Detection of <i>ALK</i> rearrangements in malignant pleural effusion cell blocks from patients with advanced non‐small cell lung cancer: A comparison of Ventana immunohistochemistry and fluorescence in situ hybridization

Wang, Weiya; Tang, Yuan; Li, Jinnan; Jiang, Lili; Jiang, Yong; Su, Xiaorui

doi:10.1002/cncy.21510

Cited by 56 publications

(51 citation statements)

References 24 publications

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“…Different clones and innate tumor heterogeneity of samples may attribute to the discrepancy (29)(30)(31). Previous studies reported that IHC assay was a valuable tool for the screening of patients with ALK rearrangement in clinical practice (7,32,33), IHC with new antibody and modified protocols will extend its serviceable range for detecting ALK rearrangement (34). Although FISH was approved by Food and Drug Administration as a companion diagnostics, FISH required specialized equipment and highly trained and skilled readers for interpretation because of variability between inter-observers.…”

Section: Discussionmentioning

confidence: 99%

High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

Hou

Ren

Su³

et al. 2016

J. Thorac. Dis.

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Background: Lung cancer has heterogeneous features. It remains unclear whether ALK rearrangement was distributed heterogeneously in tumor from different anatomic sites. To address this issue, we investigate the concordance of ALK rearrangement between primary tumors and paired metastatic lymph nodes in pulmonary adenocarcinoma patients. Results: A total of 101 patients were enrolled into this study with a median age of 60 years old (range, 35-78 years). ALK rearrangement was found in 20 primary lesions, while in 18 paired metastatic lymph nodes. ALK rearrangement was more frequently happened in younger (P<0.001), Nonsmokers (P=0.012), high-stage disease (P=0.021) and predominantly solid growth pattern (P=0.024). The concordance rate between primary tumor and paired metastatic lymph nodes was 98%. Two patients with ALK rearrangement on primary tumor didn't show ALK gene fusion on paired metastatic lymph nodes. Sixty-eight cases had more than two stations of metastatic lymph nodes. ALK rearrangement in the different station of metastatic lymph nodes of the same patient was consistent.Conclusions: High concordant rate of ALK rearrangement between primary tumors and paired metastatic lymph nodes were found in this study. The authors concluded that specimens from metastatic lesions and primary tumors are equally suitable for detection ALK rearrangement.

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Section: Discussionmentioning

confidence: 99%

High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

Hou

Ren

Su³

et al. 2016

J. Thorac. Dis.

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“…FISH using fresh pleural fluid samples should be considered as an additional informative assay for pleural effusions suspicious of being malignant [40, 41]. Furthermore, cell block preparations are commonly used for diagnostic pathology and gene analysis by FISH and IHC [42, 43]. A few reports reported that compared with tumor tissue, pleural effusion cell block had 81.8% sensitivity and 80% specificity for detection of EGFR mutation [44] and 62.5% to 100% sensitivity and 100% specificity for ALK detection [43].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center Retrospective Analysis

et al. 2016

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BackgroundSome trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion.MethodsData from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site.ResultsThirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy.ConclusionPleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic approach for malignant pleural diseases presenting with effusion.

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“…Although there have been some previous case reports of the efficacy of ALK -tyrosine kinase inhibitor (TKI) therapy in patients in whom ALK protein expression was detected in MPE samples (31,32), we obtained efficacy data with crizotinib in a total of 11 lung adenocarcinoma patients who were Ventana IHC ALK (D5F3)-positive. Two patients had CR (2/11, 18.2%), 5 had PR (5/11, 45.5%), and 3 had SD (3/11, 27.3%).…”

Section: Discussionmentioning

confidence: 99%

ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma

Wang

Han

et al. 2016

Chinese Journal of Cancer Research

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ObjectiveThe relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain. MethodsVentana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded. ResultsOf the 313 MPE samples, 27 (8.6%) were confirmed as ALK expression-positive, and the Ventana IHC ALK (D5F3)-positive rate was 17.3% (27/156) in wild-type epidermal growth factor receptor (EGFR) MPE samples. Twenty-three of the 27 IHC ALK (D5F3)-positive samples were positive by FISH. Of the 11 Ventana IHC ALK (D5F3)-positive patients who received crizotinib therapy, 2 patients had complete response (CR), 5 had partial response (PR) and 3 had stable disease (SD). ConclusionsThe ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.

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Detection of ALK rearrangements in malignant pleural effusion cell blocks from patients with advanced non‐small cell lung cancer: A comparison of Ventana immunohistochemistry and fluorescence in situ hybridization

Abstract: KEY WORDS: non-small cell lung cancer; anaplastic lymphoma kinase (ALK); Ventana immunohistochemistry (IHC) assay; fluorescence; fluorescence in situ hybridization (FISH); malignant pleural effusion; cell block.

Cited by 56 publications

References 24 publications

High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center Retrospective Analysis

ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma

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