MED12,TERTandRARAin fibroepithelial tumours of the breast

Abstract

<jats:p>Fibroepithelial tumours are biphasic neoplasms of the breast comprising the common benign fibroadenomas and the less common phyllodes tumours (PTs), which have recurrent potential. PTs are classified into benign, borderline or malignant, based on five histopathological criteria, with malignant PTs having the highest metastatic capability. Accurate diagnosis can be challenging due to the subjective assessment of histopathological parameters. Fibroadenomas bear morphological similarities to benign PTs, while borderline and malignant PTs can sometimes be difficult to distinguish from other spindle cell tumours of the breast. From clonality studies to whole-genome sequencing, much research has been conducted to elucidate the molecular pathogenesis of fibroepithelial tumours, which, in turn, have allowed leveraging the findings for diagnostic applications, including grading of PTs. The most noteworthy discovery was of recurrent <jats:italic>MED12</jats:italic> mutations in both fibroadenomas and PTs. Subsequent studies also uncovered relatively frequent genetic mutations in <jats:italic>TERT</jats:italic> promoter and <jats:italic>RARA</jats:italic>. A customised panel of 16 most frequently mutated genes in fibroepithelial tissues has been compiled previously and has contributed to resolving a few diagnostic dilemmas. This review will introduce the 16 genes and focus on the top three that are most frequently mutated in fibroepithelial tumours: <jats:italic>MED12</jats:italic>, <jats:italic>TERT</jats:italic>, and <jats:italic>RARA</jats:italic>.</jats:p>

A huge malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report

“…A growing number of studies have suggested its mechanism. Several gene mutations were found in fibroepithelial neoplasms such as MED12, TERT, and RARA which were commonly occurred (6). Clinically, PTs tend to grow quickly.…”

Metaplastic carcinomas of the breast without evidence of epithelial differentiation: a diagnostic approach for management

“…Most studies on what has been labelled 'breast sarcoma' have included a mix of tumours, so a conclusion on the outcome and response to chemotherapy of specific subtypes is not possible (with the exception of the well-established phyllodes tumours and mammary angiosarcoma). 25,28,46,47,49 For example, one previous study, which set out to compare the outcome of 'primary breast sarcomas' versus phyllodes tumours, included 12 cases of carcinosarcoma (34%), currently considered as variants of MBC. In that series, lymph node metastasis was reported in 11% of patients and adjuvant chemotherapy was offered to 63%.…”

“…There is some clinical uncertainty concerning whether MBC lacking evidence of epithelial differentiation should be treated as sarcoma and managed by specialised sarcoma teams 31,44,45 or treated using the same principles as conventional invasive breast carcinoma, a dilemma that prompted this study. Most studies on what has been labelled ‘breast sarcoma’ have included a mix of tumours, so a conclusion on the outcome and response to chemotherapy of specific subtypes is not possible (with the exception of the well‐established phyllodes tumours and mammary angiosarcoma) 25,28,46,47,49 . For example, one previous study, which set out to compare the outcome of ‘primary breast sarcomas’ versus phyllodes tumours, included 12 cases of carcinosarcoma (34%), currently considered as variants of MBC.…”

Updates on Lobular Neoplasms and Papillary, Adenomyoepithelial, and Fibroepithelial Lesions of the Breast

“…There has been significant progress in understanding the molecular changes in FEL, which helps not only in better understanding of the relationships among different types of FEL, but also in making more accurate diagnosis. 98 There are 2 major molecular pathways in the development of FELs. One pathway is driven by mediator complex subunit 12 (MED12) mutations that are associated with TERT mutations; the other pathway is driven by other gene mutations, including P53, PIK3CA, or EGFR, and so on, in MED12 wildtype FELs.…”