Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study

Silva, Sabrina D.; Agostini, Michelle; Nishimoto, Inês Nobuko; Coletta, Ricardo D.; Alves, Fábio Abreu; Lopes, Márcio Ajudarte; Kowalski, Luiz Paulo; Graner, Edgard

doi:10.1016/j.oraloncology.2004.01.004

Cited by 75 publications

(125 citation statements)

References 33 publications

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“…Loss of BRCA2 correlates with a significant decrease in survival time, and certain chromosomal deletions (i.e., 10q and 14q) were found to be associated with poor prognosis (33)(34)(35). Increased gene expression [i.e., NBS1, FGFR, Ki-67, HER2, matrix metalloproteinase 2 (MMP2) and MMP9, and cyclin D1] has been shown to indicate the aggressiveness of the disease (36)(37)(38)(39)(40)(41), and elevated alpha B-crystallin expression has been found to be a more sensitive marker for HNSCC recurrence than the combination of plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (42). However, there is still not a DNA methylation marker for poor prognosis (12).…”

Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Activity of CCAAT/Enhancer Binding Protein α Is Epigenetically Down-regulated in Head and Neck Squamous Cell Carcinoma

Bennett¹,

Hackanson

Smith

et al. 2007

Cancer Research

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Tumor suppressor CCAAT enhancer binding protein a (C/EBPa) is a transcription factor involved in cell cycle control and cellular differentiation. In a recent study, microarray expression profiling on head and neck squamous cell carcinoma (HNSCC) samples identified significant C/EBPa down-regulation, correlating with poor prognosis. However, the mechanisms of C/EBPa down-regulation remained elusive. C/EBPa has been previously found to provide an antiproliferative role in lung cancer, and our laboratory showed that its down-regulation involves epigenetic mechanisms. This prompted us to investigate the involvement of epigenetics in down-regulating C/EBPa in HNSCC. Here, we show that C/EBPa is down-regulated in HNSCC by loss of heterozygosity and DNA methylation, but not by gene mutation. We found a consistently methylated upstream regulatory region (À1,399 bp to À1,253 bp in relation to the transcription start site) in 68% of the HNSCC tumor samples, and DNA demethylation using 5-aza-2 ¶-deoxycytidine treatment was able to significantly restore C/EBPa mRNA expression in the HNSCC cell lines we tested. In addition, C/EBPa overexpression in a HNSCC cell line (SCC22B) revealed its ability to provide tumor suppressor activity in HNSCC in vitro and in vivo. In conclusion, we showed for the first time not only that C/EBPa has tumor suppressor activity in HNSCC, but also that it is down-regulated by DNA promoter methylation. [Cancer Res 2007;67(10):4657-64]

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Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Activity of CCAAT/Enhancer Binding Protein α Is Epigenetically Down-regulated in Head and Neck Squamous Cell Carcinoma

Bennett¹,

Hackanson

Smith

et al. 2007

Cancer Research

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“…Having observed a marked reduction in tumor size and growth rate, we assayed for the presence of the Ki-67 molecular marker, and following immunohistochemical analysis, the number of positive cells in all treatment groups was quantified at 400Â magnification. This proliferation marker is expressed in the G 1 -S-G 2 phases of the cell cycle and is commonly expressed in tumors and associated with progression or poor prognosis (36,37). p12 therapy caused a decrease in the fraction of cells expressing the proliferation marker Ki-67 (Fig.…”

Section: Increased Expression Of P12mentioning

confidence: 99%

p12CDK2-AP1 Gene Therapy Strategy Inhibits Tumor Growth in an In vivo Mouse Model of Head and Neck Cancer

Figueiredo¹,

Kim²,

Marcus

et al. 2005

Clinical Cancer Research

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Purpose: To test the potential of p12 CDK2-AP1 (p12), a cell cycle regulator and cyclin-dependent kinase-2-associating protein commonly down-regulated in head and neck squamous cell carcinoma (f70%), as a gene therapy in inhibiting head and neck squamous cell carcinoma growth in vivo. Experimental Design: We addressed the effect of p12 expression on tumor growth by using a well-established squamous cell carcinoma VII/SF floor of mouth xenograft mouse model. The effect of therapy on tumor growth was determined for: (a) no treatment, (b) PBS, (c) vehicle (1,2-dioleoyloxy-3-trimethylammonium propane:cholesterol liposomes / 5 % dextrose), (d) empty vector controls, and (e) p12-encoding vector experimental groups. Results: p12 gene therapy significantly induced antitumor effects as compared with controls, including (a) size and weight of p12-treated tumors decreased by 51% to 72% compared with all controls (P < 0.02), (b) tumor growth rate post-therapy was inhibited by 55 % to 64% compared with empty vector controls (P < 0.0001), and (c) p12 expression was higher in p12-treated than controls (P < 0.002) by two-tailed t test analyses. Mechanistically, p12 treatment affected cell turnover kinetics as assessed by apoptotic and cell proliferation indices. p12 therapy significantly increased terminal nucleotidyl transferase^mediated nick end labeling (P < 0.05) and morphology-based apoptotic indices (P < 0.05) as well as significantly decreased Ki-67 cell proliferation indices (P < 0.001) compared with controls, resulting in a net cell turnover reduction in p12-treated tumors. Conclusions: We show that this novel therapeutic modality can significantly induce antitumor responses in vivo. These results support a role for p12 as a novel tumor growth suppressor gene therapy and suggest that optimization and/or combination with current therapies may hold considerable promise in preparation for clinical trials.

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“…The c-erbB-2 proto-oncogene (HER/NEU/neu) encodes a 185 transmembrane protein product of tyrosine kinase family, with an extensive homology to the epidermal growth factor receptor, which has been mapped to the 21 region of chromosome 17 (Albuquerque et al, 2003) and can be activated by hetero oligomerization with the other members of the ErbB family (Silvaa et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

HER2/neu Expression in Head and Neck Squamous Cell Carcinoma Patients is not Significantly Elevated

Sardari¹,

Pardis²,

Andisheh-Tadbir³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: HER2/neu, a member of EGFR family, is over expressed in some tumors .The purpose of this study was to determine the salivary level and tissue expression of HER2/neu in patients with head and neck squamous cell carcinoma (HNSCC) and any correlation with clinicopathologic parameters. Methods: An enzymelinked immunosorbent assay (ELISA) was used to evaluate the salivary level and immunohistochemistry (IHC) to assess tissue expression of HER2/neu in 28 patients with HNSCC and 25 healthy controls. Results: The salivary levels of HER2/neu in HNSCC patients was not significantly higher than in the healthy controls (p>0.005). There was no apparent correlation in salivary HER2/neu level with clinicopathological features such as age, sex, grade, tumor size and nodal status. All HNSCC specimens were positive (membranous or/and cytoplasmic) for HER2/ neu, except one sample. Only one HNSCC specimen was stained in cytoplasm purely. All control specimens were membranous and cytoplasmic positive for HER2/neu. There was a significant difference between cytoplasmic staining in case and control groups (p-value<0.05). Conclusion: In our cases, no overexpression of HER2/neu was observed. Thus, our findings suggested that the use of Her-2 as a salivary marker of HNSCC cannot be recommended.

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Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study

Cited by 75 publications

References 33 publications

Tumor Suppressor Activity of CCAAT/Enhancer Binding Protein α Is Epigenetically Down-regulated in Head and Neck Squamous Cell Carcinoma

Tumor Suppressor Activity of CCAAT/Enhancer Binding Protein α Is Epigenetically Down-regulated in Head and Neck Squamous Cell Carcinoma

p12CDK2-AP1 Gene Therapy Strategy Inhibits Tumor Growth in an In vivo Mouse Model of Head and Neck Cancer

HER2/neu Expression in Head and Neck Squamous Cell Carcinoma Patients is not Significantly Elevated

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