In this article, detailed immunolocalization of the expression of receptor tyrosine kinase (Trk) in a wide range of normal and cancer nonneuronal tissues is described. Trk immunoreactivity is detected at various levels in all tissues examined, except for the heart and liver. The gastric parietal cells reveal strong TrkA and TrkC expression and all of the Trk immunoreactivities are expressed in the putative intestinal neuroendocrine cells. In the pancreas, TrkA and TrkC are detected in the subintralobular ducts, while TrkB is found specifically in the pancreatic beta cells. The lymph node and spleen exhibit TrkB in monocytes/macrophages. The adrenal cortex show selective TrkA with TrkC in the medulla. In the reproductive system, TrkA immunoreactivity is detected in the prostatic epithelial cells, TrkC in the ovarian theca and granulosa cells, TrkA and TrkC in the secretory-phase endometrium, and TrkA in the mammary ducts. The kidney reveal strong TrkA and TrkC in its tubules, but no Trk receptors are present in the glomeruli. In the skin, TrkA and TrkB/TrkC are expressed in the basal and granular layers of the epidermis, respectively. The expression patterns of TrkA in 337 nonneuronal invasive carcinomas of 15 different human tissues are also demonstrated iminunohistochemically. Overall, 133 (39%), 101(30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA immu noreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers are low. TrkA expression is detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, including the esophagus, breast, lung and uterus, but also in those from TrkA-negative cells of the thyroid, liver and ovary. Immunostaining for beta-NGF, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrates its immunoreactivity in stromalfibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine and autocrine regulation via stromal/tumoral NGF- tumoral TrkA interaction may be involved in growth of certain nonneuronal carcinomas.
Biomedical Reviews 1999; 10: 55-68.
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