EGFR and KRAS mutations in metastatic lung adenocarcinomas

Munfus-McCray, Delicia; Harada, Shuko; Adams, Christina; Askin, Frederic B.; Clark, Douglas P.; Gabrielson, Edward; Li, Qing Kay

doi:10.1016/j.humpath.2010.12.011

Cited by 50 publications

(45 citation statements)

References 30 publications

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“…Among them, adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are predominate histological subtypes [1] and [2]. Recently, therapeutic strategy has changed from traditional tumor stage–based approaches to histomorphology and genetic mutation–guided targeted therapies [3], [4], [5], [6] and [7]. The discovery of epidermal growth factor receptor (EGFR) gene mutations in ADC and the subsequent success in targeting these tumors with tyrosine kinase inhibitors highlight the critical role of accurate subclassification of the tumor [8], [9], [10] and [11].…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Before February 2013, Sanger sequencing was used for detection of EGFR mutations within exons 18-21 and pyrosequencing was used to detect mutations at codons 12 and 13 of the KRAS gene and codon 600 of the BRAF genes as previously described [21][22][23] . Reflex fluorescence in situ hybridization testing was performed to detect ALK translocations if no mutations were identified in KRAS or EGFR.…”

Section: Molecular Testingmentioning

confidence: 99%

Molecular Alterations in Patients with Pulmonary Adenocarcinoma Presenting with Malignant Pleural Effusion at the First Diagnosis

et al. 2017

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Objectives: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. Study Design: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression. Results: We identified 18 patients (9 males and 9 females). Micropapillary and/or solid adenocarcinoma type features predominated among cytologic specimens (n = 15), while acinar patterns predominated in controls. Survival was not significantly different from that of the control group (mean 13.8 vs. 13.9 months, respectively; p = 0.61). Ten (55%) cases had mutations in EGFR (n = 6; 60%), KRAS (n = 3; 30%), or ALK translocation (n = 1; 10%). No mutations were identified in BRAF, AKT, ERBB2, NRAS, or PIK3CA (tested in 7 patients). Patients positive for the tested mutations had a better overall survival than patients negative for the mutations (mean survival 16.2 vs. 6.05 months, respectively; p = 0.006, log-rank test). Ten (84%) control patients were positive for mutations in EGFR (n = 5; 42%), KRAS (n = 4; 34%), or ALK translocation (n = 1; 8.4%). Conclusion: In our series, a micropapillary-like and solid-like morphology, common in cytologic specimens, and alterations in EGFR were the most frequent identifiable molecular changes.

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“…26 KRAS and EGFR mutations can be discordant between primary and metastatic tumors, suggesting that mutation status of both primary and metastatic lesions need to be established before the initiation of therapy. 27 In the setting of multifocal primary adenocarcinoma, combining the results for the EGFR and KRAS mutation status allows the clonality status to be determined for most patients. 28 v-Ki-ras2 KIRSTEN RAT SARCOMA VIRAL ONCOGENE HOMOLOG The ras proteins or p21ras belong to the small guanosine triphosphatase superfamily, of which KRAS, HRAS, and NRAS are the 3 best known among various members.…”

Section: Egfr Mutations and Morphology (Clinical And Histologic Corrementioning

confidence: 99%

Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine

Raparia

Villa

DeCamp

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the socalled driver mutations, which may serve as ''druggable'' therapeutic targets. Thus, development of personalized approaches for the treatment of non-small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors.Objective.-To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC.Data Sources.-Peer-reviewed published literature and personal experience.Conclusions.-There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.(Arch Pathol Lab Med. 2013;137:481-491; doi: 10.5858/ arpa.2012-0287-RA) L ung cancer is the leading cause of cancer-related mortality in both men and women in the United States. It is projected that in 2012, lung cancer will account for 26% and 29% of cancer-related deaths in the female and male population, respectively.1 Historically, lung cancer has been divided into 2 major categories based on the histologic features and response to conventional therapies, and they include non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma. NSCLC includes 3 cell types (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma), and these can be further divided into various subtypes or variants.2 NSCLC accounts for most (~80%) of the lung cancers, with lung adenocarcinoma being the most common subtype in the United States. Despite significant improvements in radiologic imaging, supportive care, availability of newer antineoplastic agents, and multimodality therapy, the 5-year relative survival rate for lung cancer in the United States remains dismal, that is, at only 16% in 2007 compared to 12% in 1975, thus indicating little improvement in survival rate over a period of 3 decades.

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EGFR and KRAS mutations in metastatic lung adenocarcinomas

Cited by 50 publications

References 30 publications

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

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

Molecular Alterations in Patients with Pulmonary Adenocarcinoma Presenting with Malignant Pleural Effusion at the First Diagnosis

Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine

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