Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large patient cohort

Chng, Tze Wei; Gudi, Mihir; Lim, Swee Ho; Li, Huihua; Tan, Puay Hoon

doi:10.1136/jclinpath-2017-204568

Cited by 28 publications

(12 citation statements)

References 19 publications

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“…Multiple studies have investigated the relationship between FAs and PTs, with some authors noting comparable clonality , similar allelic loss at locus D7S522 , and highly recurrent MED12 mutations . There have also been documented reports on the presence of FA‐like areas in PTs , cases of synchronous FA and PT, along with patients with FA having subsequent PT after a period of time, albeit this remains a rare occurrence . Such findings support theories of both tumours sharing similar origin and aetiology, with recent studies unveiling their mutational and gene expression profiles .…”

Section: Introductionmentioning

confidence: 65%

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Nasir

Rajasegaran

et al. 2019

The Journal of Pathology

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Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles.Conflict of interest statement: PHT, BTT, and PT jointly hold patent applications for PCT/SG2015/050107 (Breast fibroadenoma susceptibility mutations and use thereof) and PCT/SG2015/050368 (Method and kit for pathologic grading of breast neoplasms). The other authors declare no competing interests.

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Section: Introductionmentioning

confidence: 65%

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Nasir

Rajasegaran

et al. 2019

The Journal of Pathology

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“…Its widespread use in clinical practice is limited by the rarity of PTs in general. Nevertheless, it is being further validated in 2 larger cohorts [37,38]. Although several studies have looked into the various factors that may predict distant metastasis of PTs, none were successfully established and universally recognised as reliable predictors of PT metastasis, in part due to the limited number of such events.…”

Section: Factors Associated With Metastasismentioning

confidence: 99%

Distant metastases in phyllodes tumours of the breast: an overview

2017

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Phyllodes tumours (PTs) of the breast are uncommon fibroepithelial neoplasms, comprising 0.3 -1.0% of all primary breast malignancies in Western countries, but accounting for a higher proportion of primary breast tumours in Asian countries. They are graded as benign, borderline or malignant based on the World Health Organisation (WHO) classification, according to a constellation of 5 histologic parameters. While most PTs carry a good prognosis, malignant and occasionally borderline PTs have the potential to metastasize to distant sites. Although events of distant metastasis are few, the prognosis for such patients is dismal, as they are often unresponsive to chemotherapy with high mortality. This review seeks to provide an overview of this rare but important phenomenon of distant metastases in PTs of the breast.

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“…Although the epithelial component showed a different expression pattern–an inverse correlation with stromal expression–we focused on the stromal component in the present study because the stromal component is the neoplastic element and determines the diagnosis and tumor grade. Although PTs account for a far lesser proportion of breast fibroepithelial lesions compared to fibroadenomas, both lesions share histomorphological features [ 20 , 21 ], as well as genetic alterations such as recurrent MED12 mutations [ 7 , 22 – 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…share histomorphological features [20,21], as well as genetic alterations such as recurrent MED12 mutations [7,[22][23][24].…”

Section: Plos Onementioning

confidence: 99%

Expression of EMP1, EMP2, and EMP3 in breast phyllodes tumors

Jin

Koo

2020

PLoS ONE

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Phyllodes tumors (PTs) are biphasic tumors accounting for 0.3-1.5% of all breast tumors. Epithelial membrane proteins (EMPs) have been reported in various malignant tumors but their expression in PTs is unclear. In this study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in breast phyllodes tumors (PTs), and to investigate their clinical implications. Methods In total, 185 PTs were used for constructing a tissue microarray. Immunohistochemical staining for EMP1, EMP2, and EMP3 was performed, and the results were analyzed along with the clinicopathologic parameters. Results In total, 185 PTs were included in this study, and comprised 138 benign, 32 borderline, and 15 malignant PTs. In malignant PTs, the epithelial component showed decreased expression of EMP1 (P = 0.027), EMP2 (P = 0.004), and EMP3 (P = 0.032), compared to the benign and borderline PTs. Conversely, stromal component of borderline and malignant PTs showed higher expression of EMP1 (P = 0.027), EMP2 (P = 0.004), and EMP3 (P = 0.032) compared to benign PTs. Expression of EMP1 and EMP3 correlated positively with stromal cellularity and cellular atypia (P < 0.001). In the univariate analysis, stromal EMP3 was associated with shorter disease-free survival (P < 0.001), and shorter overall survival (P = 0.034). Conclusion The expression of EMP1, EMP2, and EMP3 is decreased in the epithelial component and is increased in the stromal component of PT with higher histologic grade. Thus, stromal EMP3 expression may serve as an independent prognostic factor in PT.

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Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large patient cohort

Cited by 28 publications

References 19 publications

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Distant metastases in phyllodes tumours of the breast: an overview

Expression of EMP1, EMP2, and EMP3 in breast phyllodes tumors

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