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Validating the Impact of a Molecular Subtype in Ovarian Cancer on Outcomes – A Study of the OVCAD Consortium - Pils - Cancer Science -
Abstract
The
majority of patients with epithelial ovarian cancer (EOC) is diagnosed
at advanced stage and has a poor prognosis. A small proportion of these
patients though will survive while others 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
ninety-four patients with stage II to IV EOC were characterized by
whole-genome expression profiling of tumor tissues and classified using a
published 112 gene-set, derived from a FIGO stage directed supervised
classification approach.
The 194 tumor
samples were classified into two subclasses of 95 (subclass 1) and 99
(subclass 2) tumors, grouping all 9 FIGO II tumors in subclass 1
(p=0.001). Subclass 2 (54% of advanced stage tumors) correlated
significantly with peritoneal carcinomatosis and non-optimal debulking.
Patients with subclass 2 tumors had a worse overall survival in both
histological subtypes both, univariate (HRs 3.17 (serous) and 17.11
(non-serous), p≤0.001) and in models corrected for relevant
clinicopathologic parameters (HRs 2.87 (serous) and 12.42 (non-serous),
p≤0.023). Significance analysis of microarrays revealed 2,082 genes
differentially expressed in advanced grade serous tumors of both
subclasses and the focal adhesion pathway as the most deregulated
pathway.
In this validation study we
showed that in advanced-stage serous ovarian cancer two approximately
equally large molecular subtypes exist, independent from classical
clinocopathological parameters presenting with highly different whole
genome expression profiles and an impressively different overall
survival. Similar results were obtained in a small cohort of patients
with non-serous tumors.
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