The
Warthin tumor represents the second most frequent benign
tumor of the parotid gland and is characterized by the presence of oncocytes rich in structurally and functionally altered mitochondria. Next to its role in metabolism,
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is also implicated in cellular mitophagy. Immunohistochemistry was carried out on
Warthin tumor and normal control (parotid gland with striated ducts) tissues, using anti-GAPDH specific
antibodies followed by digital image analysis.
Laser capture microdissection was used to isolate the oncocytic
tumor cell and normal control striated duct compartments for
RNA extraction and qPCR.
Warthin tumor oncocytes exhibited a markedly spotted GAPDH staining pattern exhibiting cells with cytoplasmic and nuclear, only nuclear or none GAPDH staining. A significantly lower (p < 0.0001) total GAPDH signal was detected in
Warthin tumor oncocytes. Similarly, significantly lower (p < 0.005) GAPDH
mRNA levels were seen in oncocytes compared with normal ductal cells. To exclude the possibility of this GAPDH staining pattern being a general feature of oncocytic
neoplasms of different organs, we tested a cohort of
renal oncocytoma and oncocytic chromophobe
carcinoma; none showed this type of staining. The observed progressive GAPDH loss in
Warthin tumor oncocytes could be implicated in the pathogenesis of Warthin
tumors.