Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma.

The objective of the present report was to study the expression of the low affinity nerve growth factor (NGF) receptor p75 and of the activated high-affinity NGF receptor TrkA in malignant mesothelioma (MM). In addition, to analyze whether expression of these receptors is site-related (pleural versus peritoneal MM, solid lesions versus effusions). Sections from 81 MM (57 biopsies, 24 effusions) were analyzed. Sixty-one mesotheliomas were of pleural origin, while the remaining 20 were peritoneal. Effusion specimens consisted of 6 peritoneal and 18 pleural effusions, while biopsies consisted of 14 peritoneal and 43 pleural lesions. Specimens were immunohistochemically stained using antibodies against p75 and phospho-TrkA (p-TrkA). Six effusions were additionally analyzed for p-TrkA expression using immunoblotting (IB). p-TrkA membrane expression (66/81 specimens; 81%) was by far more frequent than that of p75 (26/81 specimens; 32%). In addition, p-TrkA expression was significantly higher in peritoneal MM compared to their pleural counterparts (20/20 versus 46/61 positive tumors; P = 0.014). p-TrkA membrane expression was marginally higher in effusions (P = 0.058), while the opposite was true for p75 membrane expression (P = 0.008) and p-TrkA cytoplasmic expression (P = 0.003). In conclusion, our results document for the first time frequent expression of p-TrkA and lower expression of p75 in MM, in agreement with the biological aggressiveness of this tumor. The enhanced expression of p-TrkA in peritoneal MM, tumors that appear in younger patients, and in effusions as compared to solid tumors, suggest that p-TrkA plays a significant role in the biology of this disease and may aid in defining tumor progression in this setting.