ABSTRACT: The purpose of this study was to examine whether a relationship exists between HIF-1alpha expression and the pro-apoptotic protein p53 in supraglottic laryngeal squamous cell carcinomas (SCCs), which could provide information concerning patient prognosis.
The study population was composed of 106 previously untreated men with SCC of the supraglottic larynx. All the patients underwent surgical resection of the tumor and bilateral neck dissection. Immunohistochemical analysis of HIF-1alpha and p53 protein expression was performed in relation with clinicopathological parameters and prognosis.
HIF-1alpha nuclear expression was detected in 71% of primary carcinomas and 55% of the paired lymph node metastases. There was a significant positive correlation between HIF-1alpha and T-classification but no associations were observed with other clinicopathological variables and with prognosis. There was no correlation between the expression of HIF-1alpha and p53. HIF-1alpha overexpression in combination with p53 immunostaining was not associated with disease recurrence or survival.
The data suggest that HIF-1alpha expression does not have a prognostic value in surgically treated supraglottic laryngeal SCC, and that immunohistochemical determination of p53 does not allow improving the clinical significance of HIF-1alpha.
Journal of Surgical Oncology 03/2009; 99(6):373-8. · 2.10 Impact Factor
ABSTRACT: Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies.
British Journal of Cancer 05/2008; 98(7):1274-84. · 5.04 Impact Factor
ABSTRACT: To develop a reliable animal model able to reproduce the behavior of head and neck squamous cell carcinomas (HNSCC). This model should facilitate our understanding of the molecular mechanisms of tumorigenicity and progression of these tumors, as well as the evaluation of novel therapies.
20 nude mice nu/nu were injected intraorally and submucosally with a cell line derived from a human squamous cell carcinoma of the glottis.
90% of the mice developed locally agressive squamous cell carcinomas, invading the surrounding muscle fibers and into loose connective tissue structures. All the tumors showed perineural growth. Four (22%) of the 18 mice showed bone destruction, and 22% vascular invasion. Tumor cells invaded lymphatic vessels in all the specimens, and 100% of the mice developed regional lymph node metastases. None of the animals developed haematogenous metastases.
We present a metastasing model of HNSCC that resembles its human counterpart in many aspects.
Acta Otorrinolaringológica Española 04/2005; 56(3):89-95.