<i>ALK</i>Rearrangement in a Large Series of Consecutive Non–Small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescence In Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment

Alì, Greta; Proietti, Agnese; Pelliccioni, Serena; Niccoli, Cristina; Lupi, Cristiana; Sensi, Elisa; Giannini, Raffaello; Borrelli, Nicla; Menghi, Maura; Chella, Antonio; Ricci, Alessandro; Cappuzzo, Federico; Melfi, Franca; Lucchi, Marco; Mussi, Alfredo; Fontanini, Gabriella

doi:10.5858/arpa.2013-0388-oa

Cited by 83 publications

(50 citation statements)

References 40 publications

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“…Formalin‐fixed paraffin‐embedded samples were sectioned at a thickness of 4 μm and subjected to immunohistochemical staining with a rabbit monoclonal primary anti‐ALK antibody (clone D5F3) using the OptiView DAB IHC Detection Kit and the OptiView Amplification Kit (Ventana Medical Systems Inc., Tucson, AZ, USA). The entire staining procedure was performed using the fully automated assay using BenchMark XT slide stainer system (Ventana Medical Systems Inc.) . Positive immunostaining for ALK was clearly visible as strong, granular, cytoplasmic staining in tumour cells.…”

Section: Methodsmentioning

confidence: 99%

Correlation between pre‐treatment serum carcinoembryonic antigen levels and genotypes in a large population of Chinese people with advanced lung adenocarcinoma

Liu

Zhao

Han

et al. 2019

Internal Medicine Journal

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Background A positive correlation between serum carcinoembryonic antigen (CEA) levels and epidermal growth factor receptor (EGFR) mutations has been reported in lung adenocarcinoma patients. Aim To investigate retrospectively whether serum CEA levels are also associated with genotypes in a large population of advanced lung adenocarcinoma. Methods A large cohort of 701 patients with advanced lung adenocarcinoma was studied retrospectively. Results EGFR mutations were found in 47.5% (333/701) of advanced lung adenocarcinoma patients, being identified at high frequencies in never‐smokers, females, and in patients with abnormal pre‐treatment serum CEA levels (53.1% vs 37.5%, P < 0.001). In contrast, anaplastic lymphoma kinase gene rearrangements were found in 7.8% (55/701) of patients, being identified at high frequencies in younger patients, and in patients with normal CEA levels (11.5% vs 5.8%, P = 0.012). Serum CEA levels were divided into four groups: <5, 5–19, 20–99 and ≥100 ng/mL. The rate of EGFR mutations significantly increased as the serum CEA levels increased (37.5%, 49.5%, 53.9% and 57.7%, respectively, P < 0.001). Anaplastic lymphoma kinase gene rearrangements showed the opposite result (11.5%, 7.1%, 5.7% and 4.1%, respectively, P = 0.044). A multivariate analysis revealed that higher pre‐treatment serum CEA levels were independently associated with EGFR mutations (95% CI: 1.291–2.487, P < 0.001), but normal serum CEA levels were independently associated with anaplastic lymphoma kinase gene rearrangements (95% CI: 0.275–0.842, P = 0.010). Conclusion Our study demonstrated that a significant association exists between the serum CEA levels and genotypes in patients with advanced lung adenocarcinoma.

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Section: Methodsmentioning

confidence: 99%

Correlation between pre‐treatment serum carcinoembryonic antigen levels and genotypes in a large population of Chinese people with advanced lung adenocarcinoma

Liu

Zhao

Han

et al. 2019

Internal Medicine Journal

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“…We used Deek's funnel plots of lnDOR against 1/ESS 1/2 , or, equivalently, against (1/ n 1 + 1/ n 2) 1/2 , which is proportional to 1/ESS 1/2 , to assess the accuracy of diagnostic tests [40]. The p value obtained from the funnel plot was 0.001, indicating the presence of publication bias in this meta-analysis (Figure 10).…”

Section: Resultsmentioning

confidence: 99%

“…PCR, another method for detecting ALK fusion, is associated with high false positive rates, limiting its clinical utility. Some researchers have reported that IHC, a cost-effective and simple assay, can be used to screen for ALK rearrangements [40, 54], and three different antibodies are used for this purpose in clinical practice. D5F3, one of these antibodies, is widely used in clinics; we therefore conducted this systematic review and meta-analysis to assess the diagnostic accuracy of D5F3 IHC assays in detecting ALK rearrangement in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis

Yao

Huang

et al. 2016

Oncotarget

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We conducted a pooled analysis comparing the efficacy of an immunohistochemistry (IHC) assay using the D5F3 antibody with that of fluorescence in situ hybridization (FISH) for detecting ALK gene rearrangement in NSCLC patients. A total of 32 studies involving 5805 samples were included in this review. Pooled sensitivity for D5F3 IHC was 0.97 (95%CI: 0.93-0.98), specificity was 0.99 (95%CI: 0.98-1.00), PLR was 119.20 (95%CI: 57.79-245.89), NLR was 0.03 (95%CI: 0.02-0.07), DOR was 3526.66 (95%CI: 1344.71-9249.03), and AUROC was 1.00 (95%CI: 0.99-1.00). Meta-regression revealed that specimen type was a source of heterogeneity for specificity, and specimen type and FISH signal distance were sources of heterogeneity in the joint model. Subgroup analysis revealed that sensitivity and specificity were higher when the FISH signal distance standard was ≥ 2 than when it was ≥ 1. Sensitivity was higher for tumor specimens than for cell specimens; specificity was higher for cell specimens than for tumor specimens. In conclusion, the D5F3 IHC assay was nearly as effective as FISH for detection of ALK gene rearrangement in NSCLC patients.

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“…Squamous histology has a lower rate of actionable genetic changes than adenocarcinoma of the lung, but epidermal growth factor mutations and anaplastic lymphoma receptor tyrosine kinase rearrangements, for example, have been described in squamous cases, albeit rarely. 3,4 In reality, histology is a subjective determination by a pathologist. Previous reports have suggested very low k-values for agreement between pathologists on whether an NSCLC exhibits squamous histology.…”

Section: Ross Camidgementioning

confidence: 99%

Drinking Not Drowning: How to Deal With the Deluge of Potential Predictive Biomarker Approaches in Non–Small-Cell Lung Cancer

Camidge

2017

JOP

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ALKRearrangement in a Large Series of Consecutive Non–Small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescence In Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment

Abstract: Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

Cited by 83 publications

References 40 publications

Correlation between pre‐treatment serum carcinoembryonic antigen levels and genotypes in a large population of Chinese people with advanced lung adenocarcinoma

Correlation between pre‐treatment serum carcinoembryonic antigen levels and genotypes in a large population of Chinese people with advanced lung adenocarcinoma

Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis

Drinking Not Drowning: How to Deal With the Deluge of Potential Predictive Biomarker Approaches in Non–Small-Cell Lung Cancer

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