TY - JOUR
T1 - Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma
AU - Davidson, Ben
AU - Reich, Reuven
AU - Lazarovici, Philip
AU - Flørenes, Vivi Ann
AU - Risberg, Björn
AU - Nielsen, Søren
AU - Sert, Bilal
AU - Bedrossian, Carlos
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
KW - Effusions
KW - Malignant mesothelioma
KW - Neurotrophins
KW - p75
KW - Tyrosine kinase receptors
UR - http://www.scopus.com/inward/record.url?scp=1842634536&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2003.11.014
DO - 10.1016/j.lungcan.2003.11.014
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C2 - 15084380
AN - SCOPUS:1842634536
SN - 0169-5002
VL - 44
SP - 159
EP - 165
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -