Immunohistochemical Profiling of ALK Fusion Gene–Positive Adenocarcinomas of the Lung

Sakai, Yasuhiro; Nakai, Tokiko; Ohbayashi, Chiho; Imagawa, Naoko; Yanagita, Emmy; Satake, Rumiko; Nitta, Atsushi; Kajimoto, Kazuyoshi; Sakuma, Takashi; Itoh, Tomoo

doi:10.1177/1066896913489345

Cited by 18 publications

(8 citation statements)

References 39 publications

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“…Our diagnosis of SqCC was confirmed by p40 immunostaining, which is useful and highly specific for the diagnosis of SqCC [5, 6]. Additionally, in our case, the results of the ALK detection test were concordant between IHC staining and FISH.…”

Section: Discussionsupporting

confidence: 67%

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

et al. 2017

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BackgroundAlthough anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown.Case presentationWe discuss a 52-year-old Japanese-Brazilian woman without a history of smoking who was referred to our hospital for evaluation of severe left back pain and a left hilar mass observed on a chest radiograph. The patient was eventually diagnosed on the basis of computed tomography, pathological, and immunohistochemical findings as having Stage IV lung SqCC. First-line treatment with palliative radiotherapy and systemic chemotherapy with cisplatin plus vinorelbine was administered, but was not effective. ALK testing was subsequently performed, revealing positive ALK expression and gene rearrangement. Alectinib therapy was then initiated, which resulted in a gradual, but substantial reduction in tumor size.ConclusionsTo the best of our knowledge, this is the first case report to discuss the successful management of ALK-rearranged lung SqCC with alectinib. We propose that molecular testing for driver mutations should be considered in young patients with a light or no smoking history, even if the histological findings correspond with SqCC, and alectinib therapy represents a reasonable option in cases of ALK-rearranged lung SqCC.

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Section: Discussionsupporting

confidence: 67%

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

et al. 2017

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“…None of the ADCs in their study expressed desmoglein 3 and CK5. Although Brown’s study demonstrated an optimal performance of the desmoglein 3 plus CK5 in subtyping SqCC, a recent study by Sakai et al showed that desmoglein 3 was also variably expressed by a subset of lung ADCs [30]. Sethi et al have reported that the combination of TTF1 and Napsin A had 100% sensitivity and specificity in ADC, and the combination of p63 and CK5 had 100% sensitivity and specificity in SqCC [27].…”

Section: Discussionmentioning

confidence: 99%

The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non–small cell lung cancer

Zhang

Sakowski

et al. 2014

Human Pathology

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Summary In lung cancer, targeted therapies depend on accurate histological subclassification of the tumor. The majority of lung cancers can be subclassified based on hematoxylin and eosin staining; however, classification may be difficult in small biopsies. In this study, we investigated the utility of a newly developed triple marker (combination of TTF1/Napsin A/p40) and compared the sensitivity and specificity of this novel marker with individual markers in the subclassification of non–small cell lung carcinomas. Lung cancer tissue microarrays were constructed using surgical resection material from the Johns Hopkins Hospital. They included 77 adenocarcinomas (ADCs), 77 squamous cell carcinomas (SqCCs), and 46 cases of metastatic lung ADCs. Immunostaining patterns of all markers were scored semi-quantitatively and compared. In ADCs, the sensitivity and specificity of the triple marker were 93.5% and 77.5%, respectively. The sensitivity and specificity of TTF1 and Napsin A were 85.7% and 75.0%, and 89.6% and 90.0%. In SqCCs, the sensitivity and specificity of the triple marker were 88.3% and 92.5%, while the p40, p63 and CK5/6 showed 80.5% and 90.0%; 93.5% and 80.0%; and 89.6% and 80.0%. In addition, the sensitivity and specificity of the triple marker in metastatic ADCs showed 71.7% and 73.5%, respectively. Our triple marker (combination of TTF1/Napsin A/p40) showed a similar sensitivity and specificity for the subclassification of NSCLC when compared to individual markers. Our study not only demonstrates a useful combination of immunomarkers but also optimally conserves tissue for molecular marker testing.

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“…Although these molecular diagnostic markers were precise and contributed to targeted therapies, most of the studies used EGFR and K-ras mutations to classify the subtypes of lung adenocarcinoma. An additional factor that must be considered is that EML4–ALK fusions were detected in only about 5% of lung adenocarcinoma, and it was mutually exclusive to other EGFR mutations and K-ras mutations [43]. These problems were further compounded by the fact that, molecular testing for these markers was complex and not easy to perform.…”

Section: Discussionmentioning

confidence: 99%

The High Diagnostic Accuracy of Combined Test of Thyroid Transcription Factor 1 and Napsin A to Distinguish between Lung Adenocarcinoma and Squamous Cell Carcinoma: A Meta-Analysis

Li¹,

Li²,

Yin³

et al. 2014

PLoS ONE

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BackgroundAccurate classification of non-small cell lung cancer (NSCLC) using morphological features has several limitations. However, the use of thyroid transcription factor 1 (TTF-1) and Napsin A as markers for the identification of various subtypes of NSCLC has shown promise. This meta-analysis was designed to evaluate the diagnostic value of combined TTF-1 and Napsin A test to distinguish lung adenocarcinoma from squamous cell carcinoma.MethodsThe Medline, EMBASE and Web of Science databases were searched, along with the reference lists of relevant articles (up to May 4, 2014). Ten studies containing 1,446 subjects were identified. The sensitivity, specificity, diagnostic odds ratio (DOR) and area under the summary receiver operating characteristics curve (AUC) were calculated to estimate the combined diagnostic value of TTF-1 and Napsin A.ResultsThe pooled sensitivity and specificity were 0.76 (95% CI: 0.69–0.83) and 1.00 (95% CI: 0.92–1.00), respectively. The positive and negative likelihood ratios were 877.60 (95% CI: 8.40–91533.40) and 0.24 (95% CI: 0.18–0.32). The DOR was 3719 (95% CI: 33–414884). The AUC was 0.92 (95%CI: 0.89–0.94). The patient's location was a source of heterogeneity for sensitivity. The patient's location, the study's sample size and the threshold used to determine positive staining were consistently found to be sources of heterogeneity for specificity in subgroup analyses and meta-regression.ConclusionsThe combined test of TTF-1 and Napsin A presents a promising alternative method, useful to distinguish between lung adenocarcinoma and squamous cell carcinoma.

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Immunohistochemical Profiling of ALK Fusion Gene–Positive Adenocarcinomas of the Lung

Cited by 18 publications

References 39 publications

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non–small cell lung cancer

The High Diagnostic Accuracy of Combined Test of Thyroid Transcription Factor 1 and Napsin A to Distinguish between Lung Adenocarcinoma and Squamous Cell Carcinoma: A Meta-Analysis

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