Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma
Article first published online: 14 AUG 2001
Copyright © 2001 Wiley-Liss, Inc.
International Journal of Cancer
Volume 95, Issue 6, pages 343–349, 20 November 2001
How to Cite
Ranelletti, F. O., Almadori, G., Rocca, B., Ferrandina, G., Ciabattoni, G., Habib, A., Galli, J., Maggiano, N., Gessi, M. and Lauriola, L. (2001), Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma. Int. J. Cancer, 95: 343–349. doi: 10.1002/1097-0215(20011120)95:6<343::AID-IJC1060>3.0.CO;2-D
- Issue published online: 17 AUG 2001
- Article first published online: 14 AUG 2001
- Manuscript Accepted: 4 JUN 2001
- Manuscript Revised: 28 MAY 2001
- Manuscript Received: 7 MAR 2001
- epidermal growth factor receptor;
- laryngeal squamous cell carcinoma;
- prognostic markers
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 (χ2 = 12.905; p = 0.0016) and relapse-free survival (χ2 = 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. © 2001 Wiley-Liss, Inc.