p53 Protein Expression and Gene Mutation in Phyllodes Tumors of the Breast

Gatalica, Zoran; Finkelstein, S. D.; Lucio, Emmanuel; Tawfik, Ossama; Palazzo, Juan; Hightower, Barbara; Eyzaguirre, Eduardo

doi:10.1078/0344-0338-00031

Cited by 29 publications

(19 citation statements)

References 21 publications

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“…1,17 It is stated that p53 immunohistochemical expression in stromal cells can be relied upon as an adjunctive tool in the diagnosis of malignancy in phyllodes tumors. 24,25 In our study, p53 staining was correlated with grade, with contributions from stromal hypercellularity and overgrowth, but did not reveal an association with recurrent disease, corroborating the conclusions of other authors, and supporting its potential use as a confirmatory marker of malignancy in these tumors. Interestingly, p53 immunohistochemical positivity was also noted in a proportion of luminal epithelial and myoepithelial cells in our series.…”

Section: Discussionsupporting

confidence: 90%

“…While studies on p53 and c-kit have predominantly dealt with protein expression using immunohistochemistry, it will be useful to validate these findings at the molecular level in order to determine specific genetic abnormalities in the responsible genes. Sequencing of the p53 gene carried out by various authors has discovered mostly mutations, 16,24 although one study disclosed a wild-type gene sequence in a malignant phyllodes tumor. 32 Proliferative activity using Mib-1 and S-phase fraction, 19,27 microvessel density, 25 CD34 and factor XIIIa stromal positivity 33 are also believed to be potentially helpful in predicting phyllodes tumor behavior, although their clinical relevance remains to be further ratified.…”

Section: Discussionmentioning

confidence: 99%

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p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study

et al. 2005

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Breast phyllodes tumors are fibroepithelial neoplasms whose clinical behavior is difficult to predict on histology. There is relatively scant data on the role of biological markers. In this study, we determined if p53 and CD117 (c-kit) protein expression was predictive of behavior in a series of 335 phyllodes tumors diagnosed at the Singapore General Hospital, using immunohistochemistry on tissue microarrays. Representative areas from 250 (75%) benign, 54 (16%) borderline and 31 (9%) malignant phyllodes tumors were selected for construction of tissue microarrays using the 2 mm punch. Immunohistochemistry for p53 and CD117 was carried out using the streptavidin-biotin method. Staining proportion and intensity of both epithelial and stromal elements were analyzed. p53 immunostaining was observed in the epithelium of 28 (10%) of 278 microarrays; myoepithelium of 53 (21%) of 251 microarrays; and stromal cells in 105 (36%) of 289 microarrays. CD117 immunohistochemical reactivity was noted in epithelial and stromal components of 175 (of 267, 66%) and 17 (of 273, 6%) microarrays, respectively. Stromal p53 and CD117 protein expression was associated with tumor grade (Po0.05). Of 43 (13%) women who suffered recurrences during the follow-up period, CD117 stromal staining predicted recurrent disease (Po0.05), but p53 was not correlative. We conclude that tissue microarrays are a convenient method for evaluating immunostaining results of large numbers of phyllodes tumors. Although positive p53 stromal immunohistochemical detection may corroborate histologic malignancy, it is CD117 protein expression in phyllodes tumor stromal cells that may be of potential utility in predicting recurrent disease.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study

et al. 2005

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“…The expression of these markers is reportedly higher in PT than in FA, and they progress from benign or borderline to malignant PT [26]. In addition, the TP53 mutation is also reported to be associated with malignant PT [27]. These results suggest that the additional genetic change(s) to MED12 is required for FA to transform to PT.…”

Section: Discussionmentioning

confidence: 82%

Mutational analysis of MED12 in fibroadenomas and phyllodes tumors of the breast by means of targeted next-generation sequencing

Mishima

Kagara

Tanei

et al. 2015

Breast Cancer Res Treat

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We aimed to analyze MED12 mutation in fibroadenomas (FAs) and phyllodes tumors (PTs) of the breast, which are closely related and consist of epithelial and stromal components. Targeted deep-sequencing using next-generation sequencing was performed in FAs (n = 58) and PTs (n = 27). The frequency of MED12 mutant tumors was significantly higher (P = 0.016) in PTs (74.1 %) than in FAs. (46.6 %). As for FAs, this frequency was significantly higher (P = 0.001) for intracanalicular type (69.0 %) than for other histological subtypes such as pericanalicular, organoid, and mastopathic types (24.1 %). Laser microdissection study revealed that stromal cells, but not epithelial cells, harbored MED12 mutations in both FAs and PTs. MED12 mutation is implicated in the pathogenesis of both FAs and PTs. The similarly high frequency of MED12 mutation in intracanalicular type FAs suggests that they are most closely related to PTs. It is thus speculated that FAs with MED12 mutation are more likely to progress to PTs.

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“…17 Other molecular studies showed that somatic or germinal mutations of TP53 were present in isolated cases of malignant phyllodes tumors. 18,19 Expression of P53 was associated with histological features of malignancy, but did not predict outcome. 20 The Wnt pathway (bcatenin overexpression) and the IGF pathway could play a role in the development of these neoplasms.…”

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confidence: 90%

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

et al. 2007

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Phyllodes tumors are rare fibroepithelial tumors of the breast. The pathologic grading of phyllodes tumors based on the aspect of the stromal component, is divided into 2 or 3 grades according to the system used. To determine whether genetic markers could be of use for improving the classification of phyllodes tumors and to provide a better knowledge of the genetic alterations in these tumors, we analyzed chromosomal changes detected by comparative genomic hybridization (CGH) in comparison with histological data, in a series of 30 cases. Recurrent chromosome imbalances were observed in 55, 91 and 100% of benign, borderline and malignant phyllodes tumors, respectively. The mean number of chromosome changes was one in benign, six in borderline, and six in malignant phyllodes tumors. Most frequent genetic imbalances were þ 1q (12/30), À13q (7/30), À6q (9/30), þ 5 (9/30) and À10p (8/30). Gains of 1q, present in only one of nine benign tumors, were found in 11/21 (51%) borderline or malignant tumors. Losses of 13q have 13q14.2 as smallest region of overlap, suggesting that the RB1 gene could be the target of deletions. Amplifications of 12q14, involving the MDM2 locus, and of 8p24, involving the MYC gene, were observed in one case each. Borderline and malignant phyllodes tumors could not be differentiated on the basis of their genomic imbalances (presence and number of chromosomal changes, presence of 1q gain and/or 13q loss). Conversely, benign tumors could be significantly differentiated from the group composed of borderline and malignant tumors (Po0.01). This study reveals two distinct patterns of genomic imbalance in phyllodes tumors: benign, with none or a few chromosome changes and malignant, with numerous recurrent chromosomal changes, in particular 1q gain and 13q loss. Helpful additional pathological criteria for differentiating the two genetic groups of phyllodes tumors are the nuclear size and the mitotic rate. Modern Pathology (2007) 20, 435-444.

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p53 Protein Expression and Gene Mutation in Phyllodes Tumors of the Breast

Cited by 29 publications

References 21 publications

p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study

p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study

Mutational analysis of MED12 in fibroadenomas and phyllodes tumors of the breast by means of targeted next-generation sequencing

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

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