title: Gene expression-based classifications of fibroadenomas and phyllodes tumours of the breast.
abstract: Fibroepithelial tumors (FTs) of the breast are a heterogeneous group of lesions ranging from fibroadenomas (FAD) to phyllodes tumors (PT) (benign, borderline, malignant). Further understanding of their molecular features and classification might be of clinical value. In this study, we analysed the expression of 105 breast cancer-related genes, including the 50 genes of the PAM50 intrinsic subtype predictor and 12 genes of the Claudin-low subtype predictor, in a panel of 75 FTs (34 FADs, 5 juvenile FADs, 20 benign PTs, 5 borderline PTs and 11 malignant PTs) with clinical follow-up. In addition, we compared the expression profiles of FTs with those of 14 normal breast tissues and 49 primary invasive ductal carcinomas (IDCs). Our results revealed that the levels of expression of all breast cancer-related genes can discriminate the various groups of FTs, together with normal breast tissues and IDCs (False Discovery Rate < 5%). Among FTs, the levels expression of proliferation-related genes (e.g. CCNB1 and MKI67) and mesenchymal/epithelial-related (e.g. CLDN3 and EPCAM) genes were found to be most discriminative. As expected, FADs showed the highest and lowest expression of epithelial- and proliferation-related genes, respectively, whereas malignant PTs showed the opposite expression pattern. Interestingly, the overall profile of benign PTs was found more similar to FADs and normal breast tissues than the rest of tumours, including juvenile FADs. Within the dataset of IDCs and normal breast tissues, the vast majority of FADs, juvenile FADs, benign PTs and borderline PTs were identified as Normal-like by intrinsic breast cancer subtyping, whereas 7 (63.6%) and 3 (27.3%) malignant PTs were identified as Claudin-low and Basal-like, respectively. Finally, we observed that the previously described PAM50 risk of relapse prognostic score better predicted outcome in FTs than the morphological classification, even within PTs-only. Our results suggest that classification of FTs using gene expression-based data is feasible and might provide clinically useful biological and prognostic information.
authors: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129, 08035, Barcelona, Spain; Breast Cancer Unit, Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors: Maria
authors: M
authors: Vidal
authors: Pathology Department, Vall d'Hebron University Hospital, Pg Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
authors: Vicente
authors: V
authors: Peg
authors: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
authors: Patricia
authors: P
authors: Galván
authors: Department of Medical Oncology, Lozano Blesa University Hospital, San Juan Bosco, 15, 50009, Zaragoza, Spain.
authors: Alejandro
authors: A
authors: Tres
authors: Breast Cancer Unit, Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors: Javier
authors: J
authors: Cortés
authors: Pathology Department, Vall d'Hebron University Hospital, Pg Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
authors: Santiago
authors: S
authors: Ramón y Cajal
authors: Breast Cancer Surgical Oncology, Vall d'hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors: Isabel T
authors: IT
authors: Rubio
authors: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129, 08035, Barcelona, Spain; Breast Cancer Unit, Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: aprat@vhio.net.
authors: Aleix
authors: A
authors: Prat
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology; D005260:Female; D018226:Fibroadenoma / Q000145:classification / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D003557:Phyllodes Tumor / Q000145:classification / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D009363:Neoplasm Proteins
keywords: Fibroadenoma; Fibroepithelial; Gene expression; Intrinsic subtypes and claudin-low subtype; Juvenile fibroadenoma; Phyllodes tumours