Expression of nicotinamide adenine dinucleotide phosphate oxidase flavoprotein DUOX genes and proteins in human papillary and follicular thyroid carcinomas

Duox2, and probably Duox1 are glycoflavoproteins involved in the thyroid H2 O2 generator functionally associated to thyroperoxidase (TPO). We investiga ted both DUOX1 and DUOX2 gene expressions using quantitative reverse transc ription-polymerase chain reaction (RT-PCR) in 47 thyroid carcinomas, includ ing 10 paired normal/tumoral tissues. In carcinomas, variations of DUOX1 an d DUOX2 mRNA levels were parallel, indicating that control mechanisms of bo th gene expressions operate in tumors as well as in normal thyroid tissues; DUOX1 expression was in the normal range in 20, was decreased up to 50-fol d in 8, and increased up to 7-fold in 19 samples. DUOX2 expression was in t he normal range in 15, was decreased up to 200-fold in 10, and increased up to 5-fold in 22 samples. In the 10 paired samples, variations of DUOX and TPO gene expressions were not correlated. We analyzed Duox1/2 protein expre ssion in 86 tumor samples using an antipeptide antiserum reacting with both Duox proteins. In normal tissue, Duox proteins are localized at the apical pole of thyrocytes, with 40% to 60% of thyrocytes being stained. In the 86 cancer tissues, immunostaining was absent in 19 samples, was low in 32, an d normal or even slightly increased in the other 35 samples. The expression of Duox proteins was related to tumor differentiation, being more frequent ly found in neoplastic tissues that were able to pick up radioiodine, and i n those with a detectable expression of sodium iodide symporter (NIS), pend rin and TPO.