TY - JOUR
T1 - Prognostic relevance of carbonic anhydrase-IX in high-risk, early-stage cervical cancer
T2 - A Gynecologic Oncology Group study
AU - Liao, Shu Yuan
AU - Darcy, Kathleen M.
AU - Randall, Leslie M.
AU - Tian, Chunqiao
AU - Monk, Bradley J.
AU - Burger, Robert A.
AU - Fruehauf, John P.
AU - Peters, William A.
AU - Stock, Richard J.
AU - Stanbridge, Eric J.
N1 - Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469 ), the GOG Tissue Bank (CA 27469 , CA 11479 ), and to the GOG Statistical and Data Center (CA 37517 ). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Walter Reed Medical Center, Wayne State University, University of Southern California at Los Angeles, University of Pennsylvania Cancer Center, University of Miami School of Medicine, Milton S. Hershey Medical Center, Georgetown University Hospital, University of Cincinnati, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, 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, Tufts-New England Medical Center, Rush University Medical Center, SUNY Downstate Medical Center, Eastern Virginia Medical School, Johns Hopkins Cancer Center, State University of New York at Stony Brook, Washington University School of Medicine, Cooper Hospital/University Medical Center, Columbus Cancer Council, M. D. Anderson Cancer Center, University of Massachusetts Medical School, Fox Chase Cancer Center, Women's Cancer Center, University of Oklahoma, University of Virginia Health Sciences Center, University of Chicago, University of Arizona, and Case Western Reserve University.
PY - 2010/3
Y1 - 2010/3
N2 - Objectives: This study aimed to determine whether carbonic anhydrase-IX (CA-IX) was associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated with adjuvant pelvic radiotherapy with or without radiosensitizing chemotherapy. Methods: CA-IX expression was detected using an immunohistochemistry assay and categorized as low when ≤ 80% of tumor cells exhibited CA-IX staining and high when > 80% tumor cells display CA-IX staining. Associations between CA-IX expression and clinical characteristics, angiogenesis marker expression, and clinical outcome were evaluated. Results: High CA-IX expression was observed in 35/166 (21.1%) of cases. CA-IX expression was not associated with age, race, stage, cell type, grade, positive margins, parametrial extensions, positive lymph nodes, or lymphovascular space invasion but was associated with tumor size categorized as < 2 , 2-2.9 , or ≥ 3 cm (high expression: 4.7% vs. 23.2% vs. 32.5%, P = 0.003) and cervical invasion confined to the inner two-thirds compared with the outer third of the cervix (high expression: 6.1% vs. 23.7%, P = 0.028). CA-IX expression was not associated with immunohistochemical expression of p53, CD31, CD105, thrombospondin-1, or vascular endothelial growth factor-A. Women with high versus low CA-IX expression had similar PFS (P = 0.053) and significantly worse OS (P = 0.044). After adjusting for prognostic clinical covariates, high CA-IX expression was an independent prognostic factor for PFS (hazard ratio [HR] = 2.12; 95% confidence interval [CI] = 1.13-3.95; P = 0.019) and OS (HR = 2.41; 95% CI = 1.24-4.68; P = 0.009). Conclusions: Tumor hypoxia measured by immunohistochemical expression of CA-IX is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer.
AB - Objectives: This study aimed to determine whether carbonic anhydrase-IX (CA-IX) was associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated with adjuvant pelvic radiotherapy with or without radiosensitizing chemotherapy. Methods: CA-IX expression was detected using an immunohistochemistry assay and categorized as low when ≤ 80% of tumor cells exhibited CA-IX staining and high when > 80% tumor cells display CA-IX staining. Associations between CA-IX expression and clinical characteristics, angiogenesis marker expression, and clinical outcome were evaluated. Results: High CA-IX expression was observed in 35/166 (21.1%) of cases. CA-IX expression was not associated with age, race, stage, cell type, grade, positive margins, parametrial extensions, positive lymph nodes, or lymphovascular space invasion but was associated with tumor size categorized as < 2 , 2-2.9 , or ≥ 3 cm (high expression: 4.7% vs. 23.2% vs. 32.5%, P = 0.003) and cervical invasion confined to the inner two-thirds compared with the outer third of the cervix (high expression: 6.1% vs. 23.7%, P = 0.028). CA-IX expression was not associated with immunohistochemical expression of p53, CD31, CD105, thrombospondin-1, or vascular endothelial growth factor-A. Women with high versus low CA-IX expression had similar PFS (P = 0.053) and significantly worse OS (P = 0.044). After adjusting for prognostic clinical covariates, high CA-IX expression was an independent prognostic factor for PFS (hazard ratio [HR] = 2.12; 95% confidence interval [CI] = 1.13-3.95; P = 0.019) and OS (HR = 2.41; 95% CI = 1.24-4.68; P = 0.009). Conclusions: Tumor hypoxia measured by immunohistochemical expression of CA-IX is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer.
KW - Carbonic anhydrase-IX
KW - Cervical cancer
KW - GOG
UR - http://www.scopus.com/inward/record.url?scp=75749122186&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2009.10.062
DO - 10.1016/j.ygyno.2009.10.062
M3 - Article
C2 - 19913895
AN - SCOPUS:75749122186
SN - 0090-8258
VL - 116
SP - 452
EP - 458
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -