Immunohistochemical Analysis of Phosphotyrosine Signal Transducer and Activator of Transcription 3 and Epidermal Growth Factor Receptor Autocrine Signaling Pathways in Head and Neck Cancers and Metastatic Lymph Nodes

Seethala, Raja R.; Gooding, William E.; Handler, Phoebe N.; Collins, Bobby; Zhang, Qing; Siegfried, Jill M.; Grandis, Jennifer R.

doi:10.1158/1078-0432.ccr-07-1543

Cited by 44 publications

(40 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, a recent study questioned the predictive value of o-EGFR in HNSCC [19]. On the other hand, we detected p-EGFR in 14 patients, all of whom overexpressed EGFR protein.…”

Section: Discussioncontrasting

confidence: 53%

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

et al. 2009

View full text Add to dashboard Cite

The molecular status of the epidermal growth factor receptor (EGFR) has not been as well studied in head and neck squamous cell carcinoma (HNSCC) as in lung cancer. We examined the frequencies of EGFR mutations as well as the expression/phosphorylation status of the EGFR protein in HNSCC patients. Moreover, we tried to elucidate associations between EGFR molecular status and patient characteristics and disease-free survival. In this prospective cohort study, clinical data and samples were obtained from 82 consecutive patients who had not been treated with EGFR molecular targeting therapy. Fulllength EGFR was sequenced, and expression and phosphorylation of the EGFR protein were measured by Western blotting. Four novel mutations (E709K, V765G, Ins770G, and G1022S) and one mutation well-known in lung cancer (L858R) were identified in six HNSCC samples (7%), but we could not find any mutations in the extracellular domain of EGFR, such as EGFRvIII, in this study. E709K and Ins770G as well as L858R appear to be functional mutations based on the use of Ba/F3 cells. In terms of patient characteristics, the number of metastatic lymph nodes and node stage were associated with phosphorylation of EGFR. No patients with EGFR mutations relapsed during the study period. Excluding mutated cases, patients whose tumor samples showed phosphorylated EGFR relapsed significantly earlier than those without phosphorylated EGFR. This finding was still significant after adjusting for mutation and overexpression of EGFR protein using the Cox proportional hazard model. In conclusion, phosphorylated EGFR without mutations may be a marker of poor prognosis in patients with HNSCC. The Oncologist 2009;14:900 -908

show abstract

“…In addition, a recent study questioned the predictive value of o-EGFR in HNSCC [19]. On the other hand, we detected p-EGFR in 14 patients, all of whom overexpressed EGFR protein.…”

Section: Discussioncontrasting

confidence: 53%

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

et al. 2009

View full text Add to dashboard Cite

show abstract

“…As suggested previously [29,30], we constructed a measure that combined these two aspects of protein expression into a single semi-quantitative measure. We called this measure the staining score and defined it as the product of intensity and percentage of cells staining, with the average score used for cases with two tumor blocks.…”

Section: Variable Definitionsmentioning

confidence: 99%

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

Troy

Weissfeld

Youk

et al. 2013

Head and Neck Pathol

Self Cite

View full text Add to dashboard Cite

There is current interest in anti-angiogenesis therapies for head and neck squamous cell carcinomas (HNSCC), although the utility of these therapies in human papillomavirus (HPV) positive and HPV-negative HNSCC is unclear. Therefore, we explored heterogeneity in expression of a distal factor in angiogenesis (EGFR, the epidermal growth factor receptor), a proximal factor in angiogenesis (VEGF, the vascular endothelial growth factor) and a putative factor in angiogenesis (NOTCH1) in a HNSCC case series using immunohistochemistry in N = 67 cases (27 HPV-positive, 40 HPV-negative, by in situ hybridization). Box plots and the Wilcoxon rank sum or Kruskal-Wallis tests were used to compare staining scores (intensity 9 percent of cells staining) by HPV status and lifestyle factors. Associations between EGFR, VEGF, and NOTCH1 were assessed using box plots and Spearman correlation (q) in all cases, and stratified by HPV status.

show abstract

“…The immunostaining pattern was frequently heterogeneous, exhibiting various staining intensities within a single neoplasm. Since there are no guidelines for scoring the samples, in agreement with previous published studies (21,22) we calculated a score based on the stain intensity of tumor cells: 0/1 (no or incomplete membrane staining); 2 (weak/ moderate complete membrane staining); and 3 (strong and complete membrane staining). Moreover, we considered the individual percentage of positive cells in each sample.…”

Section: Immunohistochemistrymentioning

confidence: 78%

“…According to the DakoCytomation EGFR pharmDX kit for EGFR testing a positive IHC stain for EGFR is defined as ≥ 1% of tumor cells showing partial or circumferential membrane staining of any intensity (above background), but many authors suggest to consider the membrane intensity with a score (0,1,2,3) and the percentage of positive cells (21,22). We decided to consider these parameters separately and to investigate the possible associations between them.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor overexpression/amplification in adenocarcinomas arising in the gastrointestinal tract

Rossi

Villanacci

Danesino

et al. 2011

Rev. esp. enferm. dig.

View full text Add to dashboard Cite

Introduction: it has been suggested that EGFR might be valuable to select patients for immunotherapy for various types of cancers.Aims: we investigated: a) the gene/proteins alterations in gastrointestinal cancers using immunohistochemistry (IHC) (gene overexpression) and fluorescence in situ hybridisation (FISH) (gene amplification); and b) the associations between EGFR overexpression and amplification and chromosome 7 aneusomy (CEP7) in these cancers.Methods: 64 tumor specimens were evaluated by IHC and FISH: 17 adenocarcinoma arising in Barrett's esophagus, 21 stomach cancers, 17 colon cancers, and 9 liver metastasis of colon carcinoma. IHC for EGFR was scored at 4 levels of intensity of membrane staining. EGFR gene in FISH was considered as amplified or not and chromosome 7 (where EGFR is located) as polisomic or disomic. The ratio between EGFR gene and chromosome 7 was performed by FISH and classified the case as gene amplification when the ratio was > 2. Polisomy was identified when the copies of chromosome 7 were > 2 in more than 8% malignant cells.Results: no difference was found between EGFR gene amplification/protein overexpression according to cancer site. Concerning IHC, most cases were positive for EGFR intensity (84.4%), while only 50% of cases were positive considering a cut-off of 10%. EGFR FISH amplification was found in 4 cases only (6.2%) and FISH CEP7 aneusomy in 40.6%. A statistically significant association was found between EGFR protein positivity (IHC) in term of intensity and EGFR gene amplification by FISH (p = 0.003), and between the EGFR protein positivity (IHC) and chromosome 7 aneusomy (FISH) (p = 0.004).Conclusions: EGFR amplification assessed by FISH was found in only 4 cases (6.2%) while chromosome 7 aneusomy was identified in 26 (40.6%) cases. IHC proved that EGFR protein overexpression in gastrointestinal cancers is common but FISH assessment showed that EGFR gene amplification is rare. An association was observed between EGFR gene amplification and EGFR protein overexpression in a low number of cases (p = 0.003). A statistically significant association was found between EGFR protein overexpression and chromosome7 polisomy (p = 0.004).

show abstract

Immunohistochemical Analysis of Phosphotyrosine Signal Transducer and Activator of Transcription 3 and Epidermal Growth Factor Receptor Autocrine Signaling Pathways in Head and Neck Cancers and Metastatic Lymph Nodes

Cited by 44 publications

References 38 publications

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

Expression of EGFR, VEGF, and NOTCH1 Suggest Differences in Tumor Angiogenesis in HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma

Epidermal growth factor receptor overexpression/amplification in adenocarcinomas arising in the gastrointestinal tract

Contact Info

Product

Resources

About