Article

Mucinous Differentiation Correlates with Absence of EGFR Mutation and Presence of KRAS Mutation in Lung Adenocarcinomas with Bronchioloalveolar Features

Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Journal of Molecular Diagnostics (Impact Factor: 4.85). 08/2007; 9(3):320-6. DOI: 10.2353/jmoldx.2007.060182
Source: PubMed

ABSTRACT

Somatic mutations in the epidermal growth factor receptor gene (EGFR) are detected in a subset of lung adenocarcinomas, particularly bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (AWBF), and correlate with clinical response to tyrosine kinase inhibitors (TKIs). In contrast, lung adenocarcinomas refractory to TKIs often have activating mutations in KRAS but lack EGFR mutations. Some adenocarcinomas have mucinous histology, but the clinical and molecular significance of the mucinous pattern is less well studied. We analyzed 43 BAC and AWBF tumors submitted for EGFR mutation testing to identify histopathological features that predicted EGFR or KRAS mutations. EGFR mutations were detected in 14 of 30 (47%) nonmucinous tumors, whereas 0 of 13 mucinous tumors harbored an EGFR mutation (P = 0.003). Missense mutations in KRAS codon 12 were detected in six of seven (86%) mucinous adenocarcinomas but only 3 of 18 (17%) nonmucinous adenocarcinomas (P = 0.003). Thus, in BAC/AWBF mucinous differentiation was significantly correlated with the absence of EGFR mutation and presence of KRAS mutation, suggesting that mucinous BACs/AWBFs are unlikely to respond to TKIs. Therefore, our data suggest that EGFR sequence analysis could be avoided in BAC/AWBF when true mucinous morphology is identified, avoiding the associated testing costs.

Full-text preview

Available from: ncbi.nlm.nih.gov
  • Source
    • "KRAS mutations are observed in close to 30% of adenocarcinomas of the lung, but are uncommon in SQCC (about 5%) [138]. KRAS mutations are found in majority of mucinous adenocarcinomas [139, 140]. Point mutations at codons 12, 13, or 61 in the KRAS oncogene lead to constitutive activation of KRAS protein via changes at the GTP binding domain, which prevents the conversion of GTP to GDP. "
    [Show abstract] [Hide abstract] ABSTRACT: Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review.
    Full-text · Article · Mar 2014 · Oncotarget
  • Source
    • "On the other hand, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) is a critical downstream effector of the EGFR pathway. K-RAS mutations are associated with intrinsic tyrosine kinase inhibitor (TKI) resistance in patients with lung cancer [7,8]. Thus, molecular diagnosis of these mutations is increasingly important in making therapeutic decisions. "
    [Show abstract] [Hide abstract] ABSTRACT: Although epidermal growth factor receptor (EGFR) inhibitor treatment showed modest response in several clinical trials in esophageal squamous cell carcinoma (ESCC) patients, it has been reported that the frequency of EGFR mutations varied largely. The aim of this study was to investigate the existence of EGFR mutations in Chinese esophageal squamous cell carcinomas. Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 127 randomly selected Chinese patients with ESCC. The most common EGFR mutations, including in-frame deletions in exon 19 and base substitutions in exon 21, were detected by denaturing high performance liquid chromatography (DHPLC) and direct sequencing simultaneously. K-RAS mutations in codons 12 and 13 were detected by direct sequencing. In this study, L858R missense mutations of the EGFR gene were found in 8 out of 127 patients (6.3%) by DHPLC but no mutation was observed by direct sequencing. In addition, K-RAS mutation was detected in 2 out of 127 (1.6%) patients by direct sequencing. The incidence of EGFR mutations was relatively high using DHPLC method but no mutation with direct sequencing in Chinese ESCC patients.
    Full-text · Article · Oct 2013 · World Journal of Surgical Oncology
  • Source
    • "Im Gegensatz dazu konnte bei muzinösen Adenokarzinomen bislang noch keine EGFR-Mutation nachgewiesen werden. Muzinöse Karzinome zeigen jedoch deutlich häufi ger Mutationen des KRAS-Gens141516. Bei Plattenepithelkarzinomen wurden EGFR-Genmutationen nur in einem geringen Prozentsatz (1–4 %) gefun- den [17]. "
    [Show abstract] [Hide abstract] ABSTRACT: Patients with stage IIIB and IV non-small cell lung carcinoma (NSCLC) harboring an activating mutation of the Epidermal Growth Factor Receptor (EGFR) Gene should be treated first-line with Gefitinib, an EGFR tyrosine kinase inhibitor (TKI). EGF receptor mutations are most common in adenocarcinomas, especially non-mucinous type, rare in squamous cell carcinomas and sarcomatoid carcinomas, and do not occur in neuroendocrine carcinomas. Therefore, the Pulmonary Pathology Working Group of the Austrian Society of Pathology, after intense discussions and in consensus with Oncologists and Pulmonologists, recommends a priori EGFR mutation analysis for all cases of adenocarcinoma, and for all other NSCLC upon clinical request. This will markedly reduce waiting time for those patients, which most likely will have the greatest benefit from EGFR TKI therapy.
    Full-text · Article · May 2011 · Wiener klinische Wochenschrift
Show more