EGFR, HER2, and HER3 Expression in Laryngeal Primary Tumors and Corresponding Metastases

Wei, Qichun; Sheng, Liming; Shui, Yongjie; Hu, Qiong; Nordgren, Hans; Carlsson, Jörgen

doi:10.1245/s10434-007-9771-3

Cited by 57 publications

(59 citation statements)

References 36 publications

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“…Sections, 4-µm thick, were cut and deparaffinized in xylene and hydrated through graded concentrations of ethanol to distilled water (14)(15)(16)(17). The samples were then stained with hematoxylin and eosin for routine clinical analysis and, for this specific research project, with immunohistochemical receptor staining, as described below.…”

Section: Patients and Samplesmentioning

confidence: 99%

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Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors

et al. 2012

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Abstract. The epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extracellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab, or antibodies labeled with therapeutically useful radionuclides or toxins. This is especially the case when the tumor cells are resistant to chemotherapy and tyrosine kinase inhibitors. Studies concerning the expression of these receptors in prostate cancer vary in the literature, possibly due to differences in patient inclusion, sample preparations and scoring criteria. In our study, EGFR, HER2 and HER3 expression was analyzed in prostate cancer samples from primary tumors and corresponding lymph node metastases from 12 patients. The expression of HER2 and EGFR was scored from immunohistochemical preparations and the HercepTest criteria (0, 1+, 2+ or 3+), while HER3 expression was scored as no, weak or strong staining. There were 5 EGFR-positive (2+ or 3+) primary tumors and 6 EGFR-positive lymph node metastases, and there was EGFR upregulation in one metastasis. Only 4 of the 12 patients had marked HER2 expression (2+ or 3+) in their primary tumors and there was one downregulation and 5 cases of upregulation in the metastases. Thus, a total of 8 out of 12 analyzed metastases were HER2-positive. Of the 12 primary tumors, 9 expressed HER3 while only 2 of the lymph node metastases expressed recognizable HER3 staining, so 7 metastases appeared to have downregulated HER3 expression.In one of the primary tumors there was positive co-expression of EGFR and HER2, while this co-expression was observed in 4 of the metastases. Thus, there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. The results are encouraging for studies involving more patients. Possible strategies for EGFR-and HER2-targeted therapy are briefly discussed in the present study, especially with regard to the expression and co-expression of EGFR and HER2 in metastases.

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Section: Patients and Samplesmentioning

confidence: 99%

“…EGFR was assessed by immunohistochemistry using a streptavidin-biotin complex technique as previously described (14,15,17). After deparaffinization of the sections, endogenous peroxidase was blocked in 0.3% H 2 O 2 in PBS for 20 min.…”

Section: Patients and Samplesmentioning

confidence: 99%

Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors

et al. 2012

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“…Wei et al reported EGFR overexpression in 87.5% of laryngeal primary tumors, of which 82.5% had lymph node metastases (17). CerbB2 overexpression occurred in only 10.5% of the cases while lymph node metastasis occurred in only 1% of the cases.…”

Section: Discussionmentioning

confidence: 98%

The expression of EGFR, cerbB2, p16, and p53 and their relationship with conventional parameters in squamous cell carcinoma of the larynx*

Simsek¹,

Han²,

Önal³

et al. 2014

Turk J Med Sci

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IntroductionMany ions can be found in water as dissolved, absorbed/ adsorbed, or suspended matter, and the content of the ions determines whether the water is polluted. Some of the components in water can be recognized as exceeding safe limits or toxic. Wastes in open and partially enclosed quarries left behind after mining operations contain metals or toxic trace elements, and drainage waters that are rich in elements can mix into the surface water. These elements can be carried by acid water downstream and run-off to the sea, as either dissolved species or an integral part of suspended material, resulting in numerous environmental problems (Duruibe et al., 2007 and references therein).The oxidation of sulfide minerals, e.g., pyrite, chalcopyrite, sphalerite, and galena, exposed to atmospheric oxygen during or after mining operations produces acidic waters with high concentrations of dissolved iron, sulfate, and metals or semimetals, thus posing a health hazard to humans (Mrozek et al., 2006 and reference therein). Acid mine drainage (AMD) may cause environmental pollution by the dissolution and contamination of hazardous elements in aqueous systems.The investigation area is situated in a metallogenic area in the Black Sea region, NE Turkey (Figures 1 and 2). This area comprises approximately 400 Cu-Zn-Pb sulfide deposits of various sizes and types. The variable sizes of the VMS deposits are tectonically controlled in the Eastern Black Sea region and are hosted by hydrothermally altered peripheral zones in the Maastrichtian-Eocene volcanics.Although some of the mines were abandoned hundreds of years ago, the impact of AMD continues. Drainage from the ores and their host rocks, abandoned mines, and wastes have been polluted and regularly discharged into surface waters. The mixing of these waters into the ground and surface waters has resulted in serious problems or undesirable effects for all living things in the area. Due to the wet climate conditions and rainfall in the Black Sea region, streams flow throughout the year. The waters with low pH can leach some heavy metals, such as As, Cd, Pb, Sb, and Tl, and some toxic trace elements, such as Al, Cu, Fe, Se, and Zn, from the ores and host rocks. In the study area, the polluted rivers' and streams' surface waters have been used in agriculture and animal husbandry. Thus, the dissolved or suspended metals and

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“…The radiolabeling of the molecules seemed to not disturb the binding to any significant degree, as indicated by the competitive administration of non-labeled substances to the cultured cells. Immunohistochemical stainings for HER2 were performed as described in several of our previous reports on clinical tumor samples (36,37). The digital image analyses of the autoradiographs were performed using modified versions of previously described procedures and software (12,38).…”

Section: Discussionmentioning

confidence: 99%

“…Staining was enzymatically developed with 3, 3-diaminobenzidine-tetra hydrochloride [DAB, Dako Sweden AB. Such procedures have been described in more detail (36,37)]. …”

Section: Growth Of Spheroidsmentioning

confidence: 99%

Effects of affinity on binding of HER2-targeting Affibody molecules: Model experiments in breast cancer spheroids

Tran

2011

Int J Oncol

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Abstract. Binding of a targeting agent in tumor tissue is influenced by many factors such as molecular weight, charge and affinity of the targeting agent and vascularization of the tumor. In this study, we analyzed tumor cell binding of three HER2-specific and radiolabeled Affibody molecules with different affinities. The Affibody molecules had affinities in the range of 0.12-3.8 nM. Cellular binding was analyzed, after 2 h of incubation, in tumor spheroids composed of BT474 breast cancer cells, which highly express HER2. Binding was, due to the binding-site barrier, limited to the outer 15±5 µm rim of the spheroids, independent of affinity when the concentration of the substances was low. When the concentration was high, the binding site barrier was overcome and the binding occurred approximately 35±5 µm into the spheroids for the two high affinity substances and 50±5 µm for the low affinity substance. The lower affinity might allow for penetration into deeper regions due to less firm binding. We conclude that there is a binding site barrier within tumor spheroids which can be overcome by increased concentration of substance and modified by affinity.

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EGFR, HER2, and HER3 Expression in Laryngeal Primary Tumors and Corresponding Metastases

Cited by 57 publications

References 36 publications

Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors

Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors

The expression of EGFR, cerbB2, p16, and p53 and their relationship with conventional parameters in squamous cell carcinoma of the larynx*

Effects of affinity on binding of HER2-targeting Affibody molecules: Model experiments in breast cancer spheroids

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