Analysis of Surgical Margins With the Molecular Marker eIF4E: A Prognostic Factor in Patients With Head and Neck Cancer

Nathan, Cherie‐Ann O.; Franklin, Scott; Abreo, Fleurette; Nassar, Raja; Benedetti, Arrigo De; Glass, Jonathan

doi:10.1200/jco.1999.17.9.2909

Cited by 116 publications

(104 citation statements)

References 15 publications

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“…Molecular markers can be used to establish tumour free surgical margins and assist in the complete resection of the tumour (4). The molecular marker, p53, has been established to predict for recurrence in the surgical margins (5,6).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma

Singh

Jayaraj

Baxi

et al. 2015

Molecular and Clinical Oncology

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Abstract. Molecular markers can be used to identify residual cancer at the surgical margins of head and neck squamous cell carcinoma (HNSCC) and assist in evaluating the complete resection of the tumour. The purpose of the present study was to investigate the expression levels of prognostic molecular markers at the histological tumour free surgical margins. In the present clinical retrospective study, 24/48 patients were selected with negative surgical margins for further analysis with immunohistochemical staining. Contingency tables and Fisher's exact tests were used to investigate the association between the expression levels of p53 and eukaryotic translation imitation factor 4E (eIF4E) with the clinical outcomes for patients with HNSCC. The expression levels of p53 and eIF4E were 54.2 and 87.5%, respectively, in the surgical margins of patients with HNSCC. A total of 3/7 patients with recurrent cancer (42.8%) were identified with p53-positive margins, and 6 (85.7%) patients exhibited recurrence with eIF4e-positive margins. No statistically significant differences were identified for the recurrence risk between the overexpression of p53 and eIF4E in the surgical margins (P=0.88 and P=0.99, respectively). The eIF4E marker appears to be a more marked prognosticator compared with p53, as overexpression of eIF4E was identified in the margins of 6/7 patients with local recurrence.

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Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma

Singh

Jayaraj

Baxi

et al. 2015

Molecular and Clinical Oncology

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“…Molecular markers can be used to establish tumour free surgical margins and assist in complete resection of the tumour (Nathan et al, 1999). To establish the reliable molecular cancer markers, the marker should be specific for tumour cells that could differentiate normal and tumour cells (Roncella et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

An Australian Retrospective Study to Evaluate the Prognostic Role of p53 and eIF4E Cancer Markers in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC): Study Protocol

Singh¹,

Jayaraj²,

Baxi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Complete surgical resection of the primary tumour is a crucial predictive step for head and neck squamous cell carcinoma (HNSCC), because incomplete resection may lead to increase in the recurrence rate. Molecular cancer markers have been investigated as potential predictors of prognosis marker, to identify patients who are at high risk of local recurrence. This retrospective study aimed to determine the prognostic correlation between p53 and eIF4E expression and clinical characteristics, recurrence and overall survival. 1-74 months). The Kaplan-Meier method was used to generate recurrence and survival curves. This is a first retrospective study of Northern Territory patients, including Indigenous and non-Indigenous Australians. Molecular study of surgical margins could help to identify patients with and without clear margins after surgery and help in choice of the most appropriate adjuvant treatment for HNSCC patients.

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“…Signaling pathways upstream and downstream of MTOR appear dysregulated in greater than 90% of HNSCC (8) and we have shown overexpression of EIF4E in tumor-free surgical margins is an independent predictor of recurrence (9) and is activated by the AKT/ MTOR pathway (10). In earlier studies, as the degree of dysplasia increased, there was an increase in EIF4E overexpression in surgical margins of HNSCC patients (11). Hence, AKT/MTOR pathway activation in premalignant oral cavity lesions could provide an important intermediate endpoint in chemopreventive agent trials.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits Carcinogen and Nicotine-Induced Mammalian Target of Rapamycin Pathway Activation in Head and Neck Squamous Cell Carcinoma

Clark

McEachern

Shah

et al. 2010

Cancer Prevention Research

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Curcumin appears to be a safe, bioactive food compound that is a potential chemopreventive for patients at a high risk for head and neck squamous cell carcinoma (HNSCC). Identification and validation of intermediate endpoints is an important step in evaluating chemopreventive agents. AKT/ MTOR pathway biomarkers are intrinsic to the carcinogenic process as well as the mechanism of intervention with curcumin. Antiproliferative effects of curcumin were assayed in 9 HNSCC and a keratinocyte cell line. Nicotine, a genotoxic alkaloid involved in tobacco addiction, forms DNA adducts and has been implicated in upper aerodigestive tract cancer promotion. The antiproliferative effects of curcumin were associated with inhibition of the AKT/MTOR pathway in presence and absence of nicotine, which also induced this pathway. Curcumin was highly effective at suppressing growth of SCC40 xenografts and its activity is associated with modulation of MTOR's downstream target pS6. Curcumin at 15 mg significantly increased survival (286 AE 37 vs. 350 days) in the 4NQO carcinogenic model survival study. A major cause of lethal progression of HNSCC is local regional migration and invasion of malignant cells, and curcumin significantly inhibited cancer cell migration and invasion in vitro and in vivo where downregulation of pS6 was associated with a significant decrease in MMP-9. This is the first study to demonstrate that curcumin inhibits the adverse effects of nicotine by blocking nicotine-induced activation of the AKT/MTOR pathway in HNSCC, which retards cell migration. These studies indicate that inhibiting the AKT/MTOR pathway with curcumin may be useful as an oral chemopreventive agent. Cancer Prev Res; 3(12); 1586-95. Ó2010 AACR.

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Analysis of Surgical Margins With the Molecular Marker eIF4E: A Prognostic Factor in Patients With Head and Neck Cancer

Abstract: In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.

Cited by 116 publications

References 15 publications

Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma

Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma

An Australian Retrospective Study to Evaluate the Prognostic Role of p53 and eIF4E Cancer Markers in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC): Study Protocol

Curcumin Inhibits Carcinogen and Nicotine-Induced Mammalian Target of Rapamycin Pathway Activation in Head and Neck Squamous Cell Carcinoma

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