Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma

Go, Heounjeong; Jung, Yoo Jin; Kang, Hyun-Gyu; Park, In Kyu; Kang, Chang Hyun; Lee, Jung Wan; Ju, Young Seok; Seo, Jeong Sun; Chung, Doo Hyun; Kim, Young Tae

doi:10.1016/j.lungcan.2013.07.009

Cited by 46 publications

(40 citation statements)

References 23 publications

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“…11 Similarly, another study showed no significant differences between RET IHC staining patterns among RET-positive and RET-negative specimens previously identified by RT-PCR, and the FN and FP rates by IHC were 46% and 62%, respectively. 10 Furthermore, three retrospective analyses 9,45,48 confirmed the poor performance of IHC in detecting RET rearrangement, with 33% to 43% FN and 14% FP results, whereas 100% agreement was demonstrated between WGS, FISH, and RT-PCR. 45 Although these data clearly indicate that IHC is not a reliable technique to detect RET rearrangement because of the low sensitivity (55%-65%) and highly variable specificity (40%-85%), given the discrepancy between the cutoffs to define IHC positivity (10% 63 -30% 45 of cells with RET staining) and the antibodies used, interpretation cannot be generalized.…”

Section: Molecular Diagnosticsmentioning

confidence: 88%

“…Thus, the prevalence of the RET fusion gene is 0.9% to 1.8% in lung adenocarcinoma and 6% to 14% in adenocarcinomas WT for other molecular drivers (Table 1). 11,[44][45][46][47][48] In NSCLC, at least 12 fusion RET partner genes have been identified to date (KIF5B-RET, [11][12][13]44 gene CCDC6-RET, 12 53 and tripartite motif containing 24 gene [TRIM24]-RET 53 ); some of them are represented in Figure 2. KIF5B, with its 10 Figure 1.…”

Section: Biology and Fusion Partnersmentioning

confidence: 99%

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Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer

Ferrara

Auger

Auclin

et al. 2018

Journal of Thoracic Oncology

176

151

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Since the discovery in 2012 of rearranged during transfection proto-oncogene gene (RET) rearrangements in NSCLC, at least 12 different fusion variants have been identified, with kinesin family member 5B gene (KIF5B)-RET being the most frequent and the best characterized. Unlike ALK receptor tyrosine kinase gene (ALK) and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry (IHC), although fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histologic subtype, never-smoking status, younger age, more advanced disease stage, potentially higher chemosensitivity (in particular, to pemetrexed-based regimens), and coexistence of other genomic alterations. To date, several preclinical models, clinical trials, and retrospective studies have investigated multitarget inhibitors with anti-rearranged during transfection proto-oncogene (RET) activity in patients with RET-rearranged lung cancer. In the clinical setting, the benefit in terms of response (16%-47%) and progression-free survival (2-7 months) is clearly not comparable to that seen with other targeted agents in oncogene-addicted NSCLC. Furthermore, multikinase agents showed high rates of severe toxicities, leading to frequent dose reduction and drug discontinuation. To date, no definitive conclusions about a potentially different impact of anti-RET therapies according to RET fusion variants have been drawn on account of discordant data coming mostly from small subgroup analyses. Importantly, the absence of a striking clinical benefit in RET oncogene-addicted NSCLC underscores the clear need for development of more selective and potent RET inhibitors and for better characterization of concomitant genomic alterations and mechanisms of resistance to RET inhibition in patients with lung cancer.

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Section: Molecular Diagnosticsmentioning

confidence: 88%

Section: Biology and Fusion Partnersmentioning

confidence: 99%

Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer

Ferrara

Auger

Auclin

et al. 2018

Journal of Thoracic Oncology

176

151

View full text Add to dashboard Cite

show abstract

“…Akciğer adenokarsinomlarının yaklaşık %1-2'sinde görülür ve yine sıklıkla sigara kullanmamış hastalarda saptanır (28,29,30). RET gen değişiklikleri FİSH yöntemiyle saptanabilir, ayrıca sekanslama veya PCR yöntemlerinin daha faydalı olacağı düşünülmektedir (31). İmmünhistokimyasal yöntemlerin henüz RET rearranjmanı tespitinde net bir yeri yoktur.…”

Section: Ret Rearranjmanıunclassified

Molecular Pathology of Lung Cancer

Bozkurtlar¹,

Kaya²

2018

Nts

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“…Currently RET antibodies are insufficiently sensitive to detect RET rearrangements in lung cancer. 64,65 Immunohistochemistry using BRAF V600E mutationspecific antibodies has established good sensitivity and specificity in melanoma, thyroid, and colon cancers. However, lung ADC-harboring BRAF mutations are rare, only about half of them being V600E.…”

mentioning

confidence: 99%

Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update

Zhang

Deng

Cagle

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Immunohistochemistry has become an indispensable ancillary tool for the accurate classification of pleuropulmonary and mediastinal neoplasms necessary for therapeutic decisions and predicting prognostic outcome in the era of personalized medicine. Diagnostic accuracy has significantly improved because of the continuous discoveries of tumor-associated biomarkers and the development of effective immunohistochemical panels.Objective.-To increase the accuracy of diagnosis and classify pleuropulmonary neoplasms through immunohistochemistry.Data Sources.-Literature review, authors' research data, and personal practice experience.Conclusions.-This review article has shown that appropriately selecting immunohistochemical panels enables pathologists to effectively diagnose most primary pleuropulmonary neoplasms and differentiate primary lung tumors from a variety of metastatic tumors to the lung. The discovery of new mutation-specific antibodies identifying a subset of specific gene-arranged lung tumors provides a promising alternative and cost-effective approach to molecular testing. Knowing the utilities and pitfalls of each tumor-associated biomarker is essential to avoiding potential diagnostic errors.

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Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma

Cited by 46 publications

References 23 publications

Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer

Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer

Molecular Pathology of Lung Cancer

Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update

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