Expression levels of the nerve growth factor receptors TrkA and p75 in effusions and solid tumors of serous ovarian carcinoma patients

Purpose: The purpose of this study was to analyze the expression of the hig h- and low-affinity nerve growth factor (NGF) receptors TrkA and p75 in eff usions and in primary and metastatic tumors of serous ovarian carcinoma pat ients, as well as to evaluate their association with clinicopathological pa rameters and disease outcome. Experimental Design: Sections from 77 malignant effusions and 78 primary an d metastatic lesions were evaluated for protein expression of TrkA and p75 using immunohistochemistry (IHC). Expression of the phosphorylated form of TrkA (p-TrkA) was evaluated in 75 effusions using IHC. TrkA and p75 mRNA ex pression was studied in 44 effusions using reverse transcription-PCR (RT-PC R). Results: TrkA protein membrane expression was detected in carcinoma cells i n 30 of 77 (39%) effusions and 64 of 78 (82%) solid tumors. The decrease in TrkA expression in effusions approached, but did not reach, statistical si gnificance when only corresponding lesions were analyzed (P = 0.06 in the c omparison of effusions and primary tumors, P = 0.09 for effusions and metas tases). Conversely, p75 protein membrane expression was more common in effu sions, which was detected in 16 of 77 (21%) effusions as compared with 6 of 78 (8%) solid tumors (P > 0.05 in analysis of corresponding lesions). Expr ession of p-TrkA in carcinoma cells was limited to 5 of 75 effusions. Inter estingly, 11 of 16 p75-positive effusions were also immunoreactive for the antibody against TrkA (P = 0.001), suggesting NGF activation using two sign aling pathways. TrkA and p75 protein expression in tumor cells was similar in pleural and peritoneal effusions (P > 0.05). Using reverse transcription -PCR, TrkA mRNA was detected in 2 of 45 effusions, whereas p75 mRNA was pre sent in 3 of 45 specimens. TrkA and p75 showed no association with tumor gr ade, Federation Internationale des Gynaecologistes et Obstetristes stage, c hemotherapy status, the extent of residual disease, or survival (P > 0.05). Conclusions: TrkA and p75 are both expressed in advanced-stage ovarian carc inoma, but whereas p75 expression is elevated in effusions, TrkA shows an o pposite trend. The different expression of NGF receptors in effusions may r elate to the different microenvironment and growth factor availability in b ody cavities, as also supported by the infrequent activation of TrkA in eff usions. The similar expression of TrkA and p75 in carcinoma cells in pleura l and peritoneal effusions provides further evidence for our hypothesis tha t there are few, if any, phenotypic differences between ovarian carcinoma c ells at these two sites. TrkA and p75 expression in effusions does not appe ar to be a predictor of disease outcome in advanced-stage serous ovarian ca rcinoma.