Increased p53 Protein Expression in Malignant Mammary Phyllodes Tumors

Abstract

The authors reviewed 143 cases (87 benign, 37 borderline, and 19 malignant) of mammary phyllodes tumors (PTs) and used immunohistochemistry to detect p53 protein product semi-quantitatively as negative, weak, moderate and strong (scored 0 to 3). For all PTs, an increasing trend of tumor size and malignancy was detected with increasing age. For p53 staining, 60 cases (42%) were negative, 55 (38%) stained weakly, 28 (13%) stained moderately, and 10 (7%) stained strongly. Of the 87 benign PTs, 41 (47%) were negative, 37 (43%) stained weakly, and 9 (10%) stained moderately. For the 37 borderline PTs, 16 (43%) were negative, 14 (38%) stained weakly, 6 (16%) stained moderately, and 1 (3%) stained strongly. Of the 19 malignant PTs, 3 (16%) were negative, 4 (21%) stained weakly, 3 (16%) stained moderately, and 9 (47%) stained strongly. The mean intensity score for p53 staining increased progressively from benign to borderline to malignant PT, with established statistical significance (P < .0001). This is significantly correlated with mitotic count but not stromal cellularity, pleomorphism, margin, and stromal overgrowth. When considering strong staining alone (score, 3), 47% of malignant, 3% of borderline, and none of the benign PTs were positive. The use of strong positive staining for diagnosing malignant PT gave positive and negative predictive values, specificity, and sensitivity of 90%, 92.5%, 99%, and 47%, respectively. Thus diffuse strong p53 protein staining can be used as a soft sign in assisting the diagnosis of malignant PT. Conversely, negative or weak staining of p53 protein in PT is of little discriminatory value. The role of p53 gene mutation in the malignant transformation of PT is unclear; but this may not be the sole mechanism as many malignant PT were p53 protein negative.

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

“…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. 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.…”

“…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.…”

“…Interestingly, p53 immunohistochemical positivity was also noted in a proportion of luminal epithelial and myoepithelial cells in our series. 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.…”

“…1,[16][17][18][19] p53 expression has been described as being associated with malignant histological features, but does not appear to predict recurrent likelihood. 1,17 Recently, c-kit (CD117) expression was also observed in malignant phyllodes tumors, although its impact on recurrence was not addressed. 20,21 In this study, we employed p53 and CD117 immunohistochemistry on our previously described phyllodes tumors using the tissue microarray technique, and correlate the results with histological parameters and clinical outcome.…”

Increased c-kit (CD117) expression in malignant mammary phyllodes tumors

“…Parameters (1) and (2) were graded as low/mild, moderate or severe; stromal overgrowth was graded as present or absent; and the mitotic count was expressed as the number of mitotic figures per 10 high-power fields ( Â 400, Nikon Labophot, field area 0.19 mm 2 ). As previously described, 12 a diagnosis of benign phyllodes tumor was made when there was low cellularity, no stromal overgrowth, mild pleomorphism, a rounded margin and a mitotic count of 2 or less per 10 highpower fields. Malignant phyllodes tumor was diagnosed when the mitotic count was 5 or more per 10 high-power fields together with stromal overgrowth and an infiltrative margin.…”