کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2141882 1088301 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Frequency and clinicopathologic correlates of KRAS amplification in non-small cell lung carcinoma
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Frequency and clinicopathologic correlates of KRAS amplification in non-small cell lung carcinoma
چکیده انگلیسی

BackgroundCharacterization of the non-small cell lung cancer (NSCLC) genome has suggested that KRAS amplification is one of the commonest molecular abnormalities in NSCLC. However, the prevalence and clinicopathologic significance of KRAS amplification, and its relationship with KRAS activating mutations have not been well-defined. The purpose of this study was to establish the prevalence of KRAS amplification in two separate, large NSCLC cohorts, to define the clinicopathologic features of KRAS-amplified NSCLC in a single uniformly treated cohort, and to investigate the interplay between KRAS amplification and KRAS mutation.MethodsFluorescence in situ hybridization was utilized to detect KRAS amplification on tissue microarrays constructed from a Swiss cohort of 538 NSCLCs and a series of 402 patients with NSCLC treated in a single institution in New York. DNA sequencing to detect KRAS codon 12 activating mutations was performed on a subset of tumors. Amplification and mutation status were compared with patient baseline characteristics, tumor characteristics, and overall- and disease-free survival.ResultsThe prevalence of KRAS amplification was 13.7% in the Swiss cohort and 15.1% in the New York cohort. Among adenocarcinomas, KRAS amplification was associated with larger (mean size 2.8 ± 1.8 cm vs. 2.1 ± 1.3 cm, p = 0.003), less well-differentiated tumors (18% vs. 42%, p = 0.004) that were more likely to be invasive (95% vs. 77%, p = 0.004) and to exhibit angiolymphatic invasion (24% vs. 12%, p = 0.04). These differences were statistically significant within the subset of adenocarcinomas harboring activating KRAS mutations, suggesting a synergistic relationship between amplification and mutation. No significant association between KRAS amplification and nodal metastasis or survival was seen.ConclusionsKRAS amplification is a common molecular alteration in NSCLC, characterizing ∼15% of tumors. This alteration is associated with indicators of local aggressiveness, and may act synergistically with KRAS mutations to promote tumor progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Lung Cancer - Volume 74, Issue 1, October 2011, Pages 118–123
نویسندگان
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