TY - JOUR
T1 - Maspin expression in epithelial ovarian cancer and associations with poor prognosis
T2 - A Gynecologic Oncology Group study
AU - Secord, Angeles Alvarez
AU - Lee, Paula S.
AU - Darcy, Kathleen M.
AU - Havrilesky, Laura J.
AU - Grace, Lisa A.
AU - Marks, Jeffrey R.
AU - Berchuck, Andrew
N1 - Funding Information:
This study was supported by the American Association of Obstetricians and Gynecologists Foundation, and National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office along with the GOG Tissue Bank (CA 27469) and to the GOG Statistical and Data Center (CA 37517). The following GOG member institutions participated in this translational research study: University of Minnesota Medical School, University of Mississippi Medical Center, University of California at Los Angeles, University of Washington, Milton S. Hershey Medical Center, Georgetown University Hospital, University of Cincinnati, University of North Carolina School of Medicine, University of Texas Southwestern Medical Center at Dallas, Indiana University Medical Center, Wake Forest University School of Medicine, University of California Medical Center at Irvine, University of Kentucky, The Cleveland Clinic Foundation, SUNY at Stony Brook, Southwest Oncology Group, Washington University School of Medicine, Columbus Cancer Council, University of Massachusetts Medical Center, Medical University of South Carolina, University of Oklahoma, and Tacoma General Hospital.
PY - 2006/6
Y1 - 2006/6
N2 - Objective: This study examined MASPIN expression in human ovarian cancer, and explored the association between MASPIN and prognosis in patients with advanced stage disease treated with first-line cisplatin, carboplatin and/or paclitaxel. Methods: Frozen primary tumors were obtained from 68 women with previously untreated, advanced stage epithelial ovarian cancer who participated in a specimen banking protocol and a phase III treatment trial conducted by the Gynecologic Oncology Group. Immunoblot analysis was performed in lysates prepared from these tumor specimens to quantify the relative expression of MASPIN/β-actin. Results.: MASPIN was expressed at detected levels in 49 (72%) cases with relative expression ranging from 0.02 to 7.7 (median = 0.2), and was not detected in 19 (28%) of the primary tumors tested. Non-detectable levels of this class II tumor suppressor gene product and inhibitor of angiogenesis were associated with suboptimally-debulked disease (P = 0.034) but not with patient age, FIGO stage, tumor grade, or histologic subtype. After adjusting for prognostic variables for disease progression or death, non-detectable MASPIN expression predicted an increased risk of disease progression (hazard ratio [HR] = 1.89; 95% confidence interval [CI]: 1.04-3.45; P = 0.038) and death (HR = 1.99; 95% CI: 1.07-3.69; P = 0.030). Conclusions: In advanced stage epithelial ovarian cancer, non-detectable MASPIN appears to be associated with suboptimally-debulked disease and be an independent predictor of an increased risk of progression and death. Further studies are needed to validate these exploratory findings, determine the molecular mechanism controlling MASPIN expression as well as down-regulation and loss in ovarian cancer, and determine if MASPIN can prevent progression of this disease.
AB - Objective: This study examined MASPIN expression in human ovarian cancer, and explored the association between MASPIN and prognosis in patients with advanced stage disease treated with first-line cisplatin, carboplatin and/or paclitaxel. Methods: Frozen primary tumors were obtained from 68 women with previously untreated, advanced stage epithelial ovarian cancer who participated in a specimen banking protocol and a phase III treatment trial conducted by the Gynecologic Oncology Group. Immunoblot analysis was performed in lysates prepared from these tumor specimens to quantify the relative expression of MASPIN/β-actin. Results.: MASPIN was expressed at detected levels in 49 (72%) cases with relative expression ranging from 0.02 to 7.7 (median = 0.2), and was not detected in 19 (28%) of the primary tumors tested. Non-detectable levels of this class II tumor suppressor gene product and inhibitor of angiogenesis were associated with suboptimally-debulked disease (P = 0.034) but not with patient age, FIGO stage, tumor grade, or histologic subtype. After adjusting for prognostic variables for disease progression or death, non-detectable MASPIN expression predicted an increased risk of disease progression (hazard ratio [HR] = 1.89; 95% confidence interval [CI]: 1.04-3.45; P = 0.038) and death (HR = 1.99; 95% CI: 1.07-3.69; P = 0.030). Conclusions: In advanced stage epithelial ovarian cancer, non-detectable MASPIN appears to be associated with suboptimally-debulked disease and be an independent predictor of an increased risk of progression and death. Further studies are needed to validate these exploratory findings, determine the molecular mechanism controlling MASPIN expression as well as down-regulation and loss in ovarian cancer, and determine if MASPIN can prevent progression of this disease.
KW - Angiogenesis
KW - Biomarker
KW - MASPIN
KW - Ovarian carcinoma
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=33646718965&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2006.02.014
DO - 10.1016/j.ygyno.2006.02.014
M3 - Article
C2 - 16551475
AN - SCOPUS:33646718965
SN - 0090-8258
VL - 101
SP - 390
EP - 397
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -