The paradoxical expression of maspin in ovarian carcinoma.
Maspin is a noninhibitory member of the serpin family that is down-regulated in breast carcinoma but overexpressed in pancreatic carcinoma. There are no published data regarding the role of maspin in ovarian carcinoma, which is the focus of the present study. Ovarian cell lines (normal and cancer) and tumors (80 invasive, 14 benign, and 10 low malignant potential) were evaluated for maspin expression and localization. Normal ovarian surface epithelial cells had low levels of maspin. Two of four ovarian cancer cell lines (OVCAR3 and SKOV3) expressed maspin, whereas the cell line EG had weak expression, and 222 had no detectable maspin. Subcellular fractionation studies revealed that the two maspin-positive ovarian cancer cell lines contained maspin in both the nuclear and cytosolic compartments. Wild-type maspin was transfected into the aggressive ovarian cancer cell lines SKOV3 and 222. The in vitro invasive activity of the maspin-transfected cell lines was 44-68% lower than respective controls. The histopathology analysis revealed that among the ovarian tumors examined, 57 (71%) were ranked positive for maspin. Thirty (37%) of the invasive tumors overexpressed maspin. Invasive cancers were more likely to have predominantly cytoplasmic staining compared with benign and low-malignant-potential tumors. Maspin overexpression was significantly associated with a high tumor grade (P = 0.004), the presence of ascites (P = 0.02), a lower likelihood of optimal surgical cytoreduction (P = 0.04), and a shorter duration of overall survival (median survival, 6.33 versus 2.67 years; P = 0.003). The Cox proportional hazards multivariate model revealed that maspin overexpression and high stage were independent predictors of survival. Thus, maspin was found to be overexpressed in a substantial proportion of ovarian tumors, which may serve as an adverse prognostic factor; however, its localization may provide new clues as to its activity and function. These paradoxical results may offer new insights regarding the role of maspin in ovarian cancer progression that may also impact diagnosis and treatment strategies.
Sood
Anil K
AK
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242-1109, USA. anil-sood@uiowa.edu
Fletcher
Mavis S
MS
Gruman
Lynn M
LM
Coffin
Jeremy E
JE
Jabbari
Sarvenaz
S
Khalkhali-Ellis
Zhila
Z
Arbour
Nancy
N
Seftor
Elisabeth A
EA
Hendrix
Mary J C
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane; D002467:Cell Nucleus / Q000201:enzymology; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology; D004273:DNA, Neoplasm / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005816:Genetic Complementation Test; D006801:Humans; D015993:Life Tables; D008567:Membranes, Artificial; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000201:enzymology
D004273:DNA, Neoplasm; D008567:Membranes, Artificial; D009363:Neoplasm Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C085344:SERPIN-B5; D015843:Serpins