Mucinous micropapillary pattern in lung adenocarcinomas: a unique histology with genetic correlates

Kamata, Tsugumasa; Yoshida, Akihiko; Shiraishi, Kouya; Furuta, Koh; Kosuge, Tomoo; Watanabe, Shun; Asamura, Hisao; Tsuta, Koji

doi:10.1111/his.12763

Cited by 15 publications

(8 citation statements)

References 33 publications

(42 reference statements)

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“…A more pragmatic alternative would be to screen with IHC and to test all patients with a higher probability (non-smokers, younger age) of ALK rearrangements with FISH. It should be stressed that also histological features, as the recently described mucinous-cribriform/papillary histologic growth pattern, are strongly correlated with the presence of fusion genes [ 73 , 74 ] and thus can be used as a criteria for ALK-testing.…”

Section: Discussionmentioning

confidence: 99%

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

et al. 2016

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BackgroundIdentification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.MethodsALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.ResultsALK rearrangements were detected in 1.7 % in the complete cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %) tumors showed high ALK gene expression (≥ 6 AU) and of them only three were positive by either FISH or IHC.ConclusionThe overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2646-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

et al. 2016

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“…analyses, mucinous variant of micropapillary carcinoma tended to be more aggressive compared with non-mucinous micropapillary cacrcinoma. However, the prognostic value of the mucinous variant was not shown to be statistically signifi cant in a study by Kamata et al [43].…”

Section: Mucinous Variant Of Micropapillary Carcinoma: In Survivalmentioning

confidence: 90%

“…In LADC, HER2 mutation is more common in females [70]. Micropapillary LADC, particularly mucinous type, showed higher incidences of HER2 and ALK mutations with lower incidences of EGFR mutation in two studies [58,71]. Patients with tumors harboring HER2 mutations have been shown in clinical trials to respond to several types of targeted therapies (i.e.…”

Section: Most Common Mutations and Translocations: Variablementioning

confidence: 99%

Micropapillary Adenocarcinoma of the lung: Recent updates and literature review

Monroig-Bosque¹,

Shehabeldin²,

Ro³

2019

Arch Pulmonol Respir Care

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Background: Lung cancer is the most frequent cause of cancer-related death worldwide. For adenocarcinomas, histological subtyping is typically performed (e.g. lepidic, acinar, papillary, micropapillary, and solid), as suggested by the World Health Organization. Among these, micropapillary carcinoma has been a focus of signifi cant research in recent years, as it is the newest subtype and has the worst prognosis. Herein, we summarize the most relevant fi ndings of this morphological variant in detail with anecdotal experience and a review of the published literature. Results:A PubMed query for "adenocarcinoma of the lung" resulted in 177 full-length articles. The reviewed articles were grouped by category as follows: 1) history (2002)(2003)(2004)(2005)(2006)(2007)(2008), 2) morphologic/ diagnostic features, 3) prognostic implications, 4) molecular features and targeted therapies, and 5) radiologic/imaging fi ndings. Our results consistently showed that a micropapillary carcinoma component is associated with poor prognosis in patients with lung adenocarcinoma. Additionally, our investigation highlighted the fact that there have been no studies validating the diagnostic/morphologic criteria that should be used to achieve an accurate diagnosis of micropapillary lung adenocarcinoma. Nonetheless, we present that molecular studies continue to emerge, and there is signifi cant opportunity for targeted therapeutic options that remains to be explored in depth. Conclusion:Our review offers insight into novel studies focused on micropapillary lung adenocarcinoma. We present the potential for new research opportunities, particularly molecular studies aimed at determining targeted treatment options.

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“…Gerektiği zaman bu panele müsin boyası eklenebilir (8-10). (18,19). Son yıllarda, ErbB2/ErbB3 yolağındaki regülasyon bozukluğu, özellikle KRAS mutasyonu pozitif müsinöz patern gösteren AK'larda yeni bir onkojenik özellik olarak gösterilmiştir (20).…”

Section: Solid Adenokarsinomunclassified

Changes in the classification of lung adenocarcinoma

Gümürdülü¹,

Nart²

2019

JCurrPath

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Mucinous micropapillary pattern in lung adenocarcinomas: a unique histology with genetic correlates

Abstract: Mucinous micropapillary pattern is an under-recognized unique growth associated significantly with HER2 mutation and ALK rearrangement.

Cited by 15 publications

References 33 publications

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

Micropapillary Adenocarcinoma of the lung: Recent updates and literature review

Changes in the classification of lung adenocarcinoma

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