CD34,CD117,and Ki-67 Expression in Phyllodes Tumor of the Breast: An Immunohistochemical Study of 33 Cases

Abstract

Phyllodes tumors (PTs) of the breast are biphasic lesions, comprising an epithelial component set within a neoplastic spindle-celled stroma. These tumors have been classified as benign, borderline, and malignant based on a combination of histological criteria, including stromal cellularity, nuclear pleomorphism, mitotic rate, stromal overgrowth, and margin appearance. The aim of this study was to evaluate the expression of CD34, CD117 (c-kit), and Ki-67 in PT of the breast and attempt to correlate the staining pattern with tumor grade by morphology. Immunohistochemical expression of CD117, CD34, and Ki-67 was studied on formalin-fixed, paraffin-embedded archival tissue material from 33 cases of PT. Histologically, there were 21 benign, 6 borderline, and 6 malignant (high-grade) tumors. All 6 histologically malignant PTs were positive for CD117 (100%), but only 1 marked with CD34 (16.7%). Borderline PTs frequently coexpressed CD34 and CD117 (66.7%). The benign PTs, on the other hand, most commonly (52.4%) showed a CD34(+)/CD117(-) immunoprofile with 33.3% cases coexpressing the markers: that is, CD34(+)/CD117(+). Although most benign PTs (80.6%) showed a Ki-67 of <2%, a few cases showed slightly higher proliferation indices. This study indicates that CD34 and CD117 are differentially expressed in benign and malignant PTs. These markers, therefore, in combination, may be used as an adjunct to morphology in the subclassification of PTs.

Keywords

phyllodes tumor CD34 CD117 Ki-67

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References

Azzopardi JG Sarcoma of the breast. In: Bennington J, ed. Problems in Breast Pathology, Major Problems in Pathology. Vol 2. Philadelphia, PA: W B Saunders. 1979: 355-359.

Kario K. , Meada S. , Mizuno Y. , et al. Phyllodes tumor of the breast: a clinicopathologic study of 34 cases. J Surg Oncol. 1990;45:46-51.

Bellocq JP , Magro G. Fibroepithelial tumors. In: Tavassoli FA , Devilee P , eds. World Health Organization Classification of Tumors: Tumors of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003:99-103.

Muller J. Ueber den feinern Bau und die Formen der krankhaften Geschwuelste. Berlin, Germany: Reimer; 1838.

Rosen PP Fibroepithelial neoplasms. In: Rosen PP , ed. Rosen’s Breast Pathology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:163-200.

Lemonaco F. Il tumore filloide della mammella (cistosarcoma filloide di J Muller). Tumori. 1960;46:156-184.

Treves N. , Sunderland DA Cystosarcoma phyllodes of the breast: a malignant and a benign tumor. Cancer. 1951;4: 1286-1332.

Moffat CJ , Pinders SE , Dixon AR , et al. Phyllodes tumors of the breast: a clinicopathological review of thirty-two cases. Histopathology. 1995;27:205-218.

Barth RJ Jr. Histologic features predict local recurrence after breast conserving treatment of phyllodes tumor. Breast Cancer Res Treat. 1999;57:291-295.

10.

Khan SA , Badve S. Phyllodes tumors of the breast. Curr Treat Options Oncol. 2001;2:139-147.

11.

Tan PH , Jayabaskar T. , Chuah KL , et al. Phyllodes tumors of the breast: the role of pathologic parameters . Am J Clin Pathol. 2005;23:529-540.

12.

Chen CM , Chen CJ , Chang CL , et al. CD34, CD117, and actin expression in phyllodes tumor of the breast. J Surg Res. 2000;94:84-91.

13.

Sawyer EJ , Poulsom R. , Hunt FT , et al. Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit. J Pathol. 2003;200:59-64.

14.

Tse GM , Putti TC , Lui PC , et al. Increased c-kit (CD117) expression in malignant mammary phyllodes tumors. Mod Pathol. 2004;17:827-831.

15.

Carvalho S. , e Silva AO , Milanezi F. , et al. c-Kit and PDG-FRA in breast phyllodes tumors: overexpression without mutations? J Clin Pathol. 2004;57:1075-1079.

16.

Tan PH , Jayabaskar T. , Yip G. , et al. p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study. Mod Pathol. 2005; 18:1527-1534.

17.

Esposito NN , Mohan D. , Brufsky A. , et al. Phyllodes tumor: a clinicopathologic and immunohistochemical study of 30 cases. Arch Pathol Lab Med. 2006;130:1516-1521.

18.

Silverman JS , Tamsen A. Mammary fibroadenoma and some phyllodes tumor stroma are composed of CD34+ fibroblasts and factor XIII a+ dendrophages. Histopathology. 1996;29:411-419.

19.

Kleer CG , Giordano TJ , Braun T. , et al. Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast. Mod Pathol. 2001;14:185-190.

20.

Niezabitowski A. , Lackowska B. , Rys J. , et al. Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: immunohistochemical and flow cytometric study of 118 cases. Breast Cancer Res Treat. 2001;65:77-85.

21.

Dacic S. , Kounelis S. , Kouri E. , et al. Immunohistochemical profile of cystosarcoma phyllodes of the breast: a study of 23 cases. Breast J. 2002 ;8:376-381.

22.

Erhan Y. , Zekioglu O. , Ersoy O. , et al. p53 and Ki-67 expression as prognostic factors in cystosarcoma phyllodes. Breast J. 2002;8:38-44.

23.

Shpitz B. , Bomstein Y. , Sternberg A. , et al. Immunoreactivity of p53, Ki-67, and c-erbB-2 in phyllodes tumors of the breast in correlation with clinical and morphologic features. J Surg Oncol. 2002;79:86-92.

24.

Chan YJ , Chen BF , Chang CL , et al. Expression of p53 protein and Ki-67 antigen in phyllodes tumor of the breast. J Chin Med Assoc. 2004;67:3-8.

25.

Yonemori K. , Hasegawa T. , Shimizu C. , et al. Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast. Pathol Res Pract. 2006;202:705-712.

26.

Lanza F. , Healy L. , Sutherland DR Structural and functional features of the CD34 antigen: an update. J Biol Regul Homeost Agents. 2001;15:1-13.

27.

Brown DC , Gatter KC Monoclonal antibody Ki-67: its use in histopathology. Histopathology . 1990;17:489-503.