The objective of this study was to compare the expression of the
nerve growth factor (
NGF) receptors TrkA and p75 in ovarian borderline
tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I
carcinomas and advanced-stage (FIGO stage III-IV)
carcinomas, and to assess a possible association between
NGF receptor expression and
mitogen-activated protein kinase (MAPK) activation in borderline
tumors and FIGO stage I
carcinomas. Sections from 119 borderline
tumors, 57 FIGO stage I invasive ovarian
carcinomas, and 56 advanced-stage
carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I
carcinomas and borderline
tumors using
phospho-specific antibodies against the extracellular-regulated
kinase (p-ERK), the high osmolarity
glycerol response
kinase (p-p38), and the
c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage
carcinomas compared with both borderline and stage I
carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I
carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian
carcinomas (P < .001).
NGF receptor expression showed no association with MAPK activation in borderline and stage I
carcinomas. In conclusion, expression of biologically active p-
TrkA receptor at the cell membrane is up-regulated along
tumor progression in ovarian
carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian
carcinoma.
NGF receptors probably signal via MAPK-independent pathways in ovarian
carcinoma.