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.

Ranelletti, F. O., Almadori, G., Rocca, B., Ferrandina, M. G., Ciabattoni, G., Habib, A., Galli, J., Maggiano, N., Gessi, M., Lauriola, L., Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma, <<INTERNATIONAL JOURNAL OF CANCER>>, 2001; 95 (6): 343-349 [http://hdl.handle.net/10807/25308]

Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma

Ranelletti, Franco Oreste;Almadori, Giovanni;Rocca, Bianca;Ferrandina, Maria Gabriella;
2001

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.
2001
Inglese
Ranelletti, F. O., Almadori, G., Rocca, B., Ferrandina, M. G., Ciabattoni, G., Habib, A., Galli, J., Maggiano, N., Gessi, M., Lauriola, L., Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma, <<INTERNATIONAL JOURNAL OF CANCER>>, 2001; 95 (6): 343-349 [http://hdl.handle.net/10807/25308]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/25308
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