Histopathologic, immunophenotypic, and proteomics characteristics of low-grade phyllodes tumor and fibroadenoma: more similarities than differences

Zhang, Lingxin; Yang, Chen; Pfeifer, John D.; Caprioli, Richard M.; Judd, Audra M.; Patterson, Nathan Heath; Reyzer, Michelle L.; Norris, Jeremy L.; Maluf, Horacio

doi:10.1038/s41523-020-0169-8

Cited by 26 publications

(15 citation statements)

References 40 publications

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“…Although broadenomas and benign phyllodes tumors are recognized as distinct entities, their common overlapping histologic features (particularly between cellular FA and benign PT) makes the distinction challenging in daily practice. There are several comprehensive genetic and proteomic studies of FELs suggests that FAs and benign PTs share similar gene and protein expression pro le (9,10,18,23). Our study revealed that broadenomas (FAs), cellular broadenomas, and benign phyllodes tumors (PTs) manifest similar gene expression pro les.…”

Section: Discussionmentioning

confidence: 66%

“…In recent years, a wide range of studies have been performed on PTs and FAs with respect to their biomarker expression, genetic alterations, and molecular mechanisms, as potential tools to more reproducibly classify PTs and FAs (9)(10)(11). Gene expression pro ling is an additional approach which might help predict the biological behavior of FELs and provide insights for their clinical management, though studies using this technique remain limited.…”

Section: Introductionmentioning

confidence: 99%

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Gene Expression Profiling of Fibroepithelial Lesions of the Breast

Vail

Maluf

et al. 2022

Preprint

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Fibroepithelial lesions of the breast (FELs) are a heterogeneous group of neoplasms exhibiting a histologic spectrum ranging from fibroadenomas (FAs) to malignant phyllodes tumors (PTs). Despite published histologic criteria for their classification, it is common for such lesions to exhibit overlapping features, leading to subjective interpretation and inter-observer disagreements in histologic diagnosis. Therefore, there is a need for a more objective diagnostic modality to aid in the accurate classification of these lesions and to guide appropriate clinical management. In this study, the expression of 750 tumor-related genes was measured in a cohort of 34 FELs (5 FAs, 9 cellular FAs, 9 benign PTs, 7 borderline PTs, and 4 malignant PTs). Differentially expressed gene analysis, gene set analysis, pathway analysis, and cell type analysis were performed. Genes involved in matrix remodeling and metastasis (e.g., MMP9, SPP1, COL11A1), angiogenesis (VEGFA, ITGAV, NFIL3, FDFR1, CCND2), hypoxia (ENO1, HK1, CYBB, HK2), metabolic stress (e.g., UBE2C, CDKN2A, FBP1), cell proliferation (e.g., CENPF, CCNB1), PI3K-Akt pathway (e.g., ITGB3, NRAS) were highly expressed in malignant PTs and less expressed in borderline PTs, benign PTs, cellular FAs, and FAs. The overall gene expression profiles of benign PTs, cellular FAs, and FAs were very similar. Although a slight difference was observed between borderline and benign PTs, a higher degree of difference was observed between borderline and malignant PTs. Additionally, the macrophage cell abundance scores and CCL5 were significantly higher in malignant PTs compared with all other groups. Our results suggest that the gene expression profiling-based approach could lead to further stratification of FELs and may provide clinically useful biological and pathophysiological information to improve the existing histologic diagnostic algorithm.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of Fibroepithelial Lesions of the Breast

Vail

Maluf

et al. 2022

Preprint

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“…Recent studies showed that fibroadenomas, benign and some borderline phyllodes tumors share similar clinical features, immunohistochemical patterns, genetic aberrations, and outcomes. 2,3 For those lesions in which a definitive distinction between fibroadenoma and phyllodes tumor is difficult or not possible, some researchers suggested avoiding the diagnosis of phyllodes tumor and choosing a more conservative surgical approach. 2 It is generally acknowledged that the recurrence rate of phyllodes tumors is higher than that of fibroadenomas.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 For those lesions in which a definitive distinction between fibroadenoma and phyllodes tumor is difficult or not possible, some researchers suggested avoiding the diagnosis of phyllodes tumor and choosing a more conservative surgical approach. 2 It is generally acknowledged that the recurrence rate of phyllodes tumors is higher than that of fibroadenomas. 4 Most fibroadenomas do not recur after complete excision, although there is a tendency to develop same-site recurrence after excision in adolescents and young adults.…”

Section: Introductionmentioning

confidence: 99%

MED12 exon 2 and TERT promoter mutations in primary and recurrent breast fibroepithelial lesions

Wang

et al. 2021

Pathology International

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The genetic alterations in the recurrent breast fibroepithelial tumors are poorly understood. In the present study, we aimed to investigate mediator protein complex subunit 12 (MED12) exon 2 and telomerase reverse transcriptase (TERT) promoter mutations in a series of primary and recurrent fibroepithelial tumors. Sanger sequencing for MED12 exon 2 and TERT promoter was performed in 26 pairs of primary and recurrent fibroepithelial tumors (19 pairs of phyllodes tumors and seven pairs of fibroadenomas). The relationship between the genotypes and clinicopathological variables was also analyzed. MED12 mutation was identified in 19 primary tumors (12 phyllodes tumors and 7 fibroadenomas) and 17 recurrences (14 phyllodes tumors and three fibroadenomas). Most recurrent phyllodes tumors retained the original MED12 variants (17/19). Six recurrent fibroadenomas showed different MED12 variants from their paired primary tumors (6/7). TERT promoter mutation was identified in 13 primary phyllodes tumors (13/19) and 15 recurrent phyllodes tumors (15/19). However, it was only identified in one primary fibroadenoma (1/7). Recurrent phyllodes tumors often retained the original MED12 and TERT promoter mutations, while recurrent fibroadenomas often acquired new MED12 mutations. Our findings suggest that recurrent phyllodes tumors may be "true recurrence," and TERT mutant "benign fibroepithelial tumors" should be treated as phyllodes tumors.

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“…Phyllodes tumours are uncommon fibroepithelial breast tumours that are capable of a wide range of biological behaviours, from benign to malignant [1]. They can appear at any age, with a median age of presentation of 42 to 45 years, and are often misdiagnosed as fibroadenomas [2,3]. Phyllodes tumours account for less than 1% of all breast tumours, and they rarely undergo a malignant epithelial transformation.…”

Section: Introductionmentioning

confidence: 99%