Validating the impact of a molecular subtype in ovarian cancer on outcomes
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Validating the impact of a molecular subtype in ovarian cancer on outcomes : a study of the OVCAD Consortium. / Pils, Dietmar; Hager, Gudrun; Tong, Dan; Aust, Stefanie; Heinze, Georg; Kohl, Maria; Schuster, Eva; Wolf, Andrea; Sehouli, Jalid; Braicu, Ioana; Vergote, Ignace; Cadron, Isabelle; Mahner, Sven; Hofstetter, Gerda; Speiser, Paul; Zeillinger, Robert.
In: CANCER SCI, Vol. 103, No. 7, 01.07.2012, p. 1334-41.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Validating the impact of a molecular subtype in ovarian cancer on outcomes
T2 - a study of the OVCAD Consortium
AU - Pils, Dietmar
AU - Hager, Gudrun
AU - Tong, Dan
AU - Aust, Stefanie
AU - Heinze, Georg
AU - Kohl, Maria
AU - Schuster, Eva
AU - Wolf, Andrea
AU - Sehouli, Jalid
AU - Braicu, Ioana
AU - Vergote, Ignace
AU - Cadron, Isabelle
AU - Mahner, Sven
AU - Hofstetter, Gerda
AU - Speiser, Paul
AU - Zeillinger, Robert
N1 - © 2012 Japanese Cancer Association.
PY - 2012/7/1
Y1 - 2012/7/1
N2 - Most patients with epithelial ovarian cancer (EOC) are diagnosed at advanced stage and have a poor prognosis. However, a small proportion of these patients will survive, whereas others will die very quickly. Clinicopathological factors do not allow precise identification of these subgroups. Thus, we have validated a molecular subclassification as new prognostic factor in EOC. One hundred and ninety-four patients with Stage II-IV EOC were characterized by whole-genome expression profiling of tumor tissues and were classified using a published 112 gene set, derived from an International Federation of Gynecology and Obstetrics (FIGO) stage-directed supervised classification approach. The 194 tumor samples were classified into two subclasses comprising 95 (Subclass 1) and 99 (Subclass 2) tumors. All nine FIGO II tumors were grouped in Subclass 1 (P = 0.001). Subclass 2 (54% of advanced-stage tumors) was significantly correlated with peritoneal carcinomatosis and non-optimal debulking. Patients with Subclass 2 tumors had a worse overall survival for both serous and non-serous histological subtypes, as revealed by univariate analysis (hazard ratios [HR] of 3.17 and 17.11, respectively; P ≤ 0.001) and in models corrected for relevant clinicopathologic parameters (HR 2.87 and 12.42, respectively; P ≤ 0.023). Significance analysis of microarrays revealed 2082 genes that were differentially expressed in advanced-grade serous tumors of both subclasses and the focal adhesion pathway as the most deregulated pathway. In the present validation study, we have shown that, in advanced-stage serous ovarian cancer, two approximately equally large molecular subtypes exist, independent of classical clinocopathological parameters and presenting with highly different whole-genome expression profiles and a markedly different overall survival. Similar results were obtained in a small cohort of patients with non-serous tumors.
AB - Most patients with epithelial ovarian cancer (EOC) are diagnosed at advanced stage and have a poor prognosis. However, a small proportion of these patients will survive, whereas others will die very quickly. Clinicopathological factors do not allow precise identification of these subgroups. Thus, we have validated a molecular subclassification as new prognostic factor in EOC. One hundred and ninety-four patients with Stage II-IV EOC were characterized by whole-genome expression profiling of tumor tissues and were classified using a published 112 gene set, derived from an International Federation of Gynecology and Obstetrics (FIGO) stage-directed supervised classification approach. The 194 tumor samples were classified into two subclasses comprising 95 (Subclass 1) and 99 (Subclass 2) tumors. All nine FIGO II tumors were grouped in Subclass 1 (P = 0.001). Subclass 2 (54% of advanced-stage tumors) was significantly correlated with peritoneal carcinomatosis and non-optimal debulking. Patients with Subclass 2 tumors had a worse overall survival for both serous and non-serous histological subtypes, as revealed by univariate analysis (hazard ratios [HR] of 3.17 and 17.11, respectively; P ≤ 0.001) and in models corrected for relevant clinicopathologic parameters (HR 2.87 and 12.42, respectively; P ≤ 0.023). Significance analysis of microarrays revealed 2082 genes that were differentially expressed in advanced-grade serous tumors of both subclasses and the focal adhesion pathway as the most deregulated pathway. In the present validation study, we have shown that, in advanced-stage serous ovarian cancer, two approximately equally large molecular subtypes exist, independent of classical clinocopathological parameters and presenting with highly different whole-genome expression profiles and a markedly different overall survival. Similar results were obtained in a small cohort of patients with non-serous tumors.
KW - Adult
KW - European Union
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Kaplan-Meier Estimate
KW - Middle Aged
KW - Multivariate Analysis
KW - Neoplasm Grading
KW - Neoplasm Staging
KW - Neoplasms, Glandular and Epithelial
KW - Oligonucleotide Array Sequence Analysis
KW - Ovarian Neoplasms
KW - Prognosis
KW - Proportional Hazards Models
U2 - 10.1111/j.1349-7006.2012.02306.x
DO - 10.1111/j.1349-7006.2012.02306.x
M3 - SCORING: Journal article
C2 - 22497737
VL - 103
SP - 1334
EP - 1341
JO - CANCER SCI
JF - CANCER SCI
SN - 1347-9032
IS - 7
ER -