Identification of &lt;i&gt;EGFR&lt;/i&gt; Mutations by Immunohistochemistry with &lt;i&gt;EGFR&lt;/i&gt; Mutation–Specific Antibodies in Biopsy and Resection Specimens from Pulmonary Adenocarcinoma

Kim, Chi Hong; Kim, Seung Hoon; Park, Sonya Youngju; Yoo, Jinyoung; Kim, Sung Kyoung; Kim, Hoon Kyo

doi:10.4143/crt.2014.118

Cited by 31 publications

(38 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although EGFR mutation was a promising predictor of response to EGFR-TKIs treatment, many unfavorable conditions limited its usage. At present, some attempts have been taken to replace tissue specimens with blood, pleural effusion or other substitute samples that may contain tumor information for the detection of EGFR mutations (13,15,30). However, a more constructive attempt is to establish a new predictor system using proteomic techniques.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Tang

Wang

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. IntroductionLung cancer remains a common cause of mortalities worldwide, accounting for 1.6 million mortalities in 2012 and ~20% of all cancer mortalities (1). Non-small cell lung cancer (NSCLC) is the predominant type of the disease with ~80% of cases (1). In the last decade, the important discovery of mutations in the epidermal growth factor receptor (EGFR) gene had led to the development of targeted therapy and personalized medicine (2). One class of anti-tumor drugs that target EGFR is a group of small molecule inhibitors that inhibit the tyrosine kinase domain of EGFR, EGFR-tyrosine kinase inhibitors (TKIs). Examples of EGFR-TKIs include gefitinib and erlotinib (3,4).EGFR-TKIs have demonstrated initial success in some patients with activating mutations (5). However, numerous patients do not respond to the drug (6-8). Therefore, the identification of biomarkers that are predicative of response to the drug became a key issue for doctors to select the optimal therapy. To date, mutations in the EGFR gene (exon 19 deletion, exon 18 G719X and exon 21 L858R) have been reported to be predictors ...

show abstract

Section: Discussionmentioning

confidence: 99%

“…EGFR gene amplification is also used to identify the cause of acquired resistance to EGFR-TKIs by repeated, real-time biopsy (33,34). However, the difficulty of obtaining tissue samples and the presence of critical laboratory requirements limited the application of EGFR-TKI (13,14,30).…”

Section: Discussionmentioning

confidence: 99%

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Tang

Wang

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…Different antibodies targeting a mutation in EGFR can be used on fixed tissues [ 33 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Nonetheless the sensitivity of these antibodies is globally lower than MB methods, in particular those for detection of deletion in exon 19, and their specificity depends on the clone and the mutation for consideration [ 47 , 53 ].…”

Section: The Therapeutic Targets Identified By Immunohistochemistrmentioning

confidence: 99%

Any Place for Immunohistochemistry within the Predictive Biomarkers of Treatment in Lung Cancer Patients?

Hofman

Lassalle

Bence

et al. 2018

Cancers

View full text Add to dashboard Cite

The identification of certain genomic alterations (EGFR, ALK, ROS1, BRAF) or immunological markers (PD-L1) in tissues or cells has led to targeted treatment for patients presenting with late stage or metastatic lung cancer. These biomarkers can be detected by immunohistochemistry (IHC) and/or by molecular biology (MB) techniques. These approaches are often complementary but depending on, the quantity and quality of the biological material, the urgency to get the results, the access to technological platforms, the financial resources and the expertise of the team, the choice of the approach can be questioned. The possibility of detecting simultaneously several molecular targets, and of analyzing the degree of tumor mutation burden and of the micro-satellite instability, as well as the recent requirement to quantify the expression of PD-L1 in tumor cells, has led to case by case development of algorithms and international recommendations, which depend on the quality and quantity of biological samples. This review will highlight the different predictive biomarkers detected by IHC for treatment of lung cancer as well as the present advantages and limitations of this approach. A number of perspectives will be considered.

show abstract

“…Two novel antibodies against EGFR-mutated proteins were developed recently. SP111 is specific for delE746-A750 and SP125 for the L858R mutation; both SP111 and SP125 show an efficacy similar to that of the original clone ( 27 – 29 ). To date, no study has assessed the utility of SP111 or SP125 for cytological specimens.…”

Section: Introductionmentioning

confidence: 99%

Detection of epidermal growth factor receptor mutations in lung adenocarcinoma cytological specimens by immunocytochemistry

et al. 2017

View full text Add to dashboard Cite

Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR) improve the survival of patients with lung adenocarcinoma, and determine the EGFR mutation status before treatment is necessary. In contrast to biopsy samples, cytological specimens are obtained less invasively and are useful for EGFR mutation analyses. Recently, novel antibodies against two major EGFR mutations were developed: SP111, which is specific for the E746-A750 deletion in exon 19; and SP125, which is specific for the L858R mutation. To the best of our knowledge, no study has evaluated cytological specimens using the two novel antibodies, thus their specificity and sensitivity were examined in surgical resection, and cytological lung adenocarcinoma samples in the present study. Previous screening for EGFR mutation status by molecular testing identified delE746-A750 in 3 cases and the L858R mutation in 7 cases; the other cases did not have the L858R or the delE746-A750 mutation. Using a four-grade scoring system (score 0 to 3+), the immunohistochemistry (IHC) and immunocytochemistry (ICC) results were compared with those of molecular testing. Using a score of ≥2 as positive, IHC and ICC using SP111 demonstrated sensitivities of 100 and 33.3%, and specificities of 100 and 100%, respectively. IHC and ICC using SP125 revealed sensitivities of 100 and 71.4%, and specificities of 100 and 100%, respectively. Therefore, screening for EGFR mutations by ICC may facilitate therapeutic decision-making, particularly in medical centers that are unable to perform molecular testing.

show abstract

Identification of <i>EGFR</i> Mutations by Immunohistochemistry with <i>EGFR</i> Mutation–Specific Antibodies in Biopsy and Resection Specimens from Pulmonary Adenocarcinoma

Cited by 31 publications

References 20 publications

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Any Place for Immunohistochemistry within the Predictive Biomarkers of Treatment in Lung Cancer Patients?

Detection of epidermal growth factor receptor mutations in lung adenocarcinoma cytological specimens by immunocytochemistry

Contact Info

Product

Resources

About