Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (<i>EGFR</i>) Mutations with the Classical Mutation Pattern

Wu, Shang‐Gin; Chang, Yih‐Leong; Hsu, Ya‐Chieh; Wu, Jo‐Hsuan; Yang, Chih-Hsin; Yu, Chong‐Jen; Tsai, Meng‐Feng; Shih, Jin‐Yuan; Yang, Pan‐Chyr

doi:10.1634/theoncologist.2008-0093

Cited by 70 publications

(79 citation statements)

References 54 publications

(45 reference statements)

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“…Recently, it was found that EGFR mutation was a sensitive marker of NSCLC to EGFR TKI drugs, while KRAS mutation was a resistant one [22,23]. Considering the incidence of gene mutations including EGFR and KRAS in NSCLC varied regionally and racially, we detected EGFR and KRAS mutations in 157 NSCLC patients from mainland China, and found that the mutation frequencies of EGFR and KRAS were both similar to reports from other East Asia areas, such as Taiwan China, Japan and Korea [19,[24][25][26][27][28]. Comparing to western countries, the mutation frequency of EGFR was higher, while that of KRAS was lower in the East Asia areas [20,29,30].…”

Section: Discussionmentioning

confidence: 57%

“…However, it is still unclear if the two type mutations in EGFR have different clinicopathological characteristics and clinical significance. It was noticed that patients with EGFR mutation in exon 19 had higher sensitive rates to TKI drugs and increased survival rates after treatment with TKI drugs in contrast to those with exon 21 mutations [11,[13][14][15][16][17][18], while some research groups didn't think so [19]. Shigematsu et al from Japan even thought patients with EGFR mutations of exon 21 exhibited an increase in survival if they had not received any form of chemotherapy including TKI drugs when compared to those with mutations of exon 19 [2].…”

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confidence: 99%

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The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China

Zhang²,

Liu³

et al. 2011

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Mutations of epithelial growth factor receptor (EGFR) in exon 19 and 21 are both believed to be associated with carcinogenesis, sensitivity to tyrosine kinase drugs and with the prognosis of non-small cell lung cancers (NSCLCs). However, their exact clinical significance remains disputable. We detected the mutations of 157 NSCLCs from mainland China with high resolution melting analysis and identified exon mutations with DNA sequencing. Of the 157 cases examined, 57 displayed EGFR mutations which included 22 in exon 19 and 35 in exon 21. Current research has shown that EGFR mutations are more commonly associated with the female population and East Asians, with additional significance being adenocarcinomas. Our current findings are supporting this sugestion. We analysed the clinicalpathological characteristics of mutations in exon 19 and 21 separately, which showed that the mutation frequency of NSCLCs in exon 21, but not in exon 19, were significantly higher in females. Comparatively, mutation frequencies in exon 19 were significantly higher in the stage I and II than in the stage III abnd IV, while tumors with lymph node metastasis and the stage III and IV demonstrated significantly higher mutation frequencies in exon 21. Additionally, exon mutations in the left and right lung showed significant differences: with exon 19 mutations being more frequent in the tumors of left lung, and exon 21 mutuations showing a higher incidence in right lung tumors. This suggests that, in mainland China, NSCLCs with EGFR mutations in exon 19 could have a less malignant character than those with mutations in exon 21. It's the first report that EGFR mutations in exon 19 and exon 21 in NSCLC patients may relate to the tumor sites, but further research is still required.

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Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 99%

The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China

Zhang²,

Liu³

et al. 2011

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“…EGFR overexpression is also associated with poor prognosis. 33,63 Solid pattern has more ERCC1 expression than acinar and this aspect is very important because ERCC1 repairs DNA and confers resistance to some drugs.…”

Section: Solid Patternmentioning

confidence: 99%

“…25---31 EGFR and HER2 play a central role in tumorigenesis. 32,33 Targeting those receptors provides a unique approach for treating EGFR/HER2 expressing cancers. 34,35 The most common alteration of HER2 is overexpression/amplification; mutations are less frequent.…”

Section: Introductionmentioning

confidence: 99%

“…34,35 The most common alteration of HER2 is overexpression/amplification; mutations are less frequent. 33,35,36 The activated receptors trigger Ras-Raf-MEK (mitogen-activated and extracellular signal regulated kinase), ERK1 and ERK2 (extracellular-signal regulated kinase 1 and 2) pathways leading to cell growth, mTOR (mammalian target of rapamycin) pathway leading to protein synthesis, and PI3K-AKT (phosphatidylnositol-2 kinase Akt) pathway sustaining cell survival. 36 The objectives of this work were to validate a small differentiation IHC panel, evaluate protein expression of different genes according to different adenocarcinoma patterns, and correlate this expression with cell pathways of progression and drug resistance, in order to understand bronchial-pulmonary adenocarcinoma carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

Sousa

Bastos

Silva

et al. 2015

Revista Portuguesa de Pneumologia (English Edition)

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Lung cancer is one of the most common cancers in the world with a high mortality rate. We analyzed 45 surgical samples of the adenocarcinoma, 13 with lymph node metastasis. APC, BCL2, chromogranin A, CK 5/6/18 (LP34), CK20, CK7, cyclin D1, EGFR, ERCC1, HER2, Ki67, LRP, MRP, P53, RB and TTF1 expressions were evaluated by immunohistochemistry (IHC).Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma.Acinar, micropapillary and BA/lepidic adenocarcinoma patterns were the most similar patterns and papillary was the most different pattern followed by solid pattern, according to expression of these markers. Different adenocarcinoma patterns are engaged with different molecular pathways for carcinogenesis, based on the differences of expression. Acinar, BA/lepidic and micropapillary showed higher TTF1 expression (type TRU), and papillary and solid patterns revealed less TTF1 expression, exhibiting a non-TRU/bronchial phenotype. Solid pattern revealed lower HER2 and higher EGFR and ERCC1 (this compared to papillary) expression; papillary higher HER2 and lower ERCC1 expressions; micropapillary higher RB expression; and acinar lower ERCC1 and higher EGFR expressions. Ciclin D1 seems to have more importance in acinar and BA/lepidic patterns than in micropapillary. ERCC1 protein expression in micropapillary, solid and BA/lepidic patterns may indicate DNA repair activation. Inhibition of apoptosis could be explained by BCL2 overexpression, present in all adenocarcinoma patterns. MRP-1 and LRP were overexpressed in all patterns, which may have implications for drug resistance.Further studies are needed to interpret these data regarding to therapy response in advanced staged bronchial-pulmonary carcinomas.

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Mechanisms of Resistance to Epidermal Growth Factor Receptor (EGFR) in Non‐Small Cell Lung Cancer

Massarelli

2014

Lung Cancer

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Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (EGFR) Mutations with the Classical Mutation Pattern

Cited by 70 publications

References 54 publications

The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China

The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

Mechanisms of Resistance to Epidermal Growth Factor Receptor (EGFR) in Non‐Small Cell Lung Cancer

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