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

Selinger, C.I.; Rogers, Toni-Maree; Russell, Prudence A.; O’Toole, Sandra A.; Yip, Po Yee; Wright, Gavin; Wainer, Zoe; Horvath, Lisa G.; Boyer, Michael; McCaughan, Brian C.; Kohonen‐Corish, Maija; Fox, Stephen B.; Cooper, Wendy A.; Solomon, Benjamin

doi:10.1038/modpathol.2013.87

Cited by 132 publications

(112 citation statements)

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“…However, it is expensive, laborious, and requires specialized fluorescence microscopy equipment. 28 In contrast, immunohistochemistry is available in most laboratories and offers more advantages in terms of cost-effectiveness. There have been few reports on the correlation between FGFR2 amplification and protein overexpression by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival

et al. 2016

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FGFR2 gene amplification, and resulting FGFR2 protein overexpression, is rare in gastric cancer patients, and development of an accurate and widely available method for mass screening to identify patients who may respond to treatment with fibroblast growth factor receptor (FGFR) inhibitors is important. We first screened 312 gastric cancer patients with known copy number variations by FGFR2b immunohistochemistry using FPR2-D, an isoformspecific antibody. Next, we performed immunohistochemistry on tissue microarrays from 1574 gastric cancer patients. Selected cases were analyzed for FGFR2 amplification by FISH. In addition, FGFR2b overexpression was studied in 88 matched primary and metastatic gastric cancers. In the first cohort, FGFR2b immunohistochemistry results correlated very well with those of copy number variation (r = 0.79) and FISH (r = 1.0). In total, FGFR2b overexpression was identified in 73 of 1974 gastric cancers (4%). The concordance between immunohistochemistry and FISH was extremely high; all 2+ and 3+ cases identified by immunohistochemistry were FGFR2 amplified. In the matched primary and metastatic gastric cancer pairs, the positivity and percentage of positive tumor cells were significantly higher in metastatic gastric cancers than in primary gastric cancers (8% vs 3% and 75% vs 47%, respectively; Po0.001). FGFR2b overexpression was significantly more frequent in gastric cancers with diffuse subtype (P = 0.01) and higher N stage (P = 0.006). FGFR2b overexpression with H-score ≥ 150 were independent prognostic factors for overall survival with hazard ratio of 1.836 (95% confidence interval, 1.034-3.261; P = 0.038). FGFR2b positivity in immunohistochemistry was strongly correlated with FGFR2 amplification. Given the low frequency of FGFR2 amplification in gastric cancers, FGFRb2 immunohistochemistry is an accurate screening tool to detect FGFR2 amplification, and both primary and metastatic gastric cancer tissues should be tested to select gastric cancer patients for treatment with FGFR2 inhibitors. Gastric cancer is the second most common cause of cancer-related deaths worldwide, and the prognosis of advanced gastric cancer is still poor. 1 Several large-scaled clinical trials have failed to demonstrate survival benefits of targeted therapeutic agents in patients with metastatic gastric cancer. Nevertheless, the REGARD trial demonstrated significantly longer progression-free survival of gastric cancer patients treated with ramucirumab, a monoclonal antibody against vascular endothelial growth factor receptor 2, compared with that of patients in the placebo group. 2 This was the first trial to demonstrate a meaningful benefit for a monotherapy in metastatic gastric cancer. The RAINBOW trial, which compared the efficacy of paclitaxel with or without ramucirumab in second-line chemotherapy, showed prolonged

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Section: Discussionmentioning

confidence: 99%

FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival

et al. 2016

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“…may occur due to variant forms of EML4-ALK rearrangements and/or RNA editing abnormalities resulting in intron changes that cannot be detected by FISH [4]. Several groups have published on the comparative accuracy of FISH, IHC, and NGS; however, the sensitivity, specificity, and cost of these modalities have not been directly compared in large prospective trials to date [3][4][5][6]. We report here two cases with clinically false positive FISH results.…”

Section: Introductionmentioning

confidence: 92%

Fishing for Precision in ALK-Rearranged Non-Small-Cell Lung Cancers

Le¹,

Peters²

2015

Oncology and cancer case reports

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“…Screening strategies require confirmation by a more accurate testing method and the relatively low positive predictive values support confirmation by FISH testing as outlined in our paper. 1 The optimal diagnostic algorithm to detect ALK in clinical samples is still evolving and will likely be influenced not only by test sensitivity and specificity but also by local expertise and cost effectiveness. Our study and others support the inclusion of IHC within this algorithm.…”

Section: Response To Mahementioning

confidence: 99%