Clinicopathological and prognostic features of surgically resected pathological stage <scp>I</scp> lung adenocarcinoma harboring epidermal growth factor receptor and <scp>K</scp>‐ras mutation

Kaseda, Kaoru; Asakura, Keisuke; Kazama, Akio; Ozawa, Yukihiko

doi:10.1111/1759-7714.12428

Cited by 10 publications

(14 citation statements)

References 47 publications

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“…The prognosis of MIA remains unclear (60). It has been reported that EGFR mutation status has no effect on the prognosis of patients with early stage lung adenocarcinoma (61). However, the present data provide preliminary evidence to support consideration of EGFR mutation status as indication of prognostic stratification in future clinical studies involving MIA.…”

Section: Egfr Mutation Statusmentioning

confidence: 60%

Significance of the epidermal growth factor receptor mutation status and differences among molecular subgroups in surgically resected lung microinvasive adenocarcinoma

et al. 2018

Oncol Lett

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Lung microinvasive adenocarcinoma (MIA) is a newly-defined subtype of early stage non-small cell lung cancer (NSCLC). However, its epidermal growth factor receptor (EGFR) mutation status and clinical significance remain unclear. The present study aimed to determine EGFR mutation characteristics and identify their significance in patients with resected lung MIA. The present study also analyzed clinicopathological differences between EGFR molecular subgroups defined as 19Del and L858R. The present study examined EGFR mutations in 79 consecutive lung MIA resection specimens and compared the differences in clinicopathological features between the EGFR wild-type and mutation groups, as well as between the 19Del and L858R subgroups. EGFR mutations were detected in 60 (75.95%) tumors. The most common mutations were 19Del (28 cases; 35.44%) and L858R (30 cases; 37.97%). Two patients harbored rare mutations and one of them had a concomitant double mutation. EGFR mutations were significantly associated with microinvasion component, thyroid transcription factor 1 (TTF-1) expression, intratumoral fibrosis and inflammatory cell infiltration. Subgroup evaluation indicated that there was a significant association between 19Del and tumor size, maximum diameter of microinvasion, presence of intratumoral fibrosis and inflammatory cell infiltration. Similar associations were observed for the L858R subgroup, and L858R was associated with TTF-1 expression. In particular, 19Del occurred more frequently in MIA with a smaller size, with a smaller microinvasive area, without TTF-1 expression, and lacking intratumoral fibrosis and inflammatory cell infiltration. By contrast, L858R was detected more frequently in MIA with entirely different tumor features. In conclusion, the results of the present study indicated that surgically resected MIA cases harboring different EGFR gene statuses exhibit distinct clinicopathological features. Significant differences in pathological features associated with the tumor microenvironment were identified in MIA with 19Del or L858R mutations. Therefore, the present study proposed that MIA should be classified into molecular subgroups based on EGFR mutation subtypes. The molecular sub-classification should be taken into account for prognostic evaluation and clinical management of MIA.

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Section: Egfr Mutation Statusmentioning

confidence: 60%

Significance of the epidermal growth factor receptor mutation status and differences among molecular subgroups in surgically resected lung microinvasive adenocarcinoma

et al. 2018

Oncol Lett

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“…DFS Seventeen studies with 5,261 patients assessed the relationship between EGFR mutations and DFS, 11 , 13 , 22 , 25 , 29 , 31 , 32 , 34 – 38 , 42 – 44 , 46 , 47 and six studies demonstrated that EGFR mutations positively influenced the DFS of resected NSCLC patients. 13 , 25 , 35 , 42 , 43 , 47 Significant heterogeneity was observed between these studies ( I 2 =72%, p <0.00001; Figure S1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The relationship between EGFR mutations and OS was evaluated based on 26 studies, 11 , 13 , 16 , 19 – 23 , 25 , 27 – 31 , 33 – 40 , 42 – 44 , 47 with 8,100 patients, and seven studies 11 , 13 , 28 , 33 , 35 , 42 , 47 indicated that EGFR mutations were a favorable prognostic factor for OS in resected NSCLC patients. Some heterogeneity was noted between the studies ( I 2 =42%, p =0.008; Figure S4A ).…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a systematic review and meta-analysis

Zhang¹,

Zhu²,

Ding³

et al. 2018

CMAR

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BackgroundThe prognostic value of EGFR and KRAS mutations in resected non-small cell lung cancer (NSCLC) has been reported. However, conflicting results were reported in these studies. The effect of mutations in these two genes in resected NSCLC remains controversial.MethodsWe searched Internet databases for studies reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or KRAS mutations with the prognosis of patients after surgery.ResultsA total of 9,635 patients from 32 studies were included in this analysis. The combined HR for EGFR mutations on DFS was 0.77 (95% CI 0.66–0.90, p=0.001) and on OS was 0.72 (95% CI 0.66–0.80, p<0.00001). In addition, the combined HR for KRAS mutations on DFS was 1.5 (95% CI 1.15–1.96, p=0.002) and on OS was 1.49 (95% CI 1.28–1.73, p<0.00001). Sensitivity analysis, subgroup analysis, and bias analysis proved the stability of the results.ConclusionThe analysis showed that EGFR mutations were significantly associated with DFS and OS. These findings indicated that surgically treated NSCLC patients with EGFR mutations were inclined to exhibit a prolonged DFS and OS. In addition, the results indicated that KRAS mutations predicted worse DFS and OS in patients with resected NSCLC.

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“…It has been observed that lung cancer seen in the non-smoking group is more likely to be younger than the smoker group, and that it is in the subtype of women and adenocarcinoma. KRAS mutation has been reported to be more common in the adenocarcinoma subtype [37]. Smoking specific nitric amines in cigarettes have been shown to induce KRAS gene mutations.…”

Section: Methodsmentioning

confidence: 99%

Determination of Epidermal Growth Factor Receptor (EGFR), KRAS and BRAF Mutation in Non Small Cell Lung Cancers Using Biofilm Chip Based Microarray Technology

Günizi¹,

Özbilim²,

Ozcan³

2019

Int J Respir Pulm Med

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Background: In this study, it vi cell lung carcinoma. Methods: 96 lung resection materials; it was examined for the presence of TNM (The TNM Staging System is based on the extent of the tumor (T), the extent of spread to the lymph nodes (N), and the presence of metastasis (M)) stage, smoking, age, sex, tumor differentiation and EGFR, KRAS and BRAF mutations. Results: Of the 96 patients included in the study, 58 were adenocarcinomas, 30 were squamous cell carcinomas (SCC), and 8 were large cell neuroendocrine carcinomas (LCNEC). While EGFR mutation was detected in 14 (24.1%) of the adenocarcinoma patients, KRAS mutation was detected in 12 (20.6%) patients. BRAF mutation was observed in 1 patient with adenocarcinoma (1.7%). KRAS mutation was observed in only 1 of the SCCs (3.3%). KRAS mutation was observed in 1 of the LCNECs (12.5%). EGFR mutation in adenocarcinoma cases was found to be significantly associated with female gender and nonsmoking status. There was no correlation between EGFR mutation and age, stage, tumor size, lymph node metastasis, distant metastasis and differentiation grade. No correlation was found between KRAS mutation and other factors. The BRAF mutation could not be assessed for association because the number of cases monitored was low. The microarray method we used in our study provided the scanning of the cases in terms of 50 different mutations commonly identified for the EGFR gene, single chip 24 different mutations for KRAS and BRAF gene in a total of 96 cases with NSCLC (Non Squamous Cell Lung Cancer) in three different subtypes at the same time and in a short time. We think our study will be useful in the development of treatment protocols and patient selection.

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Clinicopathological and prognostic features of surgically resected pathological stage I lung adenocarcinoma harboring epidermal growth factor receptor and K‐ras mutation

Cited by 10 publications

References 47 publications

Significance of the epidermal growth factor receptor mutation status and differences among molecular subgroups in surgically resected lung microinvasive adenocarcinoma

Significance of the epidermal growth factor receptor mutation status and differences among molecular subgroups in surgically resected lung microinvasive adenocarcinoma

Prognostic value of <em>EGFR</em> and <em>KRAS</em> in resected non-small cell lung cancer: a systematic review and meta-analysis

Determination of Epidermal Growth Factor Receptor (EGFR), KRAS and BRAF Mutation in Non Small Cell Lung Cancers Using Biofilm Chip Based Microarray Technology

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