Protein microarrays for the detection of biomarkers in head and neck squamous cell carcinomas

Weber, Anette; Hengge, Ulrich R.; Stricker, Ingo; Tischoff, Iris; Markwart, Annett; Anhalt, Kathrin; Dietz, Andreas; Wittekind, Christian; Tannapfel, Andrea

doi:10.1016/j.humpath.2006.07.012

Cited by 55 publications

(45 citation statements)

References 32 publications

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“…However, it is well known that the development of HNSCC is an evolutionary process and is characterized by multistep carcinogenic processes in which activation of oncogenes and inactivation of tumor suppressor genes, including tumor protein 53 (TP53), epidermal growth factor receptor (EGFR), cyclin D1 (CCND1), and cyclin-dependent kinase inhibitor 2A (CDKN2A), are caused by genetic alterations and epigenetic modifications. [2][3][4][5] Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2), a highly conserved histone methyltransferase that methylates lysine-27 of histone H3 (H3-K27).…”

Section: Introductionmentioning

confidence: 99%

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Cao

Feng

Cui

et al. 2011

Cancer

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BACKGROUND:The authors previously observed that enhancer of zeste homolog 2 (EZH2) overexpression was associated significantly with the development of oral cancer. In the current study, they investigated whether EZH2 can function as a prognostic predictor for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Expression levels of EZH2 in HNSCC cells were detected using reverse transcriptase-polymerase chain reaction (PCR) and Western blot analyses. In addition, the effects of EZH2 ablation on the proliferation and invasion of HNSCC cells were investigated through small interfering RNA (siRNA)-mediated knockdown. Real-time PCR and immunohistochemistry were used to evaluate EZH2 and cyclin D1 expression in 46 HNSCC samples, and the expression levels also were re-evaluated in 124 independent samples by immunohistochemistry. RESULTS: EZH2 expression was elevated remarkably in HNSCC specimens and cell lines. Upon EZH2 silencing, the proliferation and invasion of HNSCC cells were remarkably suppressed. EZH2 expression frequently was correlated with cyclin D1 expression (P ¼ .034) and tumor differentiation (P ¼ .020). In addition, both EZH2 messenger RNA levels and EZH2 protein levels were strongly associated with signs of histologic severity (P ¼ .012 and P ¼ .032, respectively). Univariate analysis revealed that high EZH2 expression was associated with worse overall survival (P ¼ .001) and disease-free survival (P ¼ .002). The combined expression of EZH2 and cyclin D1 had superior prognostic ability for patients with HNSCC than the expression of either marker alone. In multivariate analysis, EZH2 expression was identified as an independent predictor of overall and disease-free survival. CONCLUSIONS: The current results indicated that EZH2 is an independent prognostic indicator for patients with HNSCC. In addition, an analysis of the combined expression of EZH2 and cyclin D1 can serve as a more powerful prognostic predictor for patients with HNSCC. Cancer 2012;118:2858-71.

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Section: Introductionmentioning

confidence: 99%

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Cao

Feng

Cui

et al. 2011

Cancer

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“…However, immunoreactivity for active MMP-7 was present only in cancer tissue and was correlated with tumor size and tumor invasion of the adjacent skin and mandible, suggesting that MMP-7 is activated in tumor cells and is associated with aggressive tumor behavior in buccal cancer. Weber et al 18 found that MMP-7 is mainly produced by tumor cells themselves and is associated with short survival times in head and neck cancer. de Vicente et al 22 also demonstrated that MMP-7 expression is significantly correlated with lymph node metastasis in oral cavity cancers.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17] According to a recent protein microarray study, MMP-7 was significantly upregulated in head and neck squamous cell carcinoma tissues. 18 However, the contribution of active MMP-7 vs MMP-7 in the progression of oral cancer has not been determined. [19][20][21][22][23] In the present study, we used tissue microarray together with immunohistochemistry and western blotting to analyze the expression of active MMP-7 in buccal squamous cell carcinoma and in normal tissues from the same patients and correlated these findings with clinicopathological features of buccal squamous cell carcinoma.…”

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confidence: 99%

Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma

Chuang

Huang

et al. 2008

Modern Pathology

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Protein microarrays have shown that matrix metalloproteinase-7 is upregulated in head and neck squamous cell carcinomas, but its role in local tissue invasion is still uncertain. We investigated the expression of active matrix metalloproteinase-7, using tissue microarray, immunohistochemistry, and western blotting, in oral tissues from 24 patients with buccal squamous cell carcinoma, and correlated the findings with clinicopathological features. Normal buccal tissue samples from the same patients, obtained at sites at least 1 cm from tumor tissue, served as normal controls. Total matrix metalloproteinase-7 was detected on western blots in 9 of 15 (60%) tumor tissue samples and in 2 of 15 (13%) normal mucosal samples; this difference was significant (P ¼ 0.008). Moreover, the active matrix metalloproteinase-7 was expressed only in eight of the nine (89%) tumor samples that expressed matrix metalloproteinase-7, and in none of the normal tissue samples, regardless of the expression status of the pro-matrix metalloproteinase-7. Immunostaining of matrix metalloproteinase-7 was observed histologically in both tumor and nonneoplastic epithelium, but immunostaining of active matrix metalloproteinase-7 was present only in tumor nests. Expression of active matrix metalloproteinase-7 was associated with larger tumor size (P ¼ 0.022) and was significantly higher in buccal squamous cell carcinoma with adjacent skin or bone invasion (P ¼ 0.036). In conclusion, active matrix metalloproteinase-7 expression was associated with more aggressive buccal squamous cell carcinomas.

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“…These proteins allow the cell to cope with the stress that they are subjected to (De Maio 1999). Hsp70, so named after its molecular weight of 70 kDa, is upregulated in HNSCC and functions in a protective manner against the surrounding environment (Weber et al 2007). Inactivation of Hsp70 increased the amount of remaining DNA double strand breaks after exposure to radiation, which in turn lead to increased apoptosis.…”

Section: Heat Shock Protein 70 (Hsp70)mentioning

confidence: 99%

Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma

Jedliński¹

2014

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Head and neck squamous cell carcinoma (HNSCC) originates from the epithelial lining of the upper aerodigestive tract. It accounts for over 90 % of the malignancies found in the head and neck region. 600,000 new cases of HNSCC occur each year worldwide. Apart from causing painful lesions, HNSCC directly impacts the patient’s fundamental functions such as breathing and eating and also can disrupt the patient’s senses such as smell, taste, speech and even vision. Most cases of HNSCC require a combination of different treatments such as surgery, chemotherapy (primarily cisplatin based), and radiotherapy. Treatment decisions are largely based on the size of the tumor, the involvement of local lymph nodes, and distant spread. Treatment resistance and local recurrence are significant problems and to date no form of clinical treatment sensitivity prediction is available. A majority of HNSCC tumors overexpresses the epidermal growth factor receptor (EGFR). This receptor is involved in proliferation and DNA repair and is the target of a monoclonal antibody named cetuximab that selectively binds and inhibits EGFR. It is the only targeted therapy available to HNSCC patients and reserved for late stage patients in Sweden. Numerous investigators have searched for predictive markers and we hypothesized that since HNSCC is a very heterogeneous disease a single factor would not be able to predict the treatment outcome. In paper I we explore a panel of predictive factors using a point system, called the number of negative points (NNP), in which we could combine both proteins and genetic variations in an attempt to find a set of markers that could predict the intrinsic cisplatin sensitivity (ICS). The expression level of EGFR, Hsp70, Bax, Bcl-XL, survivin, and COX-2 was determined in 39 HNSCC cell lines. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearson’s correlation tests showed that EGFR was the only protein that alone correlated to ICS (r=0.388, P=0.015). The strongest correlation to ICS was found when combining SNPs in XRCC3 and XPD with the expression of EGFR, Hsp70, Bax, and Bcl-2 using the NNP system (r=0.614 P≤0.001). In paper II we assess the intrinsic radiosensitivity (IR), the ICS, and the intrinsic cetuximab sensitivity (ICmabS) as well as their combinations in 25 HNSCC cell lines established from HNSCC biopsies taken at the Department of Otorhinolaryngology and Head and Neck Surgery at Linköping University Hospital. Furthermore we investigate the EGFR status (consisting of EGFR gene copy number, EGFR mRNA, EGFR protein, pEGFR), pAkt and mRNA levels of the seven known EGFR ligands. No correlation was found between the different treatment sensitivities. Cetuximab treatment response was significantly correlated to epiregulin (EREG) mRNA expression (r=-0.408, P=0.043). Cetuximab resistant cell lines tended to have low levels of pEGFR (P=0.13) while resistant cell lines had a significantly lower expression of EGFR pro...

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Protein microarrays for the detection of biomarkers in head and neck squamous cell carcinomas

Cited by 55 publications

References 32 publications

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma

Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma

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