Immunohistochemistry Profile Predicts EGFR Mutation Status in Lung Adenocarcinoma

2020 ◽  
Vol 28 (5) ◽  
pp. 502-506
Author(s):  
Wencheng Li ◽  
Angela G. Niehaus ◽  
Stacey S. O’Neill
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Mutation Status ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Napsin A ◽  
Therapeutic Decisions

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.

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

2014 ◽  
Vol 48 (2) ◽  
pp. 173-183 ◽  
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.

scholarly journals Relationship of TTF-1 and EGFR on Lung Adenocarcinoma at Dr. Saiful Anwar General Hospital Malang

2020 ◽  
Vol 31 (1) ◽  
pp. 43
Author(s):  
Andy Lumban gaol ◽  
Suryanti Dwi Pratiwi ◽  
Ngakan Putu Putra ◽  
Eviana Norahmawati ◽  
Harun Al Rasyid
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Exact Test ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Epidermal Growth ◽  
Relationship Of ◽  
The Relationship ◽  
Transcription Factor 1

<p>There is a correlation between mutation of Epidermal Growth Factor Receptor (EGFR) and lung adenocarcinoma. Unfortunately, examination for EGFR mutation is difficult because surgery must be conducted to obtain the best specimen. Thyroid Transcription Factor-1 (TTF-1) is a marker for lung adenocarcinoma. This observational study took place at Dr. Saiful Anwar Hospital from stored biological materials from 2013-2018. Samples were lung adenocarcinoma patients that undergo EGFR examination. Data then analyzed using Fischer's Exact Test to determine the relationship between EGFR and TTF-1. Specificity/sensitivity value is 0.75/0.90, p: 0.617, odds ratio 0.333 (0.032-3.515). However, Receiver Operating Characteristic (ROC) curve of TTF- 1 show AUC 0.614 (95CI, 0.35- 0.878). TTF-1 examination has a moderate strength in determining EGFR mutation on lung adenocarcinoma patients at Dr. Saiful Anwar Hospital.         </p>

scholarly journals Esophageal metastases from primary lung cancer: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Chang-Yong Wang ◽  
Gang Xu ◽  
Chuan Gao ◽  
Dong Wang
Keyword(s):  
Lung Cancer ◽  
Primary Lung Cancer ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Pathological Examination ◽  
Esophageal Metastasis ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Napsin A ◽  
Metastatic Sites

Abstract Background Primary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. There are no cases of esophageal metastases from lung cancer which refer to its particular treatment. Case presentation We report a case of esophageal metastases from lung cancer. The patient was a 55-year-old Han Chinese man who first attended our hospital due to dry cough and was diagnosed with late-stage lung cancer. Three months later, the patient complained of dysphagia. Endoscopic ultrasonography (EUS) and pathological examination of the biopsy specimen was performed to confirm the lesion was metastases from lung cancer. Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A were positive by immunohistochemistry examination. These results reconfirmed the diagnosis of esophageal metastases from lung cancer. Conclusions Esophageal metastasis from lung cancer is very rare. It may be alleviated with personalized chemotherapy. In addition, molecular targeted therapy for patients with epidermal growth factor receptor (EGFR) mutations may be reasonable.

scholarly journals Correlation of Thyroid Transcription Factor-1 Expression with EGFR Mutations in Non-Small-Cell Lung Cancer: A Meta-Analysis

Medicina ◽  
2019 ◽  
Vol 55 (2) ◽  
pp. 41
Author(s):  
Hyeong Su Kim ◽  
Jung Han Kim ◽  
Boram Han ◽  
Dae Ro Choi
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Objectives: This meta-analysis investigated the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) to clarify whether TTF-1 can be a potential surrogate marker for EGFR mutation status in advanced NSLCL. Methods: A systematic searching of databases, including PubMed, EMBASE, Cochrane Library, and Google Scholar, was performed to identify studies assessing the correlation of TTF-1 expression with EGFR mutations. From 17 studies, 9764 patients were included in the combined analysis of odds ratio (OR) for the correlation between TTF-1 expression and EGFR mutations. Results: Compared with NSCLCs showing negative TTF-1 expression, tumors harboring TTF-1 overexpression showed a significantly higher rate of EGFR mutations (OR = 5.19, 95% confidence interval: 3.60–7.47, p < 0.00001). This correlation was observed in both subgroups of East Asian (OR = 4.33, 95% CI: 3.46–5.41, p < 0.00001) and European patients (OR = 4.64, 95% CI: 1.41–15.28, p < 0.01). In addition, TTF-1 expression was significantly associated with EGFR mutations in exon 19 (OR = 4.63, 95% CI: 2.89–7.41, p < 0.00001) as well as exon 21 (OR = 3.16, 95% CI: 1.04–9.60, p = 0.04). Conclusions: This meta-analysis demonstrates a significant correlation between TTF-1 expression and EGFR mutations in patients with NSCLC. The status of TTF-1 expression may be a biomarker to guide anticancer treatment in patients with NSCLC and unknown EGFR mutation status.

Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

2021 ◽  
pp. 030089162110055
Author(s):  
Dashi Zhao ◽  
Jun Fan ◽  
Li Peng ◽  
Bo Huang ◽  
Yili Zhu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma ◽  
Sporadic Cases ◽  
Epidermal Growth ◽  
Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

scholarly journals MUC5AC enhances tumor heterogeneity in lung adenocarcinoma with mucin production and is associated with poor prognosis

2020 ◽  
Vol 50 (6) ◽  
pp. 701-711
Author(s):  
Yujie Dong ◽  
Lijuan Zhou ◽  
Dan Zhao ◽  
Kun Li ◽  
Zichen Liu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Egfr Mutations ◽  
Driver Mutations ◽  
Kras Mutations ◽  
Mucin Production ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Abstract Objective The clinicopathological significance of Mucin5AC (MUC5AC) in lung adenocarcinoma with mucin production is still unclear. This study aimed to explore MUC5AC expression in lung adenocarcinoma with mucin production and its correlation with histological subtypes, common driver mutations and its impact on prognosis. Methods MUC5AC and thyroid transcription factor 1 immunohistochemistry was performed on surgical samples from 90 patients with lung adenocarcinoma with mucin production. Common driver mutations including EGFR and KRAS mutations and ALK rearrangement were detected by established methods. Results MUC5AC was significantly associated with lymphovascular invasion (P = 0.023) and tumors with intra-cytoplasmic mucin (P &lt; 0.001). Moreover, MUC5AC was more significant in invasive mucinous adenocarcinoma (P &lt; 0.001), as well as in tumors with KRAS mutations (P = 0.005) and a lack of thyroid transcription factor 1 expression (P &lt; 0.001). Conversely, MUC5AC was less significantly detected in acinar predominant adenocarcinoma (P = 0.036) and tumors with EGFR mutations (P = 0.001). Notably, MUC5AC in non-pure mucinous subtype of lung adenocarcinoma with mucin production showed more aggressive behavior, distinct expression pattern and a lack of significant correlation with thyroid transcription factor 1 (P = 0.113) when compared with pure mucinous subtype. MUC5AC-positive tumors were significantly associated with a worse prognosis compared to MUC5AC-negative tumors (P &lt; 0.001). A multivariate survival analysis showed that MUC5AC was an independent prognosis factor for poor prognosis (P = 0.006). Conclusions The clinicopathological features of non-pure mucinous subtype of lung adenocarcinoma with mucin production were distinct and should be distinguished from pure mucinous subtype. MUC5AC was associated with poor prognosis and could be a potential therapeutic target for this distinct type of lung adenocarcinoma that has few effective treatments.

scholarly journals A Predictive Model of EGFR Mutation Status in Patients with Lung Adenocarcinoma Based on PET/CT Metabolic Indexes and Clinicopathological Variables

2020 ◽  
Author(s):  
Yanlong Yang ◽  
Shuchen Shi ◽  
Qianzhun Huang ◽  
Wenzhao Zhong ◽  
Juntao Lin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Growth Pattern ◽  
Egfr Mutation ◽  
Clinicopathological Characteristics ◽  
Metabolic Parameters ◽  
Smoking History ◽  
Egfr Mutations ◽  
Wild Type ◽  
Mutation Status ◽  
Pet Ct

Abstract PurposeThe purpose of this study was to create a mathematical model based on the metabolic parameters of PET/CT with clinicopathological characteristics to predict the EGFR mutation status of patients with lung adenocarcinoma.MethodsThis study retrospectively enrolled patients with lung adenocarcinoma who underwent surgical treatment at two centres in China between January 2012 and December 2015. PET/CT metabolic parameters and Classical EGFR mutation status detection by molecular pathology were performed before and after surgery, and we analysed the associations of EGFR mutation status with patient sex, age, smoking history, maximum primary lesion diameter, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), TNM stage and histopathological subtype of lung adenocarcinoma.ResultsA total of 310 patients were included, comprising 161 with EGFR mutations (51.9%) and 149 with wild-type EGFR (48.1%). EGFR mutations were more common in females, non-smokers, and those with stage IV disease, a low SUVmax, and ≤35 mm nodules, whereas wild-type EGFR was more common in males, smokers, and those with a solid growth pattern. Multivariate analysis suggested that liver SUVratio, smoking history, tumour size, TNM stage, and solid growth pattern can predict EGFR mutation status, and these factors were used to construct a mathematical model.ConclusionThe prediction model constructed in this study based on clinicopathological characteristics and PET/CT parameters might offer a basis by which to predict Classical EGFR status and provide a certain reference value for guiding the use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with lung adenocarcinoma.

scholarly journals Driver gene alterations in lung adenocarcinoma: Demographic features of 2544 Chinese cases

2020 ◽  
Vol 35 (4) ◽  
pp. 44-50
Author(s):  
Mingming Hu ◽  
Tongmei Zhang ◽  
Yuan Yang ◽  
Nanying Che ◽  
Jie Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Age Groups ◽  
Growth Factor Receptor ◽  
Distinct Group ◽  
Egfr Mutations ◽  
Driver Gene ◽  
Driver Genes ◽  
Anaplastic Lymphoma ◽  
Arms Pcr

Background: To understand the association between driver gene variations and age and gender in patients with lung adenocarcinoma, we investigated mutations of the three most important driver genes—epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) fusion genes and c-ros oncogene 1 (ROS1)—in this retrospective cohort study. Methods: Patients newly diagnosed with lung adenocarcinoma who received EGFR and ALK/ROS1 gene tests at our hospital from September 2014 to May 2019 were enrolled. EGFR mutations and ROS1 fusions were examined by ARMS-PCR and ALK fusions by Ventana-D5F3 IHC assay and ARMS-PCR. Results: Of 2544 eligible subjects, 2539 accomplished EGFR mutation tests. The prevalence of EGFR mutations was 62.1% in females, higher than that of 45.1% in males. In females, the EGFR mutation rate remained relatively stable at 60%–65% across the six age groups. Females showed an increased distribution of EGFR L858R and a decreased distribution of exon 19 deletion (19Del) by age. The incidence of ALK/ROS-1 rearrangements decreased significantly with age. Conclusions: EGFR 19Del mutation is more prevalent in younger males and females, while L858R mutation is prevalent in older females. Both ALK and ROS1 rearrangements are more common in younger lung adenocarcinoma. The young lung adenocarcinoma population is a distinct group rich in targetable genomic alterations, and more research is needed to understand the mechanism.

Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non–small cell lung cancer and brain metastases

2020 ◽  
Vol 133 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Cheng-Chia Lee ◽  
Sanford P. C. Hsu ◽  
Chung-Jung Lin ◽  
Hsiu-Mei Wu ◽  
Yu-Wei Chen ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Cox Regression ◽  
Gamma Knife Radiosurgery ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Tumor Control ◽  
Mutation Status ◽  
Epidermal Growth ◽  
Egfr Mutant

OBJECTIVEThe presence of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).METHODSThis study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.RESULTSThe tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).CONCLUSIONSThe current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

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