Malignant phyllodes tumours of the breast display increased stromal p53 protein expression

Millar, Ewan K.A.; Beretov, Julia; Marr, Penelope; Sarris, Maria; Clarke, Raymond A.; Jh, Kearsley; Lee, C S

doi:10.1111/j.1365-2559.1999.00666.x

Cited by 71 publications

(38 citation statements)

References 8 publications

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“…Our results support those of a previous study, which showed that Ki-67 expression correlates with the histologic classification of PT (13). Our study also is in agreement with others in that p53 protein expression correlates with the histologic classification of PT (14,15). In our study, however, neither Ki-67 nor p53 expression correlated with clinical behavior.…”

Section: Discussionsupporting

confidence: 81%

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Pathologic, Immunohistochemical, and Molecular Features of Benign and Malignant Phyllodes Tumors of the Breast

et al. 2001

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The histologic distinction between benign and malignant Phyllodes tumors (PT) is often difficult and arbitrary. We analyzed a group of benign and malignant PT to determine whether specific histologic features and expression of Ki-67 and p53 could be useful in distinguishing benign PT from malignant tumors. We also determined whether deletions in Chromosome 3p at the FHIT and hMLH1 loci are common abnormalities in PT. Twenty PT were histologically classified as benign (7) or malignant (13). Seven of the malignant PT were low grade, and six were high grade. Ki-67 and p53 immunohistochemistry was performed on all tumors and analyzed for the stromal and for the epithelial component. PCRbased loss of heterozygosity analyses were performed with the following markers on Chromosome 3p: D3S1478 (3p21.2-21.3), D3S1289 (3p21.1-21.2), and D3S1295 (3p14.3-21.1). The distribution of immunoreactivity for Ki-67 was analyzed by quantifying the percentage of positive nuclei and expressed as the labeling index (LI). Patients' ages ranged from 13 to 71 years (median: 51 y). After a mean follow-up period of 8 years, none of the PT metastasized, whereas three recurred locally. Although malignant PT were larger than benign PT (means, 7.1 versus 4.3 cm), this difference was not statistically significant. Five tumors had infiltrating margins, and 14 were circumscribed. The Ki-67 LI in low-grade malignant PT (16 ؎ 25.5) was significantly higher than that in benign PT (3.6 ؎ 4.8), whereas the LI in the high-grade malignant PT group (50 ؎ 21.9) was significantly higher than that in low-grade malignant tumors (P ‫؍‬ .012). The Ki-67 LI in the three tumors that recurred was less than 10%. Two of seven (29%) benign PT were focally positive for p53, whereas four of seven (57%) low-grade malignant and three of six (50%) highgrade malignant PT were diffusely positive for p53. The three tumors that recurred initially were histologically benign, as were two of the recurrences. One recurrent tumor evolved to a high-grade malignant PT. Margins were greater than 1 cm in all tumors except four, three of which recurred locally. No allelic loss of 3p was found. In summary, Ki-67 expression may assist in distinguishing benign from malignant PT in diagnostically difficult cases. 3p deletions do not play a significant role in the development of these tumors. Neither Ki-67 nor p53 can reliably predict recurrence. Histologically highgrade malignant PT have a favorable prognosis if widely excised. We emphasize the importance of adequate margins in the treatment of benign and malignant PT.

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Section: Discussionsupporting

confidence: 81%

“…Recent studies have suggested that Ki-67, a proliferation marker, and p53, a tumor suppressor gene, may be implicated in predicting behavior of breast carcinomas in general and of PT in particular (13)(14)(15). In addition, cytogenetic investigation has been performed in a small number of PT (16,17).…”

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confidence: 99%

Pathologic, Immunohistochemical, and Molecular Features of Benign and Malignant Phyllodes Tumors of the Breast

et al. 2001

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“…In breast phyllodes tumors, the role of p53 has been fairly well investigated, 1,[16][17][18][19] with some authors suggesting a possible prognostic function, 16,18,19 while its predictive utility has not been validated by others. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of p53 expression in phyllodes tumors have focused primarily on stromal cells, 14,[16][17][18]25 with observation of perithelial accentuation of stromal cell staining. 14, 18 Feakins et al 1 mentioned that the epithelial component in their cases usually stained negatively, while in another two reports, p53 reactivity was described in the breast epithelium in conjunction with stromal staining, 26,27 and it was postulated that dual expression of p53 protein in both the epithelium and stroma reflected the existence of an interaction between these components, 26 akin to the conclusion of Sawyer et al, 28 who believed that both epithelium and stroma of phyllodes tumors were participants in the neoplastic process. Our finding of an association between p53 stromal staining with that in luminal and myoepithelium lends credence to this purported relationship, although the presence of myoepithelial staining and its possible role in this process is unclear.…”

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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Malignant phyllodes tumours of the breast display increased stromal p53 protein expression

Cited by 71 publications

References 8 publications

Pathologic, Immunohistochemical, and Molecular Features of Benign and Malignant Phyllodes Tumors of the Breast

Pathologic, Immunohistochemical, and Molecular Features of Benign and Malignant Phyllodes Tumors of the Breast

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

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