scholarly journals Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

2010 ◽  
Vol 29 (1) ◽  
Author(s):  
Giovanni Simone ◽  
Anita Mangia ◽  
Andrea Malfettone ◽  
Vincenza Rubini ◽  
Michele Siciliano ◽  
...  
Keyword(s):  
Copy Number ◽  
Lung Metastases ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Fine Needle ◽  
Egfr Gene ◽  
Fine Needle Aspirates

Prospective Study of Gefitinib in Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization–Positive/Phospho-Akt–Positive or Never Smoker Patients With Advanced Non–Small-Cell Lung Cancer: The ONCOBELL Trial

2007 ◽  
Vol 25 (16) ◽  
pp. 2248-2255 ◽  
Author(s):  
Federico Cappuzzo ◽  
Claudia Ligorio ◽  
Pasi A. Jänne ◽  
Luca Toschi ◽  
Elisa Rossi ◽  
...  
Keyword(s):  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Gene Copy ◽  
Fish Analysis ◽  
Small Cell Lung ◽  
Egfr Gene ◽  
Epidermal Growth

Purpose In non–small-cell lung cancer (NSCLC), clinical and biologic predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies, and there is urgent need to validate these results in prospective trials. The ONCOBELL trial is a prospective phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt. Patients and Methods EGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and presence of phospho-Akt was evaluated using immunohistochemistry. Additional tests included immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation analysis of EGFR, HER2, and K-ras. Results From November 2004 to February 2006, 183 patients were screened, and 42 patients were enrolled onto the trial. We observed one complete and 19 partial responses, for an overall response rate (RR) of 47.6% (95% CI, 32.5% to 62.7%). Median duration of response was 6.1 months, median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, and median survival time was not reached. EGFR FISH–positive patients, compared with negative patients, had higher RR (68.0% v 9.1%, respectively; P < .001), longer TTP (7.6 v 2.7 months, respectively; P = .02), and a trend for longer survival (median survival not reached v 7.4 months, respectively; P = .3). Therapy was well tolerated, and there were no drug-related deaths. Median follow-up time was too short for significance tests of differences in survival outcomes. Conclusion Gefitinib is active and well tolerated in patients with trial characteristics, and EGFR FISH analysis is an accurate predictor for such therapy.

scholarly journals Correlation between MET Gene Copy Number by Silver In Situ Hybridization and Protein Expression by Immunohistochemistry in Non-small Cell Lung Cancer

2012 ◽  
Vol 7 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Rafal Dziadziuszko ◽  
Murry W. Wynes ◽  
Shalini Singh ◽  
Bernadette Reyna Asuncion ◽  
James Ranger-Moore ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung

Exploratory analysis of EGFR FISH criteria in Japanese non-small cell lung cancer patients treated with gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7599-7599
Author(s):  
K. Kazuo ◽  
L. E. Morrison ◽  
H. Kimura ◽  
T. Sone ◽  
T. Araya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Control Fish ◽  
Small Cell Lung ◽  
Egfr Gene

7599 Background: In the phase III Iressa (gefitinib) Survival Evaluation in Lung cancer (ISEL) trial, high epidermal growth factor receptor (EGFR) gene copy number was a predictor of a gefitinib effect on survival in patients (pts) with refractory advanced non-small-cell lung cancer (NSCLC) (hazard ratio 0.61 vs 1.16 for high vs low copy number; p=0.045) [JCO 2006;24:5034–42]. Although EGFR mutation status may predict response to gefitinib in Japanese pts, there is insufficient data to clarify if high EGFR gene copy number assessed by fluorescence in situ hybridization (FISH) is predictive in these pts. This analysis investigated the applicability of both published Colorado FISH criteria (Colorado Univ) and new FISH criteria to Japanese NSCLC pts. Methods: 58 tumor specimens from gefitinib-treated Japanese pts were analyzed using Vysis LSI EGFR and CEP7 (chromosome 7 control) FISH probes. Specimens were classed as FISH+ or - using Colorado and exploratory (EGFR/cell; CEP7/cell; EGFR/CEP7; % of cells with various numbers of EGFR or CEP7 signals) criteria. Results: Of the 58 pts, 17 (29%) had an objective response (OR). Using Colorado criteria, OR was 50% in the 14 FISH+ pts vs 23% in the 44 FISH- pts (2-sided Fisher's exact test p=0.089). There was a trend for an association between FISH+ status and improved survival (log rank p=0.15). Defining FISH+ as specimens with =5% cells containing >5 EGFR signals, OR was significantly better among FISH+ pts vs FISH- pts (p=0.0030; 52% of the 23 FISH+ pts responding vs 14% of the 35 FISH- pts). A survival advantage was not indicated. Defining FISH+ as =74% of cells with EGFR or CEP7 loss (<2 signals) or gain (>2 signals), OR was significantly better among FISH+ pts vs FISH- pts (p=0.043; 45% of the 22 FISH+ pts responding vs 19% of the 36 FISH- pts). Association with survival had marginal significance (log rank p=0.061). Conclusions: These preliminary data have identified loss or gain of EGFR and CEP7 abnormality as promising biomarkers for response to gefitinib in Japanese NSCLC patients. Analysis of these markers for correlation with time to progression is ongoing. Investigation of these potential markers in other cohorts of patients is worthy of further evaluation. [Table: see text]

Comparison between epidermal growth factor receptor (EGFR) gene in primary non-small cell lung cancer (NSCLC) and in fine needle aspirates from metastatic sites

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21081-21081
Author(s):  
C. Bozzetti ◽  
M. Tiseo ◽  
C. Lagrasta ◽  
R. Nizzoli ◽  
F. Leonardi ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Metastatic Site ◽  
Fine Needle ◽  
Egfr Gene ◽  
Fine Needle Aspirates ◽  
Metastatic Sites

21081 Background: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently proposed to predict which non-small cell lung cancer patients (NSCLC) are expected to benefit from EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared to primary NSCLC. In all studies, FISH have been performed on histological material. The possibility to perform FISH analysis on cytological material obtained by fine-needle aspiration from superficial and deep metastases would allow to know the real EGFR status when the metastatic site is not accessible for biopsy. Methods: EGFR gene copy number was analyzed by FISH on fine-needle aspirates (FNAs) obtained from 18 patients with metastatic NSCLC (11 lymphnod, 2 liver, 1 abdomen, 2 skin, 2 pleural effusion) and results were compared with those obtained on corresponding paraffin histological sections from the primary tumor. Results: The feasibility of EGFR-FISH on cytology was 89%; 2/18 samples were not evaluable because of lack of hybridization. EGFR-FISH was positive (= 4 EGFR copy number; Cappuzzo F. et al, JNCI 2005) in 69% (11/16) of the metastases and in 38% (6/16) of the primary tumors. Five of the 16 cases were EGFR positive on both primary tumor and metastatic site and 4 were negative on both primary tumor and metastasis. Seven cases (44%) showed primary tumor vs. metastasis discordance: in 6 cases EGFR was positive in the metastatic site but not in the primary tumor, while in one sample EGFR was positive in the primary tumor but not in the metastasis. Conclusions: EGFR-FISH can be reliably assessed on FNAs obtained from NSCLC metastases. Possible changes in EGFR status during the metastatic progression as well as cancer heterogeneity may account for discrepancies observed between primary tumor and metastatic sites. These findings should be considered in future studies which will be design to better elucidate the predictive role of EGFR-FISH in NSCLC. No significant financial relationships to disclose.

Non-small cell lung cancer: Classical tumor markers versus EGFR gene copy number

2019 ◽  
Vol 493 ◽  
pp. S159-S160
Author(s):  
L. Valiña Amado ◽  
M. Enver Sumaya ◽  
A. Azkárate Martínez ◽  
E. Martínez Font ◽  
M.M. Parera Rosselló ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Markers ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Egfr Gene
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