Abstract
ObjectiveTranscriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.MethodsGlobal gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset.Results5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged.ConclusionsThese data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.
Highlights
Epithelial ovarian tumors constitute a heterogeneous group of neoplasms that differ in epidemiology, genetic risk factors, precursor lesions and clinical behavior
Shared common features between ovarian and breast cancer may be useful for future development of predictive biomarkers and tailored treatments in both tumor types, and in this study we present interesting connections between the molecular subtypes of ovarian and breast cancer
Histologic subtype and grade were determined according to Silverberg and WHO [25,26] and all tumors were staged according to the International Federation of Gynecology and Obstetrics (FIGO) criteria
Summary
Epithelial ovarian tumors constitute a heterogeneous group of neoplasms that differ in epidemiology, genetic risk factors, precursor lesions and clinical behavior. Personalized therapy is called for in ovarian cancer since the histopathologic subtypes, as well as tumors with different malignant potential and tumor grade, can be viewed as separate diseases with differences related to both prognosis and treatment response [8,9,10,11,12]. Previous efforts to characterize ovarian cancers at the molecular level have identified distinct profiles related to the histologic subtypes and have suggested predictive gene signatures [13,14,15,16,17]. The C1–C2 and C4–C5 subtypes, in general, are thought to characterize high-grade serous tumors. The C3 signature represents low-grade serous and borderline tumors and the C6 signature low-grade, early-stage endometrioid tumors; in general they show good response to treatment and long-time survival [18]. Molecular subtyping in breast cancer is well established and recent reports have recognized similarities between high-grade serous ovarian cancer and basal-like breast cancer [19]
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