Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma

Jokoji, Ryu; Yamasaki, Takashi; Minami, Seigo; Komuta, Kiyoshi; Sakamaki, Yasushi; Takeuchi, Kengo; Tsujimoto, Masahiko

doi:10.1136/jcp.2010.081166

Cited by 117 publications

(108 citation statements)

References 17 publications

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“…8,13,15,17 Furthermore, our analysis did not identify the cribriform pattern, extracellular mucin, or the 'mucinous cribriform' pattern to be strong predictors for ALK rearrangements in our patient cohort, in contrast to the findings described by others. 15,17 It is unclear whether the discrepancies between our study and those from Japan represent ethnic or other differences between the study populations. In spite of these differences, the solid, micropapillary, and cribriform patterns were all classified as 'high-grade' patterns with increased metastatic potential by a recently proposed histologic grading system for lung adenocarcinomas.…”

Section: Nishino Et Alcontrasting

confidence: 99%

“…In contrast, morphologic analysis of resected primary ALK þ lung adenocarcinomas from a predominantly Asian patient cohort identified acinar-predominant architecture and abundant mucin production as morphologic features significantly associated with ALK rearrangements. 8,13,17 It is unclear whether these conflicting results are due to differences in tumor stage (early vs advanced), specimen source (primary vs metastatic tumor), or ethnicity in the study populations. Furthermore, at least 70% of patients with lung cancer present at an advanced stage with unresectable disease.…”

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confidence: 99%

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Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas

et al. 2012

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Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib. Defining distinctive features of ALK-rearranged (ALK þ ) lung adenocarcinomas may help identify cases that merit molecular testing. However, data describing the morphologic features of ALK þ lung adenocarcinomas are conflicting and are primarily based on analysis of resected primary lung tumors. It is unclear whether the findings from prior studies are applicable to metastatic lung tumors or to small biopsy/ cytology specimens. To address these issues, we examined resection, excision, small biopsy, and cytology cell block specimens from 104 ALK þ and 215 ALKÀ lung adenocarcinomas from primary and metastatic sites. All cases were evaluated for ALK rearrangements by fluorescence in situ hybridization. The predominant histologic subtypes and distinctive cytomorphologic features were assessed in each case. Primary ALK þ lung adenocarcinomas showed a significant association with solid, micropapillary, and papillary-predominant histologic patterns and tumor cells with a signet ring or hepatoid cytomorphology. Among metastatic lung tumors and small biopsy/cytology specimens, the only distinguishing morphologic feature of ALK þ tumors was the presence of signet ring cells. Based on these results, we developed a morphology-based scoring system for predicting ALK rearrangements in lung adenocarcinomas. The scoring system predicted ALK rearrangements in a new cohort of 78 lung adenocarcinomas (29 ALK þ and 49 ALKÀ) with a sensitivity of 88% and a specificity of 45%. In conclusion, ALK þ lung adenocarcinomas have distinctive morphologic features, with signet ring cells showing a significant association with ALK rearrangements irrespective of tumor site (primary vs metastatic) or specimen type. However, morphologic screening alone will not detect a minority of ALK þ lung adenocarcinomas, and the routine use of ancillary studies may be warranted to identify all patients who may benefit from crizotinib treatment.

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Section: Nishino Et Alcontrasting

confidence: 99%

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confidence: 99%

Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas

et al. 2012

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“…EML4-ALK rearrangements occur in adenocarcinomas that often show solid, acinar or signet ring histologic patterns. 18,19 ALK rearrangements have been commonly reported in patients who are younger and never or light smokers and are generally wild type for EGFR and KRAS mutations. 20,21 However, the clinical and pathologic features of ALK-positive NSCLC overlap significantly with ALK-negative NSCLC.…”

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confidence: 99%

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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“…ALK FISH is regarded as the gold standard for confirming ALK rearrangements and in the US, prescription of crizotinib is dependent upon the use of the ALK Break Apart FISH Probe Kit (Abbott Molecular, Inc.) [32]. Good concordance between IHC and FISH results has been reported [33,34]. Therefore, it may be beneficial (easier, quicker, and cheaper) to use IHC to screen for ALK variants in the first instance as a negative ALK IHC test in particular, has a near 100% predictive value for negative FISH testing.…”

Section: Biomarkers In Nsclcmentioning

confidence: 99%

“…It is particularly useful in endoscopically visible tumours [13]. In comparison with the direct smear technique, the Saccomanno brush wash, which brushes cells directly into fixative, has shown better results [33,42].…”

Section: Exfoliative Cytologymentioning

confidence: 99%

Diagnosis and Predictive Molecular Analysis of Non–Small-Cell Lung Cancer in the Africa-Middle East Region: Challenges and Strategies for Improvement

Slavík

Asselah

Fakhruddin

et al. 2014

Clinical Lung Cancer

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Identification of tumour biomarkers provides information on prognosis and guides the implementation of appropriate treatment in patients with many different types of cancer. In nonsmall-cell lung cancer (NSCLC), targeted treatment plans based on biomarker identification are already being utilised in the clinic. However, such predictive molecular testing is not currently a universally employed practice. This is particularly the case in developing countries where lung cancer is increasingly prevalent. In September 2012 and November 2013, a committee of 16 lung cancer experts from Africa and the Middle East met to discuss key issues related to diagnosis and biomarker testing in NSCLC and the implementation of personalised medicine in the region. The committee identified current challenges for effective diagnosis and predictive analysis in Africa and the Middle East. Moreover, strategies to encourage the implementation of biomarker testing were discussed.Ultimately, a practical approach for the effective diagnosis and predictive molecular testing of NSCLC in these regions was derived. Key issues and recommendations arising from the meetings are presented here.Abstract word count: 167 (journal limit: 250)

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Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma

Abstract: EML4-ALK-positive lung adenocarcinoma has a tendency to express a characteristic morphological pattern. The combined use of morphological feature analysis and immunohistochemistry may be a useful and cost effective screening method for EML4-ALK lung adenocarcinoma.

Cited by 117 publications

References 17 publications

Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas

Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas

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

Diagnosis and Predictive Molecular Analysis of Non–Small-Cell Lung Cancer in the Africa-Middle East Region: Challenges and Strategies for Improvement

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