title: Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma.
abstract: 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.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Montebello N-0310 Oslo, University of Oslo, Oslo, Norway. bend@ulrik.uio.no
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.forename: Björn
authors.initials: B
authors.lastname: Risberg
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Bilal
authors.initials: B
authors.lastname: Sert
authors.forename: Carlos
authors.initials: C
authors.lastname: Bedrossian
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology*; D010996:Pleural Effusion / Q000235:genetics* / Q000473:pathology*; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology*; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis*; D020917:Receptor, trkA / Q000096:biosynthesis*
chemical_list: D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA