Maspin expression and localization impact on angiogenesis and prognosis in ovarian cancer.
BACKGROUND
The goal of this study is to evaluate the relation of maspin expression and its cellular localization to markers of angiogenesis in epithelial ovarian serous carcinoma (OSC).


METHODS
We identified 118 patients with high-grade advanced stage OSC who were treated at our institution. Clinical data were collected, and immunohistochemistry (IHC) with antibodies to VEGF, CD34, COX-2, and maspin was performed on paraffin-embedded tumor blocks. CD34 immunostaining was used to determine microvessel density. The correlation between the various molecular markers was assessed using the Chi-square test. Survival analysis was computed using the Kaplan-Meier model, and various prognostic variables were compared using Cox regression analysis.


RESULTS
Maspin expression was noted in 81.4% (96/118) of tumors. Expression was localized to the nuclear compartment in 21.2% of cases, whereas 60.2% of cases showed evidence of cytoplasmic +/- nuclear expression. Tumors that exhibited nuclear maspin expression had lower VEGF and COX-2 expression than tumors with negative or cytoplasmic expression. Tumors with high nuclear maspin expression had lower mean MVD than those with low or negative expression. The median survival based on localization of maspin was 1146 days for those with negative tumors, 1803 days for those with nuclear maspin, and 637 days for those with cytoplasmic maspin (P < 0.001). In a Cox regression analysis, maspin localization was an independent prognostic factor.


CONCLUSIONS
Maspin expression and localization seem to play a role in ovarian cancer angiogenesis and progression. High nuclear expression was associated with reduced markers of angiogenesis and prolonged survival.
Solomon
L A
LA
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wayne State University, Karmanos Cancer Institute, Harper Professional Building, 4160 John R St., Suite 2127, Detroit, MI 48201, USA.
Munkarah
A R
AR
Schimp
V L
VL
Arabi
M H
MH
Morris
R T
RT
Nassar
H
H
Ali-Fehmi
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D018284:Cystadenocarcinoma, Serous / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015843:Serpins / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
C085344:SERPIN-B5; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2