Epidermal growth factor receptor (EGFR) status in different stages of resected non-small cell lung cancer (NSCLC): Implications for treatment with EGFR-targeted monoclonal antibodies

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20015-20015
Author(s):  
R. Berardi ◽  
M. Scartozzi ◽  
M. Squadroni ◽  
A. Santinelli ◽  
A. Brunelli ◽  
...  

20015 Background: Aim of our study was to verify potential changes in EGFR status in different stages of resected NSCLC. This was done in order to find out whether assessing the EGFR status could be considered an effective tool for planning therapy with EGFR-targeted monoclonal antibodies in different setting of patients. Methods: From January 1996 through December 2001, 439 patients underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche. EGFR expression was evaluated with an immunohistochemical technique on five micron-thick tissue sections obtained from specimens fixed in 10% (v/v) neutral buffered formalin and paraffin embedded.EGFR expression was detected as membranous and/or cytoplasmic brown staining of neoplastic cells with various intensity. Positivity for EGFR expression was defined as any membrane staining above background level. Both the primary and metastatic neoplasm were considered positive when ≥ 1% of the tumour cells had membranous staining. Results: Table 1 summarizes patients’ characteristics. Samples from 423 patients were available for EGFR analysis. EGFR immunohistochemical expression was found positive as follows: 15.8% in stage IIIB, 12.2% in IIIA, 2.3% in IIB, 5.3% in IIA, 4.8% in IB and 5% in IA. At multivariate analysis, EGFR status resulted indicator of prognosis both when considering all the patients and in the groups of patients with different stages of disease. Conclusions: Globally our findings seem to confirm the role of EGFR as a prognostic indicator in NSCLC. Furthermore the observation that EGFR is more frequently overexpressed in the advanced stages may suggest that EGFR-targeted treatment strategies could be more appropriated in this subgroup of patients. [Table: see text] No significant financial relationships to disclose.

Author(s):  
RODRIGO VIEIRA GOMES ◽  
MICHELE ÂNGELA RODRIGUES ◽  
JOÃO BERNARDO SANCIO ROCHA RODRIGUES ◽  
PAULA TEIXEIRA VIDIGAL ◽  
KARINE ARAÚJO DAMASCENO ◽  
...  

ABSTRACT Objective: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. Methods: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. Results: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. Conclusion: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.


2004 ◽  
Vol 22 (23) ◽  
pp. 4772-4778 ◽  
Author(s):  
Mario Scartozzi ◽  
Italo Bearzi ◽  
Rossana Berardi ◽  
Alessandra Mandolesi ◽  
Guidalberto Fabris ◽  
...  

Purpose We hypothesized that the detection of epidermal growth factor receptor (EGFR) expression performed in primary tumors for treatment with EGFR-targeted monoclonal antibodies could not always correlate with EGFR status in metastatic sites, thus making cancer cells in these sites resistant to therapy. The aim of our study was to correlate EGFR expression on primary tumors and related metastases in order to find out whether assessing EGFR status on primary cancer is to be considered an effective tool for planning treatment with EGFR-targeted antibodies. Patients and Methods We retrospectively evaluated EGFR immunohistochemistry from primary tumors and related metastatic sites in 99 colorectal cancer patients. The site of primary tumor was colon in 77 patients (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84 patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in five patients (5%). EGFR status was defined as positive if the percentage of malignant cells stained was ≥ 1%. Results EGFR status was positive in 53 primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the corresponding metastatic site was found negative, whereas it was found positive in seven metastases (15%) from EGFR-negative primary cancers. The difference between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR-negative to EGFR-positive) was statistically significant (P = .036). Conclusion Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).


Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.


2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.


2021 ◽  
Vol 22 (4) ◽  
pp. 1902 ◽  
Author(s):  
Yi-Shu Huang ◽  
Wei-Chuan Hsu ◽  
Chien-Hong Lin ◽  
Sheng-Nan Lo ◽  
Chu-Nian Cheng ◽  
...  

Epidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, 188Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of 188Re. Western blotting, MALDI-TOF, column size exclusion and flow cytometry were used to confirm the conjugation and bio-activity of 188Re-liposome-Fcy-hEGF. Cell lines with EGFR expression were subjected to treat with 188Re-liposome-Fcy-hEGF/5-FC in the presence of 5-FC. The 188Re-liposome-Fcy-hEGF/5-FC revealed a better cytotoxic effect for cancer cells than the treatment of liposome-Fcy-hEGF/5-FC or 188Re-liposome-Fcy-hEGF alone. The therapeutics has radio- and chemo-toxicity simultaneously and specifically target to EGFR-expression tumor cells, thereby achieving synergistic anticancer activity.


2015 ◽  
Vol 34 (6) ◽  
pp. 418-422 ◽  
Author(s):  
Tomohiro Osaki ◽  
Cai-Xia Wang ◽  
Taro Tachibana ◽  
Masayuki Azuma ◽  
Masaya Kitamura ◽  
...  

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