Expression of tyrosine hydroxylase (TH) in human tumors: a tissue microarray study evaluating 18,666 tumors from 150 different tumor entities

TH immunohistochemistry (IHC) has been proposed as a sensitive and specific tool for the distinction of pheochromocytomas or paragangliomas from epithelial neuroendocrine neoplasms and tumors. However, little is known about the prevalence of TH expression in other tumor entities. To comprehensively evaluate TH expression in normal and tumor tissues, a tissue microarray containing 18,666 samples from 150 different tumor types and subtypes and 608 samples of 76 different normal tissue types were analyzed by IHC. TH immunostaining in tumors was always cytoplasmic. It was detectable in 158 (1%) of the 15,630 analyzable tumors, including 23 (0.1%) with weak, 28 (0.2%) with moderate, and 107 (0.7%) with strong positivity Overall, 14 of 150 tumor categories showed detectable TH expression and only 5 tumor categories included at least one case with strong TH positivity. TH staining was most frequent in pheochromocytomas (100%, including 74.0% with strong positivity), ganglioneuroma (25.0%; including 16.7% with strong positivity), paragangliomas "probably sympathetic" (50.0%; including 43.8% with strong positivity), and paragangliomas "probably parasympathetic" (13.6%; of which all showed strong positivity). Other tumor types showing TH positivity less commonly and at a lower level included medullary thyroid carcinoma (5.9%), squamous cell carcinomas of several organs of origin (up to 4.5%), neuroendocrine neoplasms from several organs (up to 4.3%) and colorectal adenocarcinoma (0.2%). In "non-neural crest" derived tumors, TH staining was often limited to few interspersed cells. In conclusion, a strong positive TH immunostaining is highly specific for pheochromocytomas, ganglioneuroma, and paragangliomas although sensitivity is < 30% for paragangliomas.