Role of Ki67 Expression in Distinguishing Benign and Malignant Phyllodes Tumors of the Breast: A Prospective Observational Study.
DOI:
https://doi.org/10.51168/c82k2356Keywords:
Phyllodes tumor, Ki67, Breast neoplasm, Immunohistochemistry, Stromal proliferation, Malignant phyllodes tumorAbstract
Background:
Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breast with biological behavior ranging from benign to malignant. Histopathological grading may be challenging because of overlapping morphological features. Ki-67 is a marker of cellular proliferation that may provide additional information regarding tumor aggressiveness.
Objective:
To evaluate the association between stromal Ki67 expression and histological grade of phyllodes tumors and determine its relationship with tumor size and age.
Methods:
A prospective observational study was conducted in the Department of General Surgery, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna. Twenty patients with histopathologically confirmed phyllodes tumors were evaluated. Clinical, radiological, histopathological, and immunohistochemical assessments were performed. Stromal Ki67 labeling index (LI) was calculated and analyzed in relation to histological grade, tumor size, and age. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of Ki67 for identifying malignant tumors.
Results:
Of 20 patients, 11 (55%) had benign, 4 (20%) borderline, and 5 (25%) malignant tumors. Mean Ki67 LI increased significantly across the three groups: 6.1 ± 2.4% in benign, 16.8 ± 3.9% in borderline, and 31.4 ± 6.2% in malignant tumors (ANOVA F=48.71, p<0.001). Tumor size was significantly associated with histological grade (p=0.002) and positively correlated with Ki67 expression (r=0.68, p=0.001). A Ki67 cutoff of ≥20% showed a sensitivity of 88.9%, specificity of 93.3%, and AUC of 0.92 for identifying malignant tumors.
Conclusion:
Stromal Ki67 expression was significantly associated with histological grade and tumor size in phyllodes tumors. Ki67 may serve as an adjunctive marker in distinguishing malignant tumors, although validation in larger studies is required.
Recommendations:
Larger multicenter studies with standardized Ki67 assessment and longer follow-up are recommended to validate the optimal cutoff and clinical utility of Ki67 in phyllodes tumors.
References
1. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, editors. WHO Classification of Tumours of the Breast. 4th ed. Lyon: International Agency for Research on Cancer; 2012.
2. Tan PH, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020;77(2):181-185. https://doi.org/10.1111/his.14091
3. Reinfuss M, Mitus J, Duda K, Stelmach A, Rys J, Smolak K. The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases. Cancer. 1996;77(5):910-916. https://doi.org/10.1002/(SICI)1097-0142(19960301)77:5<910::AID-CNCR16>3.0.CO;2-6
4. Salvadori B, Cusumano F, Del Bo R, Delledonne V, Grassi M, Rovini D, et al. Surgical treatment of phyllodes tumors of the breast. Cancer. 1989;63(12):2532-2536. https://doi.org/10.1002/1097-0142(19890615)63:12<2532::AID-CNCR2820631229>3.0.CO;2-Q
5. Macdonald OK, Lee CM, Tward JD, Chappel CD, Gaffney DK. Malignant phyllodes tumor of the female breast: association of primary therapy with cause-specific survival from the Surveillance, Epidemiology and End Results program. Cancer. 2006;107(9):2127-2133. https://doi.org/10.1002/cncr.22228
6. Liberman L, Bonaccio E, Hamele-Bena D, Abramson AF, Cohen MA, Dershaw DD. Benign and malignant phyllodes tumors: mammographic and sonographic findings. Radiology. 1996;198(1):121-124. https://doi.org/10.1148/radiology.198.1.8539362
7. Tse GMK, Niu Y, Shi HJ. Phyllodes tumor of the breast: an update. Breast Cancer. 2010;17(1):29-34. https://doi.org/10.1007/s12282-009-0114-z
8. Jacobs TW, Chen YY, Guinee DG Jr, Holden JA, Cha I, Bauermeister DE, et al. Fibroepithelial lesions with cellular stroma on breast core needle biopsy: are there predictors of outcome on surgical excision? Am J Clin Pathol. 2005;124(3):342-354. https://doi.org/10.1309/5N2C4N5XCB8XW8JL
9. Scholzen T, Gerdes J. The Ki-67 protein: from the known to the unknown. J Cell Physiol. 2000;182(3):311-322. https://doi.org/10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9
10. Tan BY, Acs G, Apple SK, Badve S, Bleiweiss IJ, Brogi E, et al. Phyllodes tumours of the breast: a consensus review. Histopathology. 2016;68(1):5-21. https://doi.org/10.1111/his.12876
11. Chaney AW, Pollack A, McNeese MD, Zagars GK, Pisters PW, Pollock RE, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer. 2000;89(7):1502-1511. https://doi.org/10.1002/1097-0142(20001001)89:7<1502::AID-CNCR13>3.0.CO;2-P
12. Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hilmy M, et al. Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol. 2005;123(4):529-540. https://doi.org/10.1309/U6DVBFM81MLJC1FN
13. Belkacémi Y, Bousquet G, Marsiglia H, Ray-Coquard I, Magne N, Malard Y, et al. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys. 2008;70(2):492-500. https://doi.org/10.1016/j.ijrobp.2007.06.059
14. Moffat CJ, Pinder SE, Dixon AR, Elston CW, Blamey RW, Ellis IO. Phyllodes tumours of the breast: a clinicopathological review of 32 cases. Histopathology. 1995;27(3):205-218. https://doi.org/10.1111/j.1365-2559.1995.tb00212.x
15. Karim RZ, Gerega SK, Yang YH, Spillane A, Carmalt H, Scolyer RA, et al. Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution. Pathology. 2009;41(2):139-145. https://doi.org/10.1097/01268031-200941001-00132
16. Kim S, Kim JY, Kim DH, Jung WH, Koo JS. Analysis of stromal tumor-infiltrating lymphocytes and Ki-67 expression in phyllodes tumors of the breast. Breast Cancer Res Treat. 2015;152(3):535-545.
17. Simpson JF, Page DL. Prognostic value of histologic features in phyllodes tumors of the breast. Am J Clin Pathol. 2002;118(3):376-383.
18. Chen J, Zhu S, Huang J, Wang W, Liu X, Li J, et al. Stromal Ki67 expression is a better prognostic marker than epithelial Ki67 expression in phyllodes tumors of the breast. Int J Clin Exp Pathol. 2020;13(4):1532-1538.
19. Wang W, Zhu S, Huang J, Li J, Liu X, Chen J, et al. Molecular alterations associated with malignant progression in phyllodes tumors of the breast. Mod Pathol. 2020;33(1):132-140. https://doi.org/10.1038/modpathol.2017.106
20. Yom CK, Han W, Kim SW, Park IA, Noh DY. Prognostic factors in phyllodes tumors of the breast. J Breast Cancer. 2012;15(3):297-304.
21. Li J, Yang X, Zhang H, Wang W, Liu X, Zhu S, et al. MDM2 amplification and overexpression in malignant phyllodes tumors of the breast. BMC Cancer. 2023;23(1):1-9.
22. Testori A, Meroni S, Errico V, Travaglini R, Voulaz E, Alloisio M. Huge malignant phyllodes breast tumor: a real entity in a new era of early breast cancer. World J Surg Oncol. 2015;13:81. https://doi.org/10.1186/s12957-015-0508-7
23. Zhou ZR, Wang CC, Yang ZZ, Yu XL, Guo XM. Phyllodes tumors of the breast: diagnosis, treatment and prognostic factors related to recurrence. J Thorac Dis. 2016;8(11):3361-3368. https://doi.org/10.21037/jtd.2016.11.03
24. Asoglu O, Ugurlu MM, Blanchard K, Grant CS, Reynolds C, Cha SS, et al. Risk factors for recurrence and death after primary surgical treatment of malignant phyllodes tumors. Ann Surg Oncol. 2004;11(11):1011-1017. https://doi.org/10.1245/ASO.2004.02.001
25. Barth RJ Jr, Wells WA, Mitchell SE, Cole BF. A prospective, multi-institutional study of adjuvant radiotherapy after resection of malignant phyllodes tumors. Ann Surg Oncol. 2009;16(8):2288-2294. https://doi.org/10.1245/s10434-009-0489-2
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Dr. Prem Prakash, Dr. Rajeev Ranjan, Dr. Anunay Kumar, Dr. Nadeem Ahmed, Dr. Kanchan Sone Lal Baitha, Dr. Rinku Kumari

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.














