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Aleskandarany, Mohammed A.; Green, Andrew R.; Ashankyty, I.; Elmouna, A.; Diez-Rodriguez, Maria; Nolan, Christopher C.; Ellis, Ian O.; Rakha, Emad (2016)
Publisher: Springer
Languages: English
Types: Article
In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression hot spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), co-efficient of variation, and correlation co-efficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (P\0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r = 0.98, P\0.001). In conclusion, assessment of Ki67 expression using HS scoring method on a full-face BC tissue section can represent the primary tumour growth fraction that is likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.
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    • Park D, Karesen R, Noren T, Sauer T (2007) Ki-67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications. Virchows Archiv, 451(1):11- 18.
    • Brown DC, Gatter KC: Ki67 protein: the immaculate deception? In., vol. 40; 2002: 2-11.
    • Heidebrecht HJ, Buck F, Haas K, Wacker HH, Parwaresch R (1996) Monoclonal antibodies KiS3 and Ki-S5 yield new data on the 'Ki-67' proteins. Cell Proliferation, 29(7):413-425.
    • Wu YL, Luo HY, Kanaan N, Wu JP (2000) The proteasome controls the expression of a proliferation-associated nuclear antigen Ki-67. Journal of Cellular Biochemistry, 76(4):596- 604.
    • Colozza M, Azambuja E, Cardoso F, Sotiriou C, Larsimont D, Piccart MJ: Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? In., vol. 16; 2005: 1723-1739.
    • Lehr HA, Hansen DA, Kussick S, Li M, Hwang H, Krummenauer F, Trouet S, Gown AM (1999) Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count. Hum Pathol, 30(11):1314-1320.
    • Thor AD, Liu S, Moore DH, 2nd, Edgerton SM (1999) Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol, 17(2):470-477.
    • Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, Coates AS, Collins J, Castiglione-Gertsch M, Gusterson BA (2003) Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors--a surrogate marker? Cancer, 97(5):1321-1331.
    • Domagala W, Markiewski M, Harezga B, Dukowicz A, Osborn M (1996) Prognostic significance of tumor cell proliferation rate as determined by the MIB-1 antibody in breast carcinoma: its relationship with vimentin and p53 protein. Clin Cancer Res, 2(1):147-154.
    • de Azambuja E, Cardoso F, de Castro G, Jr., Colozza M, Mano MS, Durbecq V, Sotiriou C, Larsimont D, Piccart-Gebhart MJ, Paesmans M (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer, 96(10):1504-1513.
    • Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell'Orto P, Maiorano E, MacGrogan G, Braye SG, Ohlschlegel C et al (2008) Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrineresponsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol, 26(34):5569-5575.
    • Aleskandarany MA, Green AR, Rakha EA, Mohammed RA, Elsheikh SE, Powe DG, Paish EC, Macmillan RD, Chan S, Ahmed SI et al (2009) Growth fraction as a predictor of response to chemotherapy in node negative breast cancer. Int J Cancer.
    • Brown JR, DiGiovanna MP, Killelea B, Lannin DR, Rimm DL (2014) Quantitative assessment Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer. Lab Invest, 94(1):98-106.
    • Ingolf J-B, Russalina M, Simona M, Julia R, Gilda S, Bohle RM, Andrea H, Erich S, Daniel H (2014) Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy? BioMed Research International, 2014:628217.
    • Takei H, Kurosumi M, Yoshida T, Hayashi Y, Higuchi T, Uchida S, Ninomiya J, Oba H, Inoue K, Nagai S et al (2011) Neoadjuvant endocrine therapy of breast cancer: which patients would benefit and what are the advantages? Breast cancer (Tokyo, Japan), 18(2):85-91.
    • von Minckwitz G, Schmitt WD, Loibl S, Muller BM, Blohmer JU, Sinn BV, Eidtmann H, Eiermann W, Gerber B, Tesch H et al (2013) Ki67 measured after neoadjuvant chemotherapy for primary breast cancer. Clin Cancer Res, 19(16):4521-4531.
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