverse and complex phenomenon. Shigematsu et al (JNCI 97:339,2005), analyzing NSCLC samples from multiple ethnicities and histologic cell types, reported 11 types of in-frame deletions in exon 19 (46%), 9 missense mutation in exons 18, 20, 21 (45%) and 8 in-frame insertion in exons 20 (9%). 3/130 tumors (2.3%) had multiple mutations. Here we report the incidence, mutation pattern and novel finding of EGFR mutation in a homogenous ethnic group with adenocarcinoma of lung. Methods: Between 2004 and 2006 we isolated genomic DNA from 194 (archival 53, prospective 141) primary lung adenocarinoma for PCR amplification of EGFR exon 18–21. We isolated tumor cell by micro-dissection. PCR products were purified and sequenced using the BigDye Terminator Cycly Sequencing Ready Reaction Kit (Applied Biosystem) and run on Applied Biosystem 3100 Genetic Analyzer. Results: We found 79 EGFR mutations in 73 tumors (37.6%). Six (8.2%) had double mutations. IN-FRAME DEL: 10 types in exon 19 (39 cases, 49.4%); 1 type in exon 18 (1 case). MISSENSE MUTATION: 2 types in exon 18 (2 cases); 4 types in exon 20 (5 cases) and 2 types in exon 21 (29 cases, 36.7%) IN-FRAME INSERTION: 3 types in exon 20 (3 cases). Typical exon 19 E746-A750del and exon 21 L858R mutations accounted for 31% and 34%, respectively. We found 11 types of mutations not previously described.( Table ) Four pts with novel mutations received EGFR TKI and 3 attained PR (all with exon 19 del). Two pts have T790M mutations without prior exposure to EGFR TKI and both with double mutations. Conclusion: Mutation pattern of EGFR gene in Chinese pts with adenocarcinoma is similar to the Shigematsu report. The overall incidence of EGFR mutation and multiple mutations are higher but in-frame insertion in exon 20 is less common. Majority of the novel mutations are rare mutations involving exon 18 and 20. No significant financial relationships to disclose. [Table: see text]

iTARGET: A phase II trial to assess the response to gefitinib in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7504-7504 ◽  
Author(s):  
L. V. Sequist ◽  
R. G. Martins ◽  
D. Spigel ◽  
S. M. Grunberg ◽  
P. A. Jänne ◽  
...  
Keyword(s):  
Copy Number ◽  
Egfr Mutation ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Direct Dna Sequencing ◽  
Exon 20 ◽  
Exon 19

7504 Background: Somatic EGFR mutations correlate with increased response and survival in NSCLC patients (pts) treated with gefitinib. We conducted the 1st prospective US trial of 1st-line gefitinib in pts with advanced NSCLC harboring EGFR mutations. Methods: Chemotherapy-naïve pts with stage IIIB with effusion or IV NSCLC, measurable disease, and = 1 characteristic associated with mutations (female (F), adenocarcinoma (AC), never-smoking (NS), East Asian (EA)) underwent direct DNA sequencing of tumor tissue EGFR exons 18–24. Mutation-positive pts received gefitinib (250 mg/d) until progression or unacceptable toxicity. The primary outcome was response rate (RR) by RECIST criteria. Results: We sequenced 98 pts and detected EGFR mutations in 34 (35%); 3 were not assessable. Observed mutations were 18 (53%) exon 19 deletions (del), 9 (26%) L858R, 3 (9%) exon 20 insertions (ins), 2 T790M/L858R, 1 G719A, and 1 L861Q. Characteristics of the 98 screened pts were 69 F, 89 AC, 37 NS, and 5 EA; those of the 34 mutation pts were 20 (59%) F, 31 (91%) AC, 19 (56%) NS and 2 (6%) EA. The best predictor of EGFR mutation was NS. Of the 34 mutation pts, 31 (91%) received gefinitib. Reasons for non-treatment were pt preference (1 exon 19 del) and mutation associated with gefitinib-resistance (1 T790M/L858R, 1 exon 20 ins). Adverse events were mainly grade 1–2 rash and diarrhea; 1 case of grade 4 interstitial lung disease occurred after 2 weeks of therapy. The RR was 58% (95% confidence interval 39–75) and was 78% in L858R pts and 65% in del 19 pts. There were no responses among the G719A, L861Q, T790M/L858R and exon 20 ins pts treated. 12 pts have progressed, 18 remain on therapy. The median progression-free survival (PFS) is currently 11.8 mo and does not differ by mutation type, though follow-up is short (median 6.8 mo, range 1–24). 27 pts are still alive. Of the 31 pts treated, 22 (71%) had high EGFR gene copy number (amplification (3) or high polysomy (19)); RR and PFS did not vary by copy number. Conclusions: 1st-line gefitinib therapy in EGFR mutation-positive NSCLC pts is feasible in a multi-institutional study, well tolerated, and yields a substantial RR and PFS. This strategy should be compared to standard chemotherapy in a genotype-directed randomized trial. No significant financial relationships to disclose.

Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

2021 ◽  
pp. 030089162110055
Author(s):  
Dashi Zhao ◽  
Jun Fan ◽  
Li Peng ◽  
Bo Huang ◽  
Yili Zhu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma ◽  
Sporadic Cases ◽  
Epidermal Growth ◽  
Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

Immunohistochemistry Profile Predicts EGFR Mutation Status in Lung Adenocarcinoma

2020 ◽  
Vol 28 (5) ◽  
pp. 502-506
Author(s):  
Wencheng Li ◽  
Angela G. Niehaus ◽  
Stacey S. O’Neill
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Mutation Status ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Napsin A ◽  
Therapeutic Decisions

Significant advances in targeted therapy have been made in recent years for patients with lung adenocarcinoma. These targeted therapies have made molecular testing of paramount importance to drive therapeutic decisions. Material for testing is often limited, particularly in cytology specimens and small core biopsies. A reliable screening tool is invaluable in triaging limited tissue and selection for epidermal growth factor receptor ( EGFR) mutation testing. We hypothesized that the immunohistochemistry (IHC) profile of lung adenocarcinoma predicts EGFR mutation status. In this retrospective study, we evaluated the thyroid transcription factor-1 (TTF-1)/napsin A IHC profile and EGFR mutation status in 339 lung adenocarcinomas at our academic institution. In our cohort, we found that 92.3% of cases were positive for TTF-1 and/or napsin A by IHC with an EGFR positivity rate of 17.3%. Importantly, 7.7% of the cases were dual TTF-1/napsin A negative, and none of these cases contained EGFR mutations. This finding supports the use of TTF-1 and napsin A IHC to identify cases where EGFR mutation status will be negative, thus preserving limited tissue for other ancillary testing.

scholarly journals Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 93-96 ◽  
Author(s):  
Jiang Rong ◽  
Ma Chunhua ◽  
Lv Yuan ◽  
Mu Ning ◽  
Li Jinduo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lung Adenocarcinoma ◽  
Gene Mutation ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Egfr Gene ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Egfr Gene Mutation

AbstractObjectiveTo discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.Methods5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid.Results5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method.ConclusionARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

scholarly journals Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival

2014 ◽  
Vol 48 (2) ◽  
pp. 173-183 ◽  
Author(s):  
Karmen Stanic ◽  
Matjaz Zwitter ◽  
Nina Turnsek Hitij ◽  
Izidor Kern ◽  
Aleksander Sadikov ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Lung Adenocarcinoma ◽  
Cumulative Incidence ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Mutation Status ◽  
Course Of Disease ◽  
Epidermal Growth ◽  
Egfr Mutant

AbstractBackground. The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methods. We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.Results. Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.Conclusions. Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

Validation study of direct sequencing and PCR-invader for detecting EGFR mutations in non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8094-8094
Author(s):  
Y. Naito ◽  
K. Goto ◽  
H. Kenmotsu ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Direct Sequencing ◽  
Pcr Amplification ◽  
The Other ◽  
Egfr Mutations ◽  
Wild Type ◽  
Highly Sensitive ◽  
Formalin Fixed Paraffin Embedded ◽  
Exon 19 Deletion ◽  
Exon 19

8094 Background: EGFR mutation is both a predictive and prognostic factor for NSCLC treated with EGFR-TKI. Although new, highly sensitive methods for detecting EGFR mutations are currently available, these methods have not been validated. Methods: To validate direct sequencing and PCR-invader for detecting EGFR mutation, we analyzed 124 NSCLC by both methods concomitantly. Tumor tissues were obtained by surgical resection. Formalin-fixed paraffin-embedded specimens were prepared to analyze EGFR mutation. In direct sequencing, Exon 18, 19, and 21 of the EGFR gene were amplified, and PCR amplification products were sequenced directly (Mitsubishi Chemical Medience Corporation). PCR-invader was performed using the invasive cleavage of probe oligonucleotides to detect 10 mutations including Exon 18, 19, 20, 21 (BML incorporation). Results: EGFR mutations were detected in 51 patients (41%) by direct sequencing and 56 (45%) by PCR-invader. Discordance between two methods was found in 12 patients (10%). Exon 19 deletion was detected in 18 and 22 patients respectively. Exon 21 L858R was detected in 30 and 32 patients respectively. Each mutation in exon 19 deletions or L858R detected by direct sequencing could also be identified by PCR-invader. Overall 45 mutations were concordant by both methods. In two patients who received gefitinib, one patient with wild type by both methods did not respond to gefitinib. On the other hand, the other patient expressing Exon 19 deletion by PCR-invader but regarded as wild type by direct sequencing responded to gefitinib monotherapy. Conclusions: Discrepancy between two methods for detecting EGFR mutation was demonstrated and PCR-invader seems to be more sensitive. Further investigation including other highly sensitive methods is currently underway. No significant financial relationships to disclose.

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