Accuracy of p53 and ki-67 in the graduation of phyllodes tumor, a model for practical application

Abstract

Abstract Background The accurate graduation of a phyllodes tumor (PT) is critical for effective treatment as it allows correct surgical management, and avoids inadequate excision for malignant or borderline PT, or surgical overtreatment in benign PT. PTs of the breast are notoriously difficult to classify, and reliable differentiation of a benign PT from a borderline or malignant PT can be problematic, especially among relatively inexperienced pathologists. Although several authors acknowledge a strong relationship between the immunohistochemical expression of p53 and Ki-67 and the histopathological grade of PT—with potential impact on diagnostic accuracy—the literature lacks consensus about which cutoff defines a positive index test. The objective of this study is to establish a practical application score that increases the graduation accuracy of PT through the appropriate use of these auxiliary methods. Methods A retrospective study cohort of 146 pathology reviewed PTs surgically removed between January 2000 and December 2015. The Ki-67 test was considered positive if > 10% of neoplastic cells showed nuclear staining. The p53 test was considered positive if > 10% of neoplastic nuclear cells showed nuclear staining in a moderate or strong intensity. Results Of the 146 PT cases reviewed, 110 were classified as benign, 16 as borderline, and 20 as malignant. The correlation between age and size with benign, borderline, and malignant subgroups was statistically significant (p < 0.001). Significance was observed in the expression of both Ki-67 and p53 in the comparison of benign, borderline, and malignant PT with p < 0.001 and a 95% confidence interval (CI). When correlating the presence of positivity in either of the two index tests with the diagnosis of borderline or malignant PT, we reached a sensitivity of 100% and a specificity of 91.8 (p < 0.001; 95% CI). Conclusion We propose a practical methodology to achieve an accurate grade of PT, based on clearly defined and easy to apply cutoffs of a simple immunohistochemical panel of Ki-67 and p53. A PT positive for either of the index tests should be graded as borderline or malignant, so pathologists can use this test to improve accuracy. We hope this new approach might provide the basis for the development of standardization in using p53 and Ki-67 for grading PT.