Oncogenic driver mutations in patients with non-small-cell lung cancer at various clinical stages

Zhou, Jeff X.; Yang, Huanming; Deng, Qiuhua; Gu, Xia; He, Ping; Lin, Yu; Zhao, Meiling; Jiang, Juhong; Chen, H.; Yin, Weiqiang; Mo, Lijuan; He, Jianxing

doi:10.1093/annonc/mds626

Cited by 70 publications

(68 citation statements)

References 28 publications

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“…According to this study, the mutation rate in patients with well-differentiated tumors was 83.33%, in patients with moderately differentiated tumors 46.43% and in patients with poorly differentiated tumors 41.18%, which was inconsistent with previous findings (3). This inconsistency may be attributed to the lack of well-differentiated cases in this study; therefore a larger sample size is required to confirm this result (11,22). In addition, no statistical association was observed between lymph node metastasis, TNM stage and EGFR mutation (P>0.05), which was in agreement with the findings of Li et al (1).…”

Section: Discussionsupporting

confidence: 82%

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Epidermal growth factor receptor gene mutation status and its association with clinical characteristics and tumor markers in non-small-cell lung cancer patients in Northwest China

Abdurahman

Anwar

Turghun

et al. 2015

Molecular and Clinical Oncology

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Abstract. This study was conducted to investigate the mutation status of epidermal growth factor receptor (EGFR) and its association with clinical characteristics and tumor markers in non-small-cell lung cancer (NSCLC) patients from the Xinjiang Uygur Autonomous Region in China. We enrolled 51 cases of NSCLC patients who received radical surgical treatment in the First Affiliated Hospital of Xinjiang Medical University. Quantitative polymerase chain reaction was applied to detect exons 18, 19, 20 and 21 of the EGFR gene in tumor tissues. Multiple tumor markers, including carcinoembryonic antigen (CEA), were assessed preoperatively. The EGFR-positive rate was 49.02% (25/51), with a mutation rate of 8% (2/25) in exon 18, 52% (13/51) in exon 19, 40% (10/51) in exon 21 and no mutations in exon 20. The positive mutation rate in men and women was 37.5% (12/32) and 68.42%, respectively (13/19), with a statistically significantly higher rate in women (P<0.05). There were also statistically significant differences among adenocarcinoma, adenosquamous carcinoma and squamous cell carcinoma cases (P<0.05), while no statistically significant differences were observed in adenocarcinoma cases regarding degree of differentiation, lymph node metastasis and TNM stage (P>0.05). There was a statistically significant association between the EGFR gene mutation status and the preoperative serum CEA level (P<0.05). The mutation rate of the EGFR gene was 68.42% in female lung adenocarcinoma patients, which supports the application of targeted therapy in such cases. However, whether it is possible to obtain information regarding targeted therapy through measuring the level of serum CEA for NSCLC patients with unknown EGFR mutation status requires further investigation through related studies including a higher number of cases. IntroductionLung cancer is one of the most common malignant tumors in humans, with an equally high incidence in men and in women. Approximately 80% of lung cancer cases are non-small-cell lung cancer (NSCLC) (1). The majority of the patients present with advanced-stage lung cancer at diagnosis, when radical excision is no longer feasible (2) and the remaining treatment options include radiotherapy, chemotherapy and immune therapy. The rate of response to radiotherapy and chemotherapy is only 15-35%, which may not effectively improve the survival rate and life quality of the patients. Therefore, the total 5-year survival rate of lung cancer patients is only ~15% (2-4).Over the last few years, genetic testing and targeted therapy based on epidermal growth factor receptor (EGFR) gene mutation status has attracted significant attention. Multiple clinical studies indicated that tyrosine kinase inhibitors (TKIs) have effectively extended the survival time and improved the life quality of NSCLC patients (5), with a total effectiveness rate of >70%. However, the effectiveness rate of TKI treatment for wild-type EGFR cancers is only 10-15% (6). Therefore, it is crucial to determine the mutation status of the EGFR gene in NSC...

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Section: Discussionsupporting

confidence: 82%

“…Although there have been significant advances in the comprehensive treatment of lung cancer, the 5-year survival rate and life quality of the patients remain very low (11). The traditional radiotherapy and chemotherapy are associated with significant toxicity and side effects due to the lack of specificity (1).…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor gene mutation status and its association with clinical characteristics and tumor markers in non-small-cell lung cancer patients in Northwest China

Abdurahman

Anwar

Turghun

et al. 2015

Molecular and Clinical Oncology

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“…However, ALK rearrangements have been found in older patients and smokers (34), squamous cell and adenosquamous carcinoma cases (35, 36), and rarely, patients with mutations in EGFR , Kirsten rat sarcoma viral oncogene homolog ( KRAS ), and B-Raf proto-oncogene, serine/threonine kinase ( BRAF ) (20 –22, 37, 38). Although the triage of samples based on clinicopathological features does increase the success rate of detection of ALK rearrangements (33), it is not an optimal strategy, since a portion of patients who could benefit from ALK inhibitors would unavoidably be excluded (4, 39, 40).…”

Section: Discussionmentioning

confidence: 99%

Quantification of Anaplastic Lymphoma Kinase Protein Expression in Non–Small Cell Lung Cancer Tissues from Patients Treated with Crizotinib

et al. 2016

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BACKGROUND Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non–small cell lung cancer (NSCLC). The current diagnostic test for ALK rearrangement is breakapart fluorescence in situ hybridization (FISH), but FISH has low throughput and is not always reflective of protein concentrations. The emergence of multiple clinically relevant biomarkers in NSCLC necessitates efficient testing of scarce tissue samples. We developed an anaplastic lymphoma kinase (ALK) protein assay that uses multiplexed selected reaction monitoring (SRM) to quantify absolute amounts of ALK in formalin-fixed paraffin-embedded (FFPE) tumor tissue. METHODS After validation in formalin-fixed cell lines, the SRM assay was used to quantify concentrations of ALK in 18 FFPE NSCLC samples that had been tested for ALK by FISH and immunohistochemistry. Results were correlated with patient response to crizotinib. RESULTS We detected ALK in 11 of 14 NSCLC samples with known ALK rearrangements by FISH. Absolute ALK concentrations correlated with clinical response in 5 of 8 patients treated with crizotinib. The SRM assay did not detect ALK in 3 FISH-positive patients who had not responded to crizotinib. In 1 of these cases, DNA sequencing revealed a point mutation that predicts a nonfunctional ALK fusion protein. The SRM assay did not detect ALK in any tumor tissue with a negative ALK status by FISH or immunohistochemistry. CONCLUSIONS ALK concentrations measured by SRM correlate with crizotinib response in NSCLC patients. The ALK SRM proteomic assay, which may be multiplexed with other clinically relevant proteins, allows for rapid identification of patients potentially eligible for targeted therapies.

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“…One study of resected lung adenocarcinomas, however, found that ALK or ROS1 fusion-positive tumors have a significantly poorer disease free survival on multivariate analysis after adjusting for age, gender, T stage, N stage and adjuvant chemotherapy use (p ¼ 0.022; hazard ratio, 2.11) 2 . Another study of patients with non-small-cell lung cancer at various clinical stages found that stage IIIA EML4-ALK positive patients has a worse disease free survival on multivariate analyses, further establishing the oncogene addicted nature of these tumors 3 .…”

mentioning

confidence: 94%

Similitude and evolution of treatment algorithms

Kelleher

2015

Current Medical Research and Opinion

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Oncogenic driver mutations in patients with non-small-cell lung cancer at various clinical stages

Cited by 70 publications

References 28 publications

Epidermal growth factor receptor gene mutation status and its association with clinical characteristics and tumor markers in non-small-cell lung cancer patients in Northwest China

Epidermal growth factor receptor gene mutation status and its association with clinical characteristics and tumor markers in non-small-cell lung cancer patients in Northwest China

Quantification of Anaplastic Lymphoma Kinase Protein Expression in Non–Small Cell Lung Cancer Tissues from Patients Treated with Crizotinib

Similitude and evolution of treatment algorithms

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