Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens

Kim, Mi Jin; Shin, Hyeong Chan; Shin, Kyeong Cheol; Ro, Jae Y.

doi:10.1016/j.anndiagpath.2012.07.006

Cited by 74 publications

(77 citation statements)

References 27 publications

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“…Also, Terry et al (2010) report that p63 is the single best marker to separate ADC from SCC, with the sensitivity of 84% and the specificity of 85%. Further analysis identifies p63, TTF1, CK5/6, and Napsin A as the optimal panel to isolate ADC from SCC (Kim et al, 2013). Novel biomarkers (miR-93, miR-205, miR-221, and let-7e) for differential diagnosis and prognosis of NSCLC subtypes are also found by means of identifying differential expression profiles of miRNAs in ADC and SCC (Zhang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

Liu¹,

Yang²,

Shi³

2014

Genet. Mol. Res.

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ABSTRACT. Non-small cell lung carcinoma, NSCLC, accounts for 80-85% of lung cancers. NSCLC can be mainly divided into two types: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The purpose of our study was to identify and differentiate the pathogenesis of ADC and SCC at the molecular level. The gene expression profiles of ADC and SCC were downloaded from Gene Expression Omnibus under accession No. GSE10245. Accordingly, differentially expressed genes (DEGs) were identified by the limma package in R language. In addition, DEGs were functionally analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 4124 DEGs were identified, including CDK1, CDK2, CDK4, and SKP2. The DEGs were mainly involved in 16 pathways related to cell proliferation, cell signal transduction and metabolism. We conclude that the molecular mechanisms of ADC and SCC are considerably different, and that they are involved in immune response, cell signal transduction, metabolism, cell division, and cell proliferation. Therefore, the two diseases should be treated differently. This study offers new insight into the diagnosis and therapy of these two types of lung cancer.

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Section: Introductionmentioning

confidence: 99%

Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

Liu¹,

Yang²,

Shi³

2014

Genet. Mol. Res.

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“…TTF-1 has been reported to be one of several markers differentiating adenocarcinoma from squamous cell carcinoma of the lung (13). The antibodies were visualized by Alexa Fluor 488-labeled goat anti-mouse IgG and Alexa Fluor 594-labeled goat antirabbit IgG antibody (Life Technologies), respectively.…”

Section: Immunohistochemistry and Immunofluorescence Stainingmentioning

confidence: 99%

Alpha-Smooth Muscle Actin (ACTA2) Is Required for Metastatic Potential of Human Lung Adenocarcinoma

Lee

Park

Lee

et al. 2013

Clinical Cancer Research

120

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Purpose: Metastatic relapse of primary lung cancer leads to therapeutic resistance and unfavorable clinical prognosis; therefore, identification of key molecules associated with metastatic conversion has significant clinical implications. We previously identified a link between early brain metastasis of lung adenocarcinoma and amplification of the a-smooth muscle actin (ACTA2) gene. The aim of present study was to investigate the prognostic and functional significance of ACTA2 expression in cancer cells for the metastatic potential of lung adenocarcinomas.Experimental Design: ACTA2 expression was analyzed in tumor cells from 263 patients with primary lung adenocarcinomas by immunohistochemistry, and was correlated with clinicopathologic parameters. The expression of ACTA2 in human lung adenocarcinoma cells was modulated with short hairpin RNAs (shRNA) and siRNAs specifically targeting ACTA2.Results: The patients with lung adenocarcinomas with high ACTA2 expression in tumor cells showed significantly enhanced distant metastasis and unfavorable prognosis. ACTA2 downregulation remarkably impaired in vitro migration, invasion, clonogenicity, and transendothelial penetration of lung adenocarcinoma cells without affecting proliferation. Consistent with the in vitro results, depletion of ACTA2 in human lung adenocarcinoma PC14PE6 cells significantly reduced their metastatic potential without altering their tumorigenic potential. Expression of c-MET and FAK in lung adenocarcinoma cells was also reduced by ACTA2-targeting siRNAs and shRNAs, and was accompanied by a loss of mesenchymal characteristics.Conclusions: These findings indicate that ACTA2 regulates c-MET and FAK expression in lung adenocarcinoma cells, which positively and selectively influence metastatic potential. Therefore, ACTA2 could be a promising prognostic biomarker and/or therapeutic target for metastatic lung adenocarcinoma.

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“…The treatment effects vary in LUSC and LUAD patients. 3 With the rapid development of the targeted therapies for NSCLC, more efficient treatments are available for the both NSCLC subtype. However, to choose treatments, especially targeted therapies and combination of interventions, we need accurate sub-typing between them.…”

Section: Introductionmentioning

confidence: 99%

“…However, to choose treatments, especially targeted therapies and combination of interventions, we need accurate sub-typing between them. 3 Currently, the most widely used method to distinguish between LUAD and LUSC is hematoxylin-eosin (HE) staining of the tumor tissue sections observed under a light microscope. However, due to the reasons such as unclear structures in tumors and small biopsies with a limited number of tumor cells, by using only HE staining, it is difficult to make the precise diagnosis on LUAD and LUSC.…”

Section: Introductionmentioning

confidence: 99%

Classifying Lung Adenocarcinoma and Squamous Cell Carcinoma using RNA-Seq Data

Huang¹,

Chen²,

Wang³

2017

Cancer Stud Mol Med Open J

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Background: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are two primary subtypes of non-small cell lung carcinoma (NSCLC). Currently, the most widely used method to discriminate between LUAD and LUSC is hematoxylin-eosin (HE) staining. However, this method sometimes is unable to make the precise diagnosis on LUAD or LUSC. More accurate diagnostic approaches are highly desired. Methods: We propose to use gene expression profile to discriminate NSCLC patient's subtype. We leveraged RNA-Seq data from The Cancer Genome Atlas (TCGA) and randomly split the data into training and testing subsets. To construct classifiers based on the training data, we considered three methods: logistic regression on principal components (PCR), logistic regression with LASSO shrinkage (LASSO), and kth nearest neighbors (KNN). Performances of classifiers were evaluated and compared based on the testing data. Results: All gene expression-based classifiers show high accuracy in discriminating LUSC and LUAD. The classifier obtained by LASSO has the smallest overall misclassification rate of 3.42% (95% CI: 3.25%-3.60%) when using 0.5 as the cutoff value for the predicted probability of belonging to a subtype, followed by classifiers obtained by PCR (4.36%, 95% CI: 4.23%-4.49%) and KNN (8.70%, 95% CI: 8.57%-8.83%). The LASSO classifier also has the highest average area under the receiver operating characteristic curve (AUC) value of 0.993, compared to PCR (0.987) and KNN (0.965). Conclusions: Our results suggest that mRNA expressions are highly informative for classifying NSCLC subtypes and may potentially be used to assist clinical diagnosis.

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Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens

Cited by 74 publications

References 27 publications

Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

Alpha-Smooth Muscle Actin (ACTA2) Is Required for Metastatic Potential of Human Lung Adenocarcinoma

Classifying Lung Adenocarcinoma and Squamous Cell Carcinoma using RNA-Seq Data

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