Immunohistochemistry is a Reliable Screening Tool for Identification of ALK Rearrangement in Non–Small-Cell Lung Carcinoma and is Antibody Dependent

Conklin, Chris M.J.; Craddock, Kenneth J.; Have, Cherry L.; Laskin, Janessa; Couture, Christian; Ionescu, Diana N.

doi:10.1097/jto.0b013e318274a83e

Cited by 175 publications

(127 citation statements)

References 29 publications

(45 reference statements)

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“…42,43 In fact, a novel ALK fusion gene (KIF5B-ALK) was discovered following detection using an immunohistochemistry-based method. 15 Differences in antibody staining intensity have also been reported, 28,34 which is validated by the data presented here, with the 5A4 and D5F3 clones showing higher staining intensity than the ALK1 clone.…”

Section: Discussionsupporting

confidence: 70%

“…These data reveal that ALK rearrangements occurred in a small subset (approximately 1%) of lung adenocarcinomas (or NSCLC with an adenocarcinoma component) in an Australian population with resected lung cancer. Although ALK rearrangements have been reported to occur in a range of 0.4-15% of NSCLC, 7,17 the frequency of ALK rearrangements in comparable populations from the United States (8/305;3%) 21 and Canada (3/273;1%) 34 is similar suggesting an ascertainment bias in many other series. However, we cannot exclude geographical variations or differential incidence in early vs advanced disease as an explanation for the low frequency of ALK rearrangements observed in our cohort.…”

Section: Discussionmentioning

confidence: 94%

“…27,37 However, many subsequent studies reported that ALK immunohistochemistry is a highly sensitive method with a significant correlation with ALK FISH using a number of antibodies including the ALK1, 5A4 and D5F3 clones. 15,19,28,31,34,[38][39][40][41] Apart from our study, only one prior group has investigated the performance of all three antibodies in the same patient population, 34 in which they found a very similar incidence of ALK rearrangement (1%) and one false-negative result using the ALK1 antibody. Many studies have reported ALK immunohistochemistry as a useful method for confirming ALK translocation by FISH.…”

Section: Discussionmentioning

confidence: 94%

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Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

et al. 2013

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Rearrangements of anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) define a molecular subgroup of tumors characterized clinically by sensitivity to ALK tyrosine kinase inhibitors such as crizotinib. Although ALK rearrangements may be detected by reverse transcriptase-PCR, immunohistochemistry or fluorescence in situ hybridization (FISH), the optimal clinical strategy for identifying ALK rearrangements in clinical samples remains to be determined. We evaluated immunohistochemistry using three different antibodies (ALK1, 5A4 and D5F3 clones) to detect ALK rearrangements and compared those with FISH. We report the frequency and clinicopathologic features of lung cancers harboring ALK translocations in 594 resected NSCLCs (470 adenocarcinomas; 83 squamous carcinomas, 26 large cell carcinomas and 15 other histological subtypes) using a tissue microarray approach. We identified an ALK gene rearrangement in 7/594 cases (1%) by FISH and all anti-ALK antibodies correctly identified the seven ALK-positive cases (100% sensitivity), although the intensity of staining was weak in some cases. These data indicate that the use of antibodies with high sensitivity and avidity to ALK may provide an effective pre-screening technique to complement the more expensive and labor-intensive approach of ALK FISH testing.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

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Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

et al. 2013

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“…3 Our study is the larger of only two studies that have undertaken a direct comparison of the three most commonly used commercially available antibodies and FISH, with the only other study of this kind examining 377 cases. 4 The findings of our study together with the results of these and other studies have recently been compiled in the 'IASLC atlas of ALK testing in lung Cancer' 5 and are consistent in demonstrating good sensitivity and excellent specificity of IHC when used with appropriate protocols for ALK detection.…”

Section: Response To Mahesupporting

confidence: 84%

Response to Mahe

Cooper

Solomon

2014

Modern Pathology

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“…Comparing with the ALK immunohistochemistry, which is a reliable screening tool for the identification of ALK rearrangement, ALK immunohistochemistry assay showed 66-100% sensitivity and 63-100% specificity using various antibody systems. 36 Therefore, we recommend RET and ROS1 immunohistochemistry as a possible adjunctive diagnostic tool for the detection of RET and ROS1 rearrangements in FFPE tissues.…”

Section: Se Lee Et Almentioning

confidence: 99%

Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

et al. 2015

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The success of crizotinib in ALK-positive patients has elicited efforts to find new oncogenic fusions in lung cancer. These efforts have led to the discovery of novel oncogenic fusion genes such as ROS1 and RET. However, the molecular and clinicopathologic characteristics associated with RET or ROS1 fusion, compared with ALK fusion-positive lung cancer, remain unclear. We accordingly analyzed the clinicopathologic characteristics of RET-and ROS1-fusion-positive lung adenocarcinomas. We further performed immunohistochemistry and fluorescence in situ hybridization analysis (FISH) in 15 cases of RET and 9 cases of ROS1 fusion tumors by identified NanoString's nCounter screening. RET fusion-positive patients were younger in age, never-smokers, and in early T stage; ROS1 fusion-positive patients had a higher number of never-smokers compared with patients with quintuple-negative (EGFR À /KRAS À /ALK À /ROS1 À /RET À ) lung adenocarcinoma. Histologically, RET and ROS1 fusion tumors share the solid signet-ring cell and mucinous cribriform pattern, as previously mentioned in the histology of ALK fusion tumors. Therefore, it can be presumed that fusion gene-associated lung adenocarcinomas share similar histologic features. In immunohistochemistry, the majority of 15 RET and 9 ROS1 fusion-positive cases showed positivity of more than moderate intensity and cytoplasmic staining for RET and ROS1 proteins, respectively. In FISH, the majority of RET and ROS1 rearrangement showed two signal patterns such as one fusion signal and two separated green and orange signals (1F1G1O) and an isolated 3 0 green signal pattern (1F1G). Our study has provided not only characteristics of fusion gene-associated histologic features but also a proposal for a future screening strategy that will enable clinicians to select cases needed to be checked for ROS1 and RET rearrangements based on clinicohistologic features.

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Immunohistochemistry is a Reliable Screening Tool for Identification of ALK Rearrangement in Non–Small-Cell Lung Carcinoma and is Antibody Dependent

Abstract: IHC is a reliable screening tool for identification of ALK rearrangement in NSCLC and is antibody dependent. D5F3 (Cell Signaling) and 5A4 (Novocastra) can be used with FISH for identification of IHC-positive cases to reduce screening costs.

Cited by 175 publications

References 29 publications

Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

Response to Mahe

Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

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