Prognostic significance of cyclooxygenase-2 in laryngeal squamous cell carcinoma.
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
FO
Institute of Histology, Università Cattolica del S. Cuore, Roma, Italy. ranelletti@em.unicatt.it
Almadori
G
G
Rocca
B
B
Ferrandina
G
G
Ciabattoni
G
G
Habib
A
A
Galli
J
J
Maggiano
N
N
Gessi
M
M
Lauriola
L
L
D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000201:enzymology*; D002454:Cell Differentiation; D002460:Cell Line; D051546:Cyclooxygenase 2; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D015603:Keratinocytes / Q000201:enzymology; D007700:Kinetics; D007822:Laryngeal Neoplasms / Q000175:diagnosis* / Q000201:enzymology*; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011485:Protein Binding; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors