Evaluation of cell surface expression of phosphatidylserine in ovarian carcinoma effusions using the annexin-V/7-AAD assay: clinical relevance and comparison with other apoptosis parameters.
Phosphatidylserine cell surface exposure during apoptosis can be detected by its binding to the protein annexin-V. We investigated annexin-V expression in 76 ovarian carcinoma effusions using flow cytometry. Results were analyzed for association with clinicopathologic parameters and survival. Annexin-V expression was additionally compared with the previously studied apoptotic markers cleaved caspase-3, cleaved caspase-8, and deoxyuridine triphosphate (dUTP) incorporation into DNA fragments. Annexin-V was expressed in all specimens and was more frequently detected compared with cleaved caspases and dUTP incorporation (P < .001). Annexin-V expression was higher in grade 3 vs grades 1 and 2 tumors (P = .014). A higher percentage of annexin-V-expressing cells in postchemotherapy specimens was associated with poor overall (P = .005) and progression-free (P = .013) survival. We present the first evidence of annexin-V expression in ovarian carcinoma effusions. The higher annexin-V expression compared with other apoptosis parameters and its association with high-grade disease and poor survival in postchemotherapy patients suggest a role in cell survival rather than apoptosis in effusions.
Division of Pathology, Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello N-0310 Oslo, Norway.
Hiep Phuc
HP
Dong
Arild
A
Holth
Lilach
L
Kleinberg
Marit Gunhild
MG
Ruud
Mari Bunkholt
MB
Elstrand
Claes G
CG
Tropé
Ben
B
Davidson
Björn
B
Risberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000096:biosynthesis*; D017209:Apoptosis / Q000502:physiology; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010718:Phosphatidylserines / Q000096:biosynthesis*; D016066:Pleural Effusion, Malignant / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
D017304:Annexin A5; D014408:Biomarkers, Tumor; D010718:Phosphatidylserines; D053148:Caspase 3; D020170:Caspase 1