Correlation of anaplastic lymphoma kinase overexpression and the EML4-ALK fusion gene in non-small cell lung cancer by immunohistochemical study

Chen, Tai‐Di; Chang, I–Shou; Liu, Huiping; Wu, Yi‐Cheng; Wang, Chi-Liang; Chen, Ya‐Ting; Chen, Yirong; Huang, Shiu-Feng

doi:10.4103/2319-4170.106140

Cited by 5 publications

(1 citation statement)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides chromosome rearrangements, gene overexpression has been described as the relevant abnormal alterations in the ALK gene in neuroblastoma, lung, and oesophageal cancer [22][23][24]. Chen et al (2012) also showed ALK overexpression in non-small cell lung cancer detected by immunohistochemical techniques [25]. Another recent evidence demonstrated that the ovarian high-grade serous carcinoma (HGSC) had significantly higher cytoplasmic ALK expression without chromosomal rearrangement or gene alterations compared to non-HGSC ovarian carcinomas [26].…”

Section: Discussionmentioning

confidence: 99%

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer

et al. 2022

View full text Add to dashboard Cite

Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy. Our results demonstrate that among 147 kinase inhibitors (KI), only three molecules were significantly cytotoxic for the AGP-01 cell line. Hence, these three molecules were further characterized in their cellular mode of action. There was significant cell cycle impairment due to the expression modulation of genes such as TP53, CDKN1A, CDC25A, MYC, and CDK2 with subsequent induction of apoptosis. In fact, the Gene Ontology analysis revealed a significant enrichment of pathways related to cell cycle regulation (GO:1902749 and GO:1903047). Moreover, the three selected KIs significantly reduced cell migration and Vimentin mRNA expression after treatment. Surprisingly, the three KIs share the same target, ALK and INSR, but only the ALK gene was found to have a high expression level in the gastric cancer cell line. Additionally, lower survival rates were observed for patients with high ALK expression in TCGA-STAD analysis. In summary, we hypothesize that ALK gene overexpression can be a promising biomarker for prognosis and therapeutic management of gastric adenocarcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma

Matsumura

Umemura

Ishii

et al. 2015

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Background As the comprehensive genomic analysis of small cell lung cancer (SCLC) progresses, novel treatments for this disease need to be explored. With attention to the direct connection between the receptor tyrosine kinases (RTKs) of tumor cells and the pharmacological effects of specific inhibitors, we systematically assessed the RTK expressions of high-grade neuroendocrine carcinomas of the lung [HGNECs, including SCLC and large cell neuroendocrine carcinoma (LCNEC)].Patients and methodsFifty-one LCNEC and 61 SCLC patients who underwent surgical resection were enrolled in this research. As a control group, 202 patients with adenocarcinomas (ADCs) and 122 patients with squamous cell carcinomas (SQCCs) were also analyzed. All the tumors were stained with antibodies for 10 RTKs: c-Kit, EGFR, IGF1R, KDR, ERBB2, FGFR1, c-Met, ALK, RET, and ROS1.ResultsThe LCNEC and SCLC patients exhibited similar clinicopathological characteristics. The IHC scores for each RTK were almost equivalent between the LCNEC and SCLC groups, but they were significantly different from those of the ADC or SQCC groups. In particular, c-Kit was the only RTK that was remarkably expressed in both LCNECs and SCLCs. On the other hand, about 20 % of the HGNEC tumors exhibited strongly positive RTK expression, and this rate was similar to those for the ADC and SQCC tumors. Intriguingly, strongly positive RTKs were almost mutually exclusive in individual tumors.ConclusionsCompared with ADC or SQCC, LCNEC and SCLC had similar expression profiles for the major RTKs. The exclusive c-Kit positivity observed among HGNECs suggests that c-Kit might be a distinctive RTK in HGNEC.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-015-1989-z) contains supplementary material, which is available to authorized users.

show abstract

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non‐small cell lung cancer

Chen

Lei

et al. 2019

Thoracic Cancer

View full text Add to dashboard Cite

Background Both genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non‐tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied. Methods We selected 410 non‐small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription‐PCR was performed to detect ALK , ROS1 , RET , and NTRK1 rearrangement. Results Among the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty‐seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4‐ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure. Conclusion FLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.

show abstract

Correlation of anaplastic lymphoma kinase overexpression and the EML4-ALK fusion gene in non-small cell lung cancer by immunohistochemical study

Cited by 5 publications

References 29 publications

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer

Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non‐small cell lung cancer

Contact Info

Product

Resources

About