The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival

Veale, D; Kerr, Naseem; Gibson, G. Edward; Kelly, Patrick J.; Harris, Adrian L.

doi:10.1038/bjc.1993.306

Cited by 202 publications

(114 citation statements)

References 20 publications

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“…whereas still others indicated that patients with EGFR-positive tumours may survive longer than patients without EGFR expression (Dazzi et al. 1989: Veale et al. 1993.…”

Section: Discussionmentioning

confidence: 99%

Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections

Pfeiffer

Clausen²,

Andersen³

et al. 1996

Br J Cancer

128

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Summary The prognostic role of the epidermal growth factor receptor (EGFR) and the related receptor p185HER-2 in lung cancer is as yet undefined. We investigated the immunohistochemical expression of EGFR (monoclonal antibody RI; Amersham) and pl85HER-2 (polyclonal antibody A485; Dako) in cryosections. A total of 186 unselected and systemically untreated patients with non-small-cell lung cancer (NSCLC) diagnosed and treated at Odense University Hospital, Denmark, were included. Median follow-up period was 66 months.EGFR and pl85HER-2 was highly expressed in 55% and 26% of cases respectively. Expression of EGFR was independent of pl85HER-2 expression. The expression of EGFR was higher in squamous cell carcinomas whereas the level of pl85HER-2 staining was higher in adenocarcinomas. Expression of either or both receptors was not correlated with age, histological grading, stage and prognosis. We conclude that immunohistochemical detection of these growth factor receptors failed to demonstrate a prognostic significance in patients operated on for NSCLC.

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“…whereas still others indicated that patients with EGFR-positive tumours may survive longer than patients without EGFR expression (Dazzi et al. 1989: Veale et al. 1993.…”

Section: Discussionmentioning

confidence: 99%

Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections

Pfeiffer

Clausen²,

Andersen³

et al. 1996

Br J Cancer

128

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“…Nicholson et al, 10 after reviewing the literature from 1985 to 2000 regarding EGFR and cancer types association, indicated that this marker was rarely related to other clinical and prognostic markers in NSCLC. However other studies had reported a relationship between EGFR expression and patient survival, 28 as well as a relationship between this expression and tumor pathogenesis progression. 29 In our cohort, there was no statistical correlation between diffuse membranous expression of EGFR and patient survival (P40.05).…”

Section: Study Of Altered E-cad and Egfr Expressions G Deeb Et Almentioning

confidence: 96%

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

et al. 2004

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E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important cell adhesion and signaling pathway mediators. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 130 resectable lung cancers (stages I-IIIA) were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into three blocks using a Beecher system. Immunohistochemistry was performed using an avidinbiotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in 410% of tumor cells was considered as a positive expression of E-cad and EGFR. Markers expression and coexpression were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 118, 126, and 115 cases that were fully assessable for E-cad, EGFR, and both markers, respectively. For E-cad, 65 cases (55%) were positive ( þ ), 53 (45%) were negative (À); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were ( þ ), and 83 (66%) were (À). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR( þ ) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P ¼ 0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(À)/EGFR( þ ) phenotype had poorer survival than those with E-cad( þ )/EGFR(À) (P ¼ 0.026). Our study suggests that lung AdC and SCC may be stratified based on expression of E-cad and EGFR with the E-cad(À)/EGFR( þ ) expression having a worse disease outcome. Moreover, the cytoplasmic expression of E-cad may represent an altered localization of this protein in association with tumorigenicity.

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“…9,10 However, the checkered history of EGFR IHC may represent a challenge to broad acceptance of these tools. Initially, measurement of EGFR was performed using radioligand binding assays, 11 which were difficult to conduct and poorly reproducible. These assays were replaced by IHC as the standard method for assessment of EGFR.…”

mentioning

confidence: 99%

Standardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer

Dimou

Agarwal

Anagnostou

et al. 2011

The American Journal of Pathology

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Challenges in measurement of epidermal growth factor receptor (EGFR) protein expression have led to conflicting data on its prognostic value and discontinuation of its use for prediction of response. Herein is described a quantitative standardized assay for EGFR and its use in a series of retrospective cohorts of patients with nonsmall cell lung cancer (NSCLC). The AQUA technology of quantitative immunofluorescence was used in conjunction with Western blot analysis to calculate the absolute concentration of EGFR in two independent NSCLC cohorts (170 from Yale New Haven Hospital and 335 from Sotiria and Patras Hospitals in Greece). EGFR and mutated EGFR were measured using D38B1 antibody and two mutation-specific antibodies. All patients positive or borderline for mutation-specific antibody were genotyped. A threshold for reproducible detection of EGFR was defined as 0.85 ng/ g total protein. EGFR expression demonstrated no prognostic value in either cohort. The mutation rate was 1.79% in the Yale cohort, and 1.52% in the Sotiria/Patras cohort, with no antibody detection-based false-positive cases. No mutations were detected for EGFR concentrations <1.46 ng/ g total protein. In summary, accurate measurement of EGFR still shows no prognostic value in NSCLC. In these two population-based cohorts, the antibody-based EGFR mutation rate was lower than has been frequently reported.

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The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival

Abstract: Summary Increased expression of epidermal growth factor receptor (EGFr)

Cited by 202 publications

References 20 publications

Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections

Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

Standardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer

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