Expression of microtubule-associated protein tau by gastrointestinal stromal tumors

The purpose of this work was to study the expression in gastrointestinal st romal tumors (GISTs) of various antigens, including the protein tau associa ted with enteric neuronal differentiation; to compare their expression with that of c-kit. known to be associated with interstitial cell of Cajal diff erentiation; and to correlate their expression with the observation of ultr astructural features of gastrointestinal autonomic nerve tumors. Twenty-six GISTs of the stomach and 16 GISTs of the small bowel were included in the study group. Thirty-five tumors served as controls. Tissue sections were im munostained with vimentin, CD34, desmin, specific smooth muscle actin, S100 protein, neuron-specific enolase, PGP9.5, neurofilament, bcl-2 oncoprotein , synaptophysin, chromogranin A, e-kit, and tau. Twenty-one of these tumors were also analyzed ultrastructurally. Of the 42 GISTs, 28 were predominant ly spindled, 7 were predominantly epithelioid, and 7 were a mixture of epit helioid and spindle cells. Ten primary GISTs were classified as benign, 9 a s borderline, and 23 as malignant. Metastatic dissemination was present at primary surgery in 1 case and eventually developed in 6 patients. Six disea se-related deaths were counted. In normal submucous and myenteric plexuses of stomach and small bowel, ganglion cell bodies and nerve fibers strongly expressed tau. Twenty (76.9%) GISTs of the stomach and 12 (75%) of the smal l bowel expressed tau. Tau often showed intense, diffuse staining patterns in both spindled and epithelioid tumors. Ten (100%) of the 10 benign GISTs, 7 (77.8%) of the borderline GISTs, and 15 (65.2%) of the 23 frankly malign ant GISTs expressed tau. Thirty-six GISTs expressed at least 2 different ne uronal markers. A coexpression of the neuronal markers and c-kit was observ ed in 90% of GISTs. The expression of tau was observed in 12 of the 15 GIST s with dense core granules, considered as the definitive finding for a diag nosis of gastrointestinal autonomic nerve tumors. Ten of these also express ed c-kit; 9 were malignant. Tau also immunostained other intra-abdominal tu mors, including neuroendocrine carcinomas, paragangliomas and desmoplastic round cell tumors. This immunohistochemical study shows that GISTs are spec ific tumors of the digestive tract and are nearly always characterized by s imultaneous neuronal and interstitial cell of Cajal differentiation. Althou gh the loss of tau expression is observed only in borderline and malignant tumors, its prognostic value is not clear cut. HUM PATHOL 32:1166-1173. Cop yright (C) 2001 by W.B. Saunders Company.