A-kinase anchoring protein 3 messenger RNA expression correlates with poor prognosis in epithelial ovarian cancer.
OBJECTIVE
Cancer-testis (CT) antigens are expressed in tumors but not normal tissues except the testis and could be targets for vaccine therapy in epithelial ovarian cancer (EOC). A-kinase anchoring protein 3 (AKAP-3) is a novel member of the CT antigen family. The aim of this study was to examine the expression of AKAP-3 in EOC and correlate with clinico-pathologic characteristics.


METHODS
One step RT-PCR was performed with RNA from normal and ovarian cancer cell lines and 74 epithelial ovarian tumor tissues. AKAP-3-specific PCR product was amplified. The distribution of AKAP-3 expression and clinico-pathologic variables was analyzed. Survival distributions were estimated, and multivariate analyses were performed.


RESULTS
AKAP-3 mRNA expression was demonstrated in 43/74 (58%) of the ovarian cancer specimens. AKAP-3 was expressed in normal testis, but not in other normal tissues. AKAP-3 expression significantly correlated with increased likelihood of residual tumor (P = 0.005), but no increase in the likelihood of recurrence or persistent disease (P = 0.06). Patients with AKAP-3 mRNA expression were found to have a significantly poorer overall survival (median 50 months) compared with patients without AKAP-3 expression (median not reached) (P = 0.007). Multivariate analysis of AKAP-3 expression, residual disease, and response to frontline chemotherapy found response to be the strongest predictor of overall survival (P = 0.012).


CONCLUSIONS
Our data demonstrate that AKAP-3 is expressed at high frequency in patients with EOC. Since AKAP-3 demonstrates tumor-restricted expression and appears to be associated with worse overall survival, it could represent an attractive target for antigen-specific immunotherapy in EOC.
Sharma
Sameer
S
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Qian
Feng
F
Keitz
Bernadette
B
Driscoll
Deborah
D
Scanlan
Mathew J
MJ
Skipper
Jonathan
J
Rodabaugh
Kerry
K
Lele
Shashikant
S
Old
Lloyd J
LJ
Odunsi
Kunle
K
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate
D054758:A Kinase Anchor Proteins; C119530:AKAP3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger