Abstract
Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.
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References
Tan PH, Tse G, Lee A et al (2012) Fibroepithelial tumours. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ (eds) WHO classification of tumours of the breast, 4th edn. Int Agency Res Cancer, Lyon, pp. 142–147
Parker SJ, Harries SA (2001) Phyllodes tumours. Postgrad Med J 77:428–435
Tan PH, Thike AA, Tan WJ et al (2012) Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol 65:69–76
Schwartz T, Stark A, Pang J et al (2013) Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women. Cancer 119:488–494
Kim YS, Jung MJ, Ryu DW, Lee CH (2014) Clinicopathologic characteristics of breast cancer stem cells identified on the basis of aldehyde dehydrogenase 1 expression. J Breast Cancer 17:121–128
Lin J, Huang C, Yu J et al (2014) Malignant phyllodes tumours display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumour stem cells. Breast Cancer Res 16:R29
Sawyer EJ, Poulsom R, Hunt FT et al (2003) Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit. J Pathol 200:59–64
Tse GM, Putti TC, Lui PC et al (2004) Increased c-kit (CD117) expression in malignant mammary phyllodes tumours. Mod Pathol 17:827–831
Carvalho S, e Silva AO, Milanezi F et al (2004) C-kit and PDGFRA in breast phyllodes tumours: overexpression without mutations? J Clin Pathol 57:1075–1079
Tan PH, Jayabaskar T, Yip G et al (2005) P53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumours: a tissue microarray study. Mod Pathol 18:1527–1534
Yonemori K, Hasegawa T, Shimizu C et al (2006) Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumours of the breast. Pathol Res Pract 202:705–712
Djordjevic B, Hanna WM (2008) Expression of c-kit in fibroepithelial lesions of the breast is a mast cell phenomenon. Mod Pathol 21:1238–1245
Bose P, Dunn S, Yang J, Allen R, El-khoury C, Tfayli A (2010) c-Kit expression and mutations in phyllodes tumours of the breast. Anticancer Res 30:4731–4736
Noronha Y, Raza A, Hutchins B et al (2011) CD34, CD117, and Ki-67 expression in phyllodes tumour of the breast: an immunohistochemical study of 33 cases. Int J Surg Pathol 19:152–158
Tan WJ, Thike AA, Tan SY et al (2015) CD117 expression in breast phyllodes tumours correlates with adverse pathologic parameters and reduced survival. Mod Pathol 28:352–358
Tawasil J, Go EM, Tsang JY, Ni YB, Ko CW, Tse GM (2015) Associations of epithelial c-kit expression in phyllodes tumours of the breast. J Clin Pathol 68:808–811
Chougule A, Bal A, Rastogi P, Das A (2015) Recurrent phyllodes tumour in the male breast in a background of gynaecomastia. Breast Dis 35:139–142
Liu J, Liu X, Feng X, Lv S, Zhang W, Niu Y (2015) C-kit overexpression correlates with KIT gene copy numbers increases in phyllodes tumours of the breast. Breast Cancer Res Treat 149:395–401
Chatterjee D, Bal A, Das A, Singh G (2015) Proliferation rate and breast cancer subtype, but not ALDH1 expression, predict pathological response to neoadjuvant chemotherapy in locally advanced breast cancer. Virchows Arch 467:303–310
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This study is done on archival paraffin blocks, and no additional procedures were performed on the patients to obtain tissues. Informed written consent was taken from patients before surgery.
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Chougule, A., Bal, A., Das, A. et al. In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features. Virchows Arch 469, 651–658 (2016). https://doi.org/10.1007/s00428-016-2023-9
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DOI: https://doi.org/10.1007/s00428-016-2023-9