Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence in situ hybridization methods

Kao, H.; Yeh, Yi Chen; Lin, Chin Hsuan; Hsu, Wei Fang; Hsieh, W.-Y.; Ho, Hsiang‐Ling; Chou, Teh Ying

doi:10.1016/j.lungcan.2016.09.007

Cited by 11 publications

(6 citation statements)

References 39 publications

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“…Real-time PCR was performed using the StepOnePlus™ Real-Time PCR System (Applied Biosystems). The mutation status of a sample was determined by using the parameter described previously [26]. Samples were considered as mutation positive if a specific sigmoid curve was observed with Ct of mutation reaction ≤37 and/or ΔCt value ≤7.…”

Section: Methodsmentioning

confidence: 99%

The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies

Kao

Yeh

et al. 2019

Diagn Pathol

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Background Adenosquamous carcinoma (ADSC) of the lung, a rare but aggressive subtype of non-small cell lung cancer (NSCLC), is defined as a carcinoma containing components of adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). Mutations of epidermal growth factor receptor (EGFR) are found at a frequency of 15 to 44% in Asian ADSC, and EGFR tyrosine kinase inhibitors (EGFR-TKIs) are a more effective treatment for EGFR-mutated ADSC compared to chemotherapy. However, ADSC in small lung biopsies could be misdiagnosed as SqCC or non-small cell carcinoma (NSCC) favor SqCC due to undersampling, which may result in neglecting of EGFR mutation testing and affecting patients’ clinical management, particularly in Asian patients that relatively have high prevalence of EGFR mutation. Methods A total of 148 small lung biopsy cases with pathological diagnosis of SqCC or NSCC favor SqCC were retrospectively enrolled. The frequency of EGFR mutations and the correlation between patients’ EGFR mutation status and clinicopathological characteristics were evaluated. Results EGFR mutations were found in 8.8% (13 /148) of all cases with 5.2% (7/135) in SqCC and 46.2% (6/13) in NSCC favor SqCC. There were 7 (53.8%) L858R mutation, 4 (30.8%) exon 19 deletions, and 2 (15.4%) cases with coexistent L858R and T790 M mutations. Multivariate analysis showed that EGFR mutations were more prevalent in never-smokers (83.3% versus 16.7%, p = 0.006) and patients diagnosed as NSCC favor SqCC (46.2% versus 5.2%, p = 0.001). Moreover, 75% (3/4) of EGFR mutation-positive cases with subsequent surgical resection or rebiopsy were further diagnosed as ADSC. Conclusions EGFR mutation testing should be performed in Asian patients with SqCC diagnosed from small lung biopsies, especially in never-smokers and patients with diagnosis of NSCC favor SqCC, which have a high probability of being ADSC.

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Section: Methodsmentioning

confidence: 99%

The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies

Kao

Yeh

et al. 2019

Diagn Pathol

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“…Data on patient demographics, clinicopathologic characteristics, and outcomes were collected retrospectively from medical records. EGFR mutation status was previously determined for lung adenocarcinomas in cohort B [ 25 ]. Overall survival (OS) was defined as the interval between the date of surgical resection and that of either death or last follow-up.…”

Section: Methodsmentioning

confidence: 99%

HighO-linkedN-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma

Lin

Lin²,

Yeh

et al. 2018

Oncotarget

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Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge. Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies. O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis. O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA) catalyze O-GlcNAc addition and removal, respectively. We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma. We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035). High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038). Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411–6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183–3.391, P=0.010) in stage I patients. Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.

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“…The increase in the number of therapeutic targets for detection on smaller and smaller samples has led to the development of algorithms for use with IHC in combination with MB techniques [ 8 , 45 , 107 , 108 ]. Irrespective of the algorithm they must integrate different parameters that can be modified from case to case.…”

Section: Which Algorithms? For Which Patients? For Which Samples?mentioning

confidence: 99%

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

Hofman

Lassalle

Bence

et al. 2018

Cancers

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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.

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Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence in situ hybridization methods

Cited by 11 publications

References 39 publications

The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies

The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies

HighO-linkedN-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma

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

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