The impact of PRDX4 and the EGFR mutation status on cellular proliferation in lung adenocarcinoma

Significant advances in targeted therapy have been made in recent years for patients with lung adenocarcinoma. These targeted therapies have made molecular testing of paramount importance to drive therapeutic decisions. Material for testing is often limited, particularly in cytology specimens and small core biopsies. A reliable screening tool is invaluable in triaging limited tissue and selection for epidermal growth factor receptor ( EGFR) mutation testing. We hypothesized that the immunohistochemistry (IHC) profile of lung adenocarcinoma predicts EGFR mutation status. In this retrospective study, we evaluated the thyroid transcription factor-1 (TTF-1)/napsin A IHC profile and EGFR mutation status in 339 lung adenocarcinomas at our academic institution. In our cohort, we found that 92.3% of cases were positive for TTF-1 and/or napsin A by IHC with an EGFR positivity rate of 17.3%. Importantly, 7.7% of the cases were dual TTF-1/napsin A negative, and none of these cases contained EGFR mutations. This finding supports the use of TTF-1 and napsin A IHC to identify cases where EGFR mutation status will be negative, thus preserving limited tissue for other ancillary testing.

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Unique MicroRNA and mRNA Interactions in EGFR-Mutated Lung Adenocarcinoma

Journal of Clinical Medicine ◽

10.3390/jcm7110419 ◽

2018 ◽

Vol 7 (11) ◽

pp. 419 ◽

Cited By ~ 3

Author(s):

Sophia Subat ◽

Kentaro Inamura ◽

Hironori Ninomiya ◽

Hiroko Nagano ◽

Sakae Okumura ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Mrna Expression ◽

Regulatory Network ◽

Egfr Mutation ◽

Expression Profiles ◽

Integrative Analysis ◽

Future Research ◽

Mutation Status ◽

Egfr Mutated ◽

Insight Into

The EGFR gene was one of the first molecules to be selected for targeted gene therapy. EGFR-mutated lung adenocarcinoma, which is responsive to EGFR inhibitors, is characterized by a distinct oncogenic pathway in which unique microRNA (miRNA)–mRNA interactions have been observed. However, little information is available about the miRNA–mRNA regulatory network involved. Both miRNA and mRNA expression profiles were investigated using microarrays in 155 surgically resected specimens of lung adenocarcinoma with a known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis of the data was performed to identify the unique miRNA–mRNA regulatory network in EGFR-mutated lung adenocarcinoma. Expression profiling of miRNAs and mRNAs yielded characteristic miRNA/mRNA signatures (19 miRNAs/431 mRNAs) in EGFR-mutated lung adenocarcinoma. Five of the 19 miRNAs were previously listed as EGFR-mutation-specific miRNAs (i.e., miR-532-3p, miR-500a-3p, miR-224-5p, miR-502-3p, and miR-532-5p). An integrative analysis of miRNA and mRNA expression revealed a refined list of putative miRNA–mRNA interactions, of which 63 were potentially involved in EGFR-mutated tumors. Network structural analysis provided a comprehensive view of the complex miRNA–mRNA interactions in EGFR-mutated lung adenocarcinoma, including DUSP4 and MUC4 axes. Overall, this observational study provides insight into the unique miRNA–mRNA regulatory network present in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.

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Correlations Between the EGFR Mutation Status and Clinicopathological Features of Clinical Stage I Lung Adenocarcinoma

Medicine ◽

10.1097/md.0000000000001784 ◽

2015 ◽

Vol 94 (42) ◽

pp. e1784 ◽

Cited By ~ 8

Author(s):

Tetsuya Isaka ◽

Tomoyuki Yokose ◽

Hiroyuki Ito ◽

Masashi Nagata ◽

Hideyuki Furumoto ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Clinical Stage ◽

Clinicopathological Features ◽

Stage I ◽

Mutation Status

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Detection of EGFR Mutation Status in Lung Adenocarcinoma Specimens with Different Proportions of Tumor Cells Using Two Methods of Differential Sensitivity

Journal of Thoracic Oncology ◽

10.1097/jto.0b013e31823c4c1b ◽

2012 ◽

Vol 7 (2) ◽

pp. 355-364 ◽

Cited By ~ 53

Author(s):

Hye-Suk Han ◽

Sung-nam Lim ◽

Jin Young An ◽

Ki Man Lee ◽

Kang Hyeon Choe ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Tumor Cells ◽

Egfr Mutation ◽

Differential Sensitivity ◽

Mutation Status

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EGFR gene copy number alterations are not a useful screening tool for predicting EGFR mutation status in lung adenocarcinoma

Pathology ◽

10.1097/pat.0000000000000027 ◽

2014 ◽

Vol 46 (1) ◽

pp. 32-36

Author(s):

Prudence A. Russell ◽

Y.U. Yong ◽

D.O. Hongdo ◽

Timothy D. Clay ◽

Melissa M. Moore ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Copy Number ◽

Screening Tool ◽

Egfr Mutation ◽

Gene Copy Number ◽

Gene Copy ◽

Copy Number Alterations ◽

Mutation Status ◽

Egfr Gene

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Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival

Radiology and Oncology ◽

10.2478/raon-2014-0016 ◽

2014 ◽

Vol 48 (2) ◽

pp. 173-183 ◽

Cited By ~ 31

Author(s):

Karmen Stanic ◽

Matjaz Zwitter ◽

Nina Turnsek Hitij ◽

Izidor Kern ◽

Aleksander Sadikov ◽

...

Keyword(s):

Brain Metastases ◽

Lung Adenocarcinoma ◽

Cumulative Incidence ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Mutation Status ◽

Course Of Disease ◽

Epidermal Growth ◽

Egfr Mutant

AbstractBackground. The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methods. We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.Results. Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.Conclusions. Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

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