Coordinated upregulation of COX-2 and NF-kappaB is a steady feature of laryngeal carcinogenesis.
OBJECTIVE
Laryngeal cancer is the endpoint of a multistage process involving hyperplastic and dysplastic lesions, not adequately defined in their molecular aspect. Our objective was to evaluate the expression of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) and the chief transcription factor nuclear factor-kappaB (NF-kappaB) in laryngeal carcinomas and their precursors, as well as to explore any association between the two molecules.


METHODS
We performed paraffin section immunohistochemistry for COX-2 and the p65 subunit of NF-kappaB, in tissues from 129 patients with tumors or premalignancies. p65 cytoplasmic and nuclear immunostaining were listed individually.


RESULTS
COX-2 was positively correlated with histopathological grading from normal mucosa to carcinomas (Spearman's coefficient r(s) = 0.286, p < 0.001). No association was revealed between COX-2 expression and tumor grade. p65 immunoreactivity, both of cytoplasmic and nuclear origin, increased along the carcinogenesis course, manifesting highest expression in invasive cancer (r(s) = 0.419, p < 0.001 and r(s) = 0.241, p < 0.001, respectively). Again, tumor grade had no influence on expression. COX-2 and p65 cytoplasmic, but no nuclear, expression showed a positive correlation (r(s) = 0.352, p < 0.001).


CONCLUSIONS
This study demonstrates that lesional advance in the larynx towards cancer is marked by ongoing upregulation of COX-2 and NF-kappaB. Synchronism between individual expressions may denote a regulatory role of the latter in COX-2 transactivation.
Kourelis
Konstantinos
K
Department of Anatomy, Medical School of Patras, Patras, Greece. ccourel@upatras.gr
Sotiropoulou-Bonikou
Georgia
G
Vandoros
Gerasimos
G
Repanti
Maria
M
Varakis
Ioannis
I
Goumas
Panagiotis
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000378:metabolism*; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics*
D008565:Membrane Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human