Abstract
Epidermal growth factor receptor (EGFR) overexpression is an unfavorable prognostic marker in laryngeal squamous cell carcinoma (SCC). EGFR stimulates cyclooxygenase-2 (COX-2) expression in normal human keratinocytes and squamous carcinoma cells. Based on these observations a prognostic role of COX-2 expression in laryngeal SCC can be hypothesized. Consequently, COX-2 expression was studied in laryngeal SCC (median follow-up = 47 months; range: 2-87 months) by quantitative immunohistochemistry (n = 61) and EGFR by binding assay (n = 51). Well-differentiated regions of laryngeal SCC revealed strong COX-2 immunostaining, whereas histologically normal areas neighboring tumor as well as poorly-differentiated tumors were negative. Immunohistochemical results were confirmed by Western blot analyses. Cox's regression analysis showed that the combination of low levels of COX-2 integrated density and high levels of EGFR covariates provided strong prediction, at 5-year follow-up, of both poor overall survival (chi(2) = 12.905; p = 0.0016) and relapse-free survival (chi(2) = 9.209; p = 0.01). In vitro studies on CO-K3 cell line, obtained from an EGFR positive, COX-2 negative poorly-differentiated laryngeal SCC, revealed that EGF stimulation failed to induce COX-2 expression and PGE2 production suggesting a change in EGFR signaling pathway. These findings indicate that COX-2 is overexpressed in less aggressive, low grade laryngeal SCC, whereas its expression is lost when tumors progress to a more malignant phenotype.
Lingua originale | English |
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pagine (da-a) | 343-349 |
Numero di pagine | 7 |
Rivista | International Journal of Cancer |
Volume | 95 |
Stato di pubblicazione | Pubblicato - 2001 |
Keywords
- Aged
- Blotting, Western
- Carcinoma, Squamous Cell
- Cell Differentiation
- Cell Line
- Cyclooxygenase 2
- Disease-Free Survival
- Dose-Response Relationship, Drug
- Follow-Up Studies
- Humans
- Immunohistochemistry
- Isoenzymes
- Keratinocytes
- Kinetics
- Laryngeal Neoplasms
- Membrane Proteins
- Middle Aged
- Multivariate Analysis
- Phenotype
- Prognosis
- Prostaglandin-Endoperoxide Synthases
- Protein Binding
- Receptor, Epidermal Growth Factor
- Signal Transduction
- Time Factors
- Tumor Cells, Cultured
- Up-Regulation