Suitability of Surgical Tumor Tissues, Biopsy, or Cytology Samples for Epidermal Growth Factor Receptor Mutation Testing in Non–Small Cell Lung Carcinoma Based on Chinese Population

Han, Xiaohong; Zhang, Zhishang; Wu, Di; Shen, Yao; Wang, Shuai; Wang, Lin; Liu, Yutao; Yang, Sheng; Hu, Xingsheng; Feng, Yun; Sun, Yan; Shi, Yuankai

doi:10.1016/j.tranon.2014.10.008

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…Primary and metastatic site biopsies from B+/T-and B+/T+ groups predicted a better response to EGFR-TKIs than biopsies from the B-/T+ group; however, this trend did not apply to resected tissues. Resected samples from early-stage surgeries may have different biological and genetic characteristics compared with advanced-stage metastatic tumor cells (24,25). Another important factor is that adjuvant chemotherapy may influence EGFR mutation status (18).…”

Section: Pfs Time Months ----------------------------------------mentioning

confidence: 99%

Analysis of EGFR mutation status in tissue and plasma for predicting response to EGFR-TKIs in advanced non-small-cell lung cancer

Wang¹,

Duan²,

Chen³

et al. 2017

Oncology Letters

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Abstract. The detection of mutations in the epidermal growth factor receptor (EGFR) gene in tumor tissues has been established as the gold standard for predicting the efficacy of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer (NSCLC). The current study aimed to investigate whether the presence of co-existing EGFR mutations in tumor tissue and in cell-free tumor DNA (ctDNA) in the plasma predicts a more favorable outcome of EGFR-TKI treatment in advanced NSCLC. A total of 287 NSCLC patients who had undergone EGFR-TKI treatment were enrolled and stratified into four subgroups: Wild-type EGFR in plasma and tissue specimens (B-/T-); mutated EGFR in plasma and tissue specimens (B+/T+); mutated EGFR in only in plasma samples (B+/T-); or mutated EGFR in only tissue specimens (B-/T+). EGFR mutations were tested using denaturing high-performance liquid chromatography and confirmed by amplification-refractory mutation system analysis. Of the 287 patients, 101 had mutations in both tissue and plasma samples and 103 had mutation in either tissue (n=65) or plasma (n=38). The median progression-free survival (mPFS) times were 9.2 and 2.0 months in the B+/T+ and B-/T-groups, respectively. The mPFS times were 7.9 months in the B-/T+ group and 11.9 months in the B+/T-group (P=0.001). Among the 187 patients with available pre-EGFR-TKI plasma samples, 70 received first-line EGFR-TKI treatment, and the mPFS in the B+/T+ group was longer than in the B-/T+ or B+/Tgroups (18.8 vs. 9.4 vs. 6.9 months; P= 0.003). In second-line setting of EGFR-TKI therapy, the groups of patients with EGFR mutation in ctDNA, regardless of the mutation status in the tissues, exhibited longer mPFS times compared with the B-/T+ group (10.0 vs. 5.8 months; P=0.044). The results suggest that co-existence of EGFR mutations in tissue and ctDNA predict longer PFS times for NSCLC patients who receive first-line EGFR-TKI therapy. In addition, real-time detection in ctDNA is an excellent predictor for the efficacy of second-or higher line EGFR-TKI therapy.

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Section: Pfs Time Months ----------------------------------------mentioning

confidence: 99%

Analysis of EGFR mutation status in tissue and plasma for predicting response to EGFR-TKIs in advanced non-small-cell lung cancer

Wang¹,

Duan²,

Chen³

et al. 2017

Oncology Letters

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“…Moreover, genetic alterations within the tumours change the molecular marker profile during the course of the disease. Currently, most advanced NSCLC patients are diagnosed using biopsies or cytology specimens, due to a lack of availability of resected tumour tissue [5]. However, in many patients, adequate diagnostic sampling is problematic, both de novo and post-EGFR therapy.…”

Section: Introductionmentioning

confidence: 99%

The expression of circulating miR-504 in plasma is associated with EGFR mutation status in non-small-cell lung carcinoma patients

Szpechcinski¹,

Florczuk²,

Duk³

et al. 2019

Cell. Mol. Life Sci.

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MicroRNAs (miRNAs), key regulators of gene expression at the post-transcriptional level, are grossly misregulated in some human cancers, including non-small-cell lung carcinoma (NSCLC). The aberrant expression of specific miRNAs results in the abnormal regulation of key components of signalling pathways in tumour cells. MiRNA levels and the activity of the gene targets, including oncogenes and tumour suppressors, produce feedback that changes miRNA expression levels and indicates the cell’s genetic activity. In this study, we measured the expression of five circulating miRNAs (miR-195, miR-504, miR-122, miR-10b and miR-21) and evaluated their association with EPIDERMAL GROWTH FACTOR RECEPTOR ( EGFR ) mutation status in 66 NSCLC patients. Moreover, we examined the discriminative power of circulating miRNAs for EGFR mutant‐positive and -negative NSCLC patients using two different data normalisation approaches. We extracted total RNA from the plasma of 66 non-squamous NSCLC patients (31 of whom had tumours with EGFR mutations) and measured circulating miRNA levels using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The miRNA expression levels were normalised using two endogenous controls: miR-191 and miR-16. We found significant associations between the expression of circulating miR-504 and EGFR -activating mutations in NSCLC patients regardless of the normalisation approach used ( p = 0.0072 and 0.0236 for miR-16 and miR-191 normalisation, respectively). The greatest discriminative power of circulating miR-504 was observed in patients with EGFR exon 19 deletions versus wild-type EGFR normalised to miR-191 (area under the curve (AUC) = 0.81, p < 0.0001). Interestingly, circulating miR-504 levels were significantly reduced in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS )-mutated subgroup compared to EGFR -mutated patients ( p < 0.0030) and those with EGFR/KRAS wild-type tumours ( p < 0.0359). Our study demonstrated the feasibility and potential diagnostic value of plasma miR-504 expression analysis to distinguish between EGFR -mutated and wild-type NSCLC patients. However, quality control and normalisation strategies are very important and have a major impact on the outcomes of circulating miRNA analyses.

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“…Researchers have found that the mutation frequency of EGFR mutated patients is closely relevant to tumor node metastasis (TNM) staging, especially to lymphatic metastasis, and the drug-resistant mutation of T790M occurs most commonly in advanced lung cancer. 21,22 A meta-analysis containing 27 retrospective studies and 6950 lung cancer patients revealed that the frequency of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene fusion in advanced lung cancer is significantly higher than in early stage. 23 Data from a study of wholegenome sequencing in Asian patients demonstrated a large difference in genetic background between early and advanced lung cancer.…”

Section: Introductionmentioning

confidence: 99%

High‐fidelity of non‐small cell lung cancer xenograft models derived from bronchoscopy‐guided biopsies

Zhao

Bai

et al. 2015

Thoracic Cancer

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BackgroundAt present, there are two main types of lung cancer xenograft models: those derived from stable cell lines, and patient‐derived xenograft models established by surgically resected tissues. However, these animal models may not reflect the biological and genetic characteristics of advanced non‐small cell lung cancer (NSCLC). We utilized bronchoscopy‐guided biopsy tissues of NSCLC patients to establish xenograft models and analyzed their histopathologic and genotypic fidelity with parental tumors.MethodsTumor tissues of NSCLC patients taken via bronchoscope were subcutaneously implanted into mice with non‐obese diabetic‐severe combined immunodeficiency disease for model establishment and serial passage. The histopathology and genotype of the samples from bronchoscopy‐guided biopsy‐derived xenograft (BDX) models and their parental tumors were detected.ResultsThirty BDXs out of 114 NSCLC patients (26.32%) were successfully established. Smoking status significantly affected the success rate of NSCLC BDX establishment (P = 0.010). The BDX establishment success rate in squamous cell cancer was higher than in adenocarcinoma, with no significant difference (32.00% vs. 16.21%, P = 0.112). However, the growth rate of passage 1 BDX was slower than that of passages 2 and 3. Almost all NSCLC BDXs maintained similarity to their parental tumor tissues in regard to histologic characteristics, pathological markers, and driver‐gene mutations. Only one BDX model lost the epidermal growth factor receptor mutation contained in tumor parental tissue, as a result of heterogeneity.Conclusions NSCLC BDXs maintained high fidelity of histopathology and genotype with their original tumors. NSCLC BDXs that possess the actual status of advanced lung carcinoma should be used in preclinical research.

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Suitability of Surgical Tumor Tissues, Biopsy, or Cytology Samples for Epidermal Growth Factor Receptor Mutation Testing in Non–Small Cell Lung Carcinoma Based on Chinese Population

Cited by 7 publications

References 37 publications

Analysis of EGFR mutation status in tissue and plasma for predicting response to EGFR-TKIs in advanced non-small-cell lung cancer

Analysis of EGFR mutation status in tissue and plasma for predicting response to EGFR-TKIs in advanced non-small-cell lung cancer

The expression of circulating miR-504 in plasma is associated with EGFR mutation status in non-small-cell lung carcinoma patients

High‐fidelity of non‐small cell lung cancer xenograft models derived from bronchoscopy‐guided biopsies

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