Immunohistochemical Expression of Ki-67 and p53 in Different Grades of Phyllodes Tumors of the Breast and its Association with Clinicopathological Characteristics

Main Article Content

Sana Tahir
Dr. Lubna Avesi
Dr.Farheen Danish
Dr.Saba Hassan Shamim
Professor Uzma Bukhari
Dr.Farah Muhammad Ali

Abstract

Objective:This study aimed to investigate the immunoreactivity of Ki67 and p53 in Phyllodes tumors (PTs) of the breast and assess their correlation with clinicopathological features, including PT grade and clinical parameters.


Methodology: A comparative, analytical cross-sectional design was employed to evaluate Ki67 and p53 immunoreactivity in the Phyllodes tumors. The research was conducted at the Histopathology Department, DDRRL/DUHS, Karachi, over
an 8-month period. Ethical approval was also obtained from DUHS's board. Purposive nonprobability sampling was used to select the patients. Immunohistochemistry, performed on FFPE tissue blocks, involved evaluating Ki67 and p53 staining. Statistical analysis (descriptive, chi-squared, and Kruskal Wallis tests) was carried out using IBM SPSS version 26, and a p-value <0.05 was considered statistically significant.


Results:The research involved   50 patients, comprising benign 19 (38%), borderline 23 (46%), and malignant 08 (16%) PTs. Malignant tumors exhibited significantly higher expression of Ki67 and p53 compared to benign and borderline tumors (p < 0.005). Clinicopathological parameters, such as tumor mobility, skin ulceration, tumor borders, leaf-like architecture, stromal overgrowth, necrosis, and surgical margins, showed significant associations with Ki67 and p53 expression (p < 0.005). These results recommend that Ki67 and p53 may serve as valuable diagnostic and prognostic markers in PTs.


Conclusion: The study's results indicate that the immunohistochemical evaluation of Ki67 and p53 could be beneficial in the diagnosis of PTs. The association between Ki67 and p53 expression and various clinicopathological features, particularly PT grade, highlights their potential clinical significance. Further research could contribute to the advancement of standardized diagnostic and prognostic criteria for PTs, improving patient management and outcomes.

Article Details

How to Cite
1.
Tahir S, Avesi DL, Danish D, Hassan Shamim D, Bukhari PU, Muhammad Ali D. Immunohistochemical Expression of Ki-67 and p53 in Different Grades of Phyllodes Tumors of the Breast and its Association with Clinicopathological Characteristics. J Postgrad Med Inst [Internet]. 2024 Oct. 14 [cited 2024 Oct. 16];38(3). Available from: https://jpmi.org.pk/index.php/jpmi/article/view/3380
Section
Original Article
Author Biographies

Sana Tahir, Dow University of Health Sciences (DUHS), Karachi, Pakistan

FCPS Resident

Dr. Lubna Avesi, Dow University of Health Sciences (DUHS), Karachi, Pakistan

Associate professor 

Dr.Farheen Danish, Dow University of Health Sciences (DUHS), Karachi, Pakistan

Assistant professor

Dr.Saba Hassan Shamim, Dow University of Health Sciences (DUHS), Karachi, Pakistan

Associate professor

Professor Uzma Bukhari, Dow University of Health Sciences (DUHS), Karachi, Pakistan

professor

Dr.Farah Muhammad Ali, Dow University of Health Sciences (DUHS), Karachi, Pakistan

resident

References

Lissidini G, Mulè A, Santoro A, Papa G, Nicosia L, Cassano E, et al. Malignant phyllodes tumor of the breast: a systematic review. Pathologica. 2022;114(2):111.

Perea IN, Embry AH, Cros NE, Trusso WN, Martin LS, Llach AC. Practica Clinica. Obstet Ginecol. 2019;62(2):163-7.

Moffat C, Pinder S, Dixon A, Elston C, Blamey R, Ellis I. Phyllodes tumours of the breast: a clinicopathological review of thirty-two cases. Histopathology. 1995;27(3):205-18.

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 Journal of Surgical Oncology. 2015;13:1-4.

WHOCoTE B. International Agency for Research on C. World Health O WHO classification of tumours Breast Tumours Lyon: International Agency for Research on Cancer. 2019.

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.

Teo JY, Cheong CSJ, Wong CY. Low local recurrence rates in young Asian patients with phyllodes tumours: less is more. ANZ Journal of Surgery. 2012;82(5):325-8.

Tan BY, Fox SB, Lakhani SR, Tan PH. Survey of recurrent diagnostic challenges in breast phyllodes tumours. Histopathology. 2023;82(1):95-105.

Rosa M, Agosto-Arroyo E. Core needle biopsy of benign, borderline and in-situ problematic lesions of the breast: Diagnosis, differential diagnosis and immunohistochemistry. Annals of diagnostic pathology. 2019;43:151407.

Rakha E, Mihai R, Abbas A, Bennett R, Campora M, Morena P, et al. Diagnostic concordance of phyllodes tumour of the breast. Histopathology. 2021;79(4):607-18.

Roknsharifi S, Wattamwar K, Fishman MD, Ward RC, Ford K, Faintuch S, et al. Image-guided microinvasive percutaneous treatment of breast lesions: where do we stand? Radiographics. 2021;41(4):945-66.

Ali NAM, Nasaruddin AF, Mohamed SS, Rahman WFW. Ki67 and P53 expression in relation to clinicopathological features in phyllodes tumour of the breast. Asian Pacific journal of cancer prevention: APJCP. 2020;21(9):2653.

Bogach J, Shakeel S, Wright FC, Hong NJL. Phyllodes tumors: a scoping review of the literature. Annals of Surgical Oncology. 2022;29:446-59.

Shubham S, Ahuja A, Bhardwaj M. Immunohistochemical expression of Ki-67, p53, and CD10 in phyllodes tumor and their correlation with its histological grade. Journal of Laboratory Physicians. 2019;11(04):330-4.

Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer. Molecular medicine reports. 2015;11(3):1566-72.

Tse GM, Niu Y, Shi H-J. Phyllodes tumor of the breast: an update. Breast cancer. 2010;17:29-34.

Zhang Y, Kleer CG. Phyllodes tumor of the breast: histopathologic features, differential diagnosis, and molecular/genetic updates. Archives of pathology & laboratory medicine. 2016;140(7):665-71.

Lokuhetty D, White VA, Watanabe R, Cree IA. Breast Tumours: International Agency for Research on Cancer; 2019.

Lakhani S, Ellis I, Schnitt S, Tan P, van de Vijver M. World Health Organization classification of tumours, volume 2: breast tumours. Lyon, France, IARC Press; 2019.

Nielsen TO, Leung SCY, Rimm DL, Dodson A, Acs B, Badve S, et al. Assessment of Ki67 in breast cancer: updated recommendations from the international Ki67 in breast cancer working group. JNCI: Journal of the National Cancer Institute. 2021;113(7):808-19.

Yonemori K, Hasegawa T, Shimizu C, Shibata T, Matsumoto K, Kouno T, et al. Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast. Pathology-Research and Practice. 2006;202(10):705-12.

Rivero L, Graudenz M, Aschton-Prolla P, Delgado A, Kliemann L. Accuracy of p53 and ki-67 in the graduation of phyllodes tumor, a model for practical application. Surgical and Experimental Pathology. 2020;3:1-8.

Fede ABdS, Pereira Souza R, Doi M, De Brot M, Aparecida Bueno de Toledo Osorio C, Rocha Melo Gondim G, et al. Malignant phyllodes tumor of the breast: a practice review. Clinics and Practice. 2021;11(2):205-15.

Alkushi A, Arabi H, Al-Riyees L, Aldakheel AM, Al Zarah R, Alhussein F, et al. Phyllodes tumor of the breast clinical experience and outcomes: A retrospective cohort tertiary hospital experience. Annals of Diagnostic Pathology. 2021;51:151702.

Atalay C, Kinas V, Celebioglu S. Analysis of patients with phyllodes tumor of the breast. Turkish Journal of Surgery/Ulusal cerrahi dergisi. 2014;30(3):129.

Cabioglu N, Celik T, Ozmen V, Igci A, Muslumanoglu M, Ozcinar B. Treatment methods in phyllodes tumors of the breast. J Breast Health. 2008;4:99-104.

Tummidi S, Kothari K, Agnihotri M, Naik L, Sood P. Fibroadenoma versus phyllodes tumor: a vexing problem revisited! BMC cancer. 2020;20:1-12.

Hashmi AA, Mallick BA, Rashid K, Zafar S, Zia S, Malik UA, et al. Clinicopathological Parameters Predicting Malignancy in Phyllodes Tumor of the Breast. Cureus. 2023;15(9).

Yabanoglu H, Colakoglu T, Aytac H, Parlakgumus A, Bolat F, Pourbagher A, Yildirim S. Comparison of predictive factors for the diagnosis and clinical course of phyllodes tumours of the breast. Acta Chirurgica Belgica. 2015;115(1):27-32.

Di Liso E, Bottosso M, Mele ML, Tsvetkova V, Dieci MV, Miglietta F, et al. Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases. ESMO open. 2020;5(5):e000843.

Adam M-J, Bendifallah S, Kalhorpour N, Cohen-Steiner C, Ropars L, Mahmood A, et al. Time to revise classification of phyllodes tumors of breast? Results of a French multicentric study. European Journal of Surgical Oncology. 2018;44(11):1743-9.

Chao TC, Lo YF, Chen SC, Chen MF. Sonographic features of phyllodes tumors of the breast. Ultrasound in Obstetrics and Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002;20(1):64-71.

Zhang L, Yang C, Pfeifer JD, Caprioli RM, Judd AM, Patterson NH, et al. Histopathologic, immunophenotypic, and proteomics characteristics of low-grade phyllodes tumor and fibroadenoma: more similarities than differences. NPJ breast cancer. 2020;6(1):27.

Kucuk U, Bayol U, Pala EE, Cumurcu S. Importance of P53, Ki-67 expression in the differential diagnosis of benign/malignant phyllodes tumors of the breast. Indian Journal of Pathology and Microbiology. 2013;56(2):129.

Pednekar J, Khan N, Pillai S, Singhal P, Pillai R, Kumar M. Diagnosis and management of phyllodes tumour of the breast-5 year study of a tertiary care centre. International Journal of Surgery and Medicine. 2021;7(5):28-.

Yuan M, Saeki H, Horimoto Y, Ishizuka Y, Onagi H, Saito M, et al. Stromal Ki67 Expression Might be a Useful Marker for Distinguishing Fibroadenoma From Benign Phyllodes Tumor of the Breast. International Journal of Surgical Pathology. 2023:10668969231171132.

Gary M, Lui PC, Scolyer RA, Putti TC, Kung FY, Law BK, et al. Tumour angiogenesis and p53 protein expression in mammary phyllodes tumors. Modern pathology. 2003;16(10):1007-13.

Fernández-Ferreira R, Arroyave-Ramírez A, Motola-Kuba D, Alvarado-Luna G, Mackinney-Novelo I, Segura-Rivera R. Giant benign mammary phyllodes tumor: report of a case and review of the literature. Case Reports in Oncology. 2021;14(1):123-33.

Zhang T, Feng L, Lian J, Ren W-L. Giant benign phyllodes breast tumour with pulmonary nodule mimicking malignancy: A case report. World Journal of Clinical Cases. 2020;8(16):3591.