ORIGINAL ARTICLE
High Ki-67 expression is a marker of poor survival in apocrine breast carcinoma
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1
Department of Tumor Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Poland
2
Institute of Medical Sciences, Medical College of Rzeszow University, Rzeszow, Poland
3
Department Laboratory of Molecular Diagnostics, Cytogenetics and Flow Cytometry Specialist Hospital in Brzozow, Poland
Submission date: 2019-06-01
Acceptance date: 2019-12-30
Publication date: 2020-07-21
Pol J Pathol 2020;71(2):107-119
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ABSTRACT
Apocrine carcinoma is a very rare type of breast cancer, which represents 0.5-4% of all breast cancers. The aim of the study was to analyze biological and clinical features of apocrine carcinoma and their influence on patients survival.
The studied group consists of 57 patients, who underwent treatment between 1987 and 2010. Expression of ER, PgR, HER2, AR, GCDFP-15, EGFR, CK 5/6, CK 8/18 and Ki-67 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. Presence of emboli and extent of lymphocyte infiltration were assessed on haematoxylin-eosin-stained slides.
In the investigated group, 16 cases were ER/PgR positive and 49 were AR-positive. ER/PgR-negative tumours were often characterised by CK5/6 and EGFR positivity. The presence of AR was related to HER-2 and GCDFP-15 expression and tumours with expression of CK5/6 were more likely be EGFR positive and had higher Ki-67 LI. Higher probability of 10-years OS and DFS was observed in patients with tumours characterized by Ki-67 LI < 20% (p = 0.036 and p = 0.009, respectively). Favourable trend in OS was noted for patients with smaller tumours (p = 0.053), without lymph node metastases (p = 0.074) and without EGFR expression (p = 0.060).
In apocrine breast carcinoma expression of Ki-67 is one of the most important factors influencing patients’ survival.
REFERENCES (36)
1.
Celis JE, Gromova I, Gromov P, et al. Molecular pathology of breast apocrine carcinomas: a protein expression signature specific for benign apocrine metaplasia. FEBS Lett 2006; 580: 2935-2944.
2.
Makki J. Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance. Clin Med Insights Pathol 2015; 8: 23-31.
3.
O’Malley FP, Bane A. An update on apocrine lesions of the breast. Histopathology 2008; 52: 3-10.
4.
Honma N, Takubo K, Akiyama F, et al. Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast. Histopathology 2005; 47: 195-201.
5.
Masood S, Rosa M. The challenge of apocrine proliferations of the breast: a morphologic approach. Pathol Res Pract 2009; 205: 155-164.
6.
Farmer P, Bonnefoi H, Becette V, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 2005; 24: 4660-4671.
7.
Japaze H, Emina J, Diaz C, et al. “Pure” invasive apocrine carcinoma of the breast: a new clinicopathological entity? Breast 2005; 14: 3-10.
8.
Dellapasqua S, Maisonneuve P, Viale G, et al. Immunohistochemically defined subtypes and outcome of apocrine breast cancer. Clin Breast Cancer 2013; 13: 95-102.
9.
Vranic S, Tawfik O, Palazzo J, et al. EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast. Mod Pathol 2010; 23: 644-653.
10.
Liu X, Feng C, Liu J, et al. The importance of EGFR as a biomarker in molecular apocrine breast cancer. Hum Pathol 2018; 77: 1-10.
11.
Liu X, Yang Y, Feng X, et al. Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer. Oncotarget 2016; 7: 48905-48917.
12.
Dreyer G, Vandorpe T, Smeets A, et al. Triple negative breast cancer: clinical characteristics in the different histological subtypes. Breast 2013; 22: 761-766.
13.
Kaya H, Bozkurt SU, Erbarut I, et al. Apocrine carcinomas of the breast in Turkish women: hormone receptors, c-erbB-2 and p53 immunoexpression. Pathol Res Pract 2008; 204: 367-371.
14.
Kasashima S, Kawashima A, Ozaki S, et al. Expression of 5α-reductase in apocrine carcinoma of the breast and its correlation with clinicopathological aggressiveness. Histopathology 2012; 60: E51-E57.
15.
Mills AM, Gottlieb CE, Wendroth SM, et al. Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers. Am J Surg Pathol 2016; 40: 1109-1116.
16.
Matsuo K, Fukutomi T, Hasegawa T, et al. Histological and immunohistochemical analysis of apocrine breast carcinoma. Breast Cancer 2002; 9: 43-49.
17.
Tanaka K, Imoto S, Wada N, et al. Invasive apocrine carcinoma of the breast: clinicopathologic features of 57 patients. Breast J 2008; 14: 164-168.
18.
Vranic S, Marchiò C, Castellano I, et al. Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast. Hum Pathol 2015; 46: 1350-1359.
19.
Tsutsumi Y. Apocrine carcinoma as triple-negative breast cancer: novel definition of apocrine-type carcinoma as estrogen/progesterone receptor-negative and androgen receptor-positive invasive ductal carcinoma. Jpn J Clin Oncol 2012; 42: 375-386.
20.
Cha YJ, Jung W, Koo JS. The Clinicopathologic Features of Molecular Apocrine Breast Cancer. Korean J Pathol 2012; 46: 169-176.
21.
Darb-Esfahani S, von Minckwitz G, Denkert C, et al. Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes. BMC Cancer 2014; 14: 546.
22.
Guo W, Wang W, Zhu Y, et al. HER2 status in molecular apocrine breast cancer: associations with clinical, pathological, and molecular features. Int J Clin Exp Pathol 2015; 8: 8008-8017.
23.
Lehmann-Che J, Hamy AS, Porcher R, et al. Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15. Breast Cancer Res 2013; 15: R37.
24.
Lakis S, Kotoula V, Eleftheraki AG, et al. The androgen receptor as a surrogate marker for molecular apocrine breast cancer subtyping. Breast 2014; 23: 234-243.
25.
Montagna E, Maisonneuve P, Rotmensz N, et al. Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome. Clin Breast Cancer 2013; 13: 31-39.
26.
Masuda S. Breast cancer pathology: the impact of molecular taxonomy on morphological taxonomy. Pathol Int 2012; 62: 295-302.
27.
Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 2015; 26: 259-271.
28.
Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 2014; 138: 241-256.
29.
Adamczyk A, Grela-Wojewoda A, Domaga³a-Haduch M, et al. Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting. J Cancer 2017; 8: 131-139.
30.
Takeuchi H, Tsuji K, Ueo H, et al. Clinicopathological feature and long-term prognosis of apocrine carcinoma of the breast in Japanese women. Breast Cancer Res Treat 2004; 88: 49-54.
31.
d’Amore ES, Terrier-Lacombe MJ, Travagli JP, et al. Invasive apocrine carcinoma of the breast: a long term follow-up study of 34 cases. Breast Cancer Res Treat 1988; 12: 37-44.
32.
Adamczyk A, Niemiec JA, Ambicka A, et al. CD44/CD24 as potential prognostic markers in node-positive invasive ductal breast cancer patients treated with adjuvant chemotherapy. J Mol Histol 2014; 45: 35-45.
33.
Niemiec JA, Adamczyk A, Ambicka A, et al. Prognostic role of lymphatic vessel density and lymphovascular invasion in chemotherapy-naive and chemotherapy-treated patients with invasive breast cancer. Am J Transl Res 2017; 9: 1435-1447.
34.
Untch M, Gerber B, Harbeck N, et al. 13th st. Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus – opinion of a german team of experts (Zurich 2013). Breast Care (Basel) 2013; 8: 221-229.
35.
Liu Y, Yin W, Yan T, et al. The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature. Curr Med Res Opin 2013; 29: 1453-1461.
36.
Petrelli F, Viale G, Cabiddu M, et al. Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients. Breast Cancer Res Treat 2015; 153: 477-491.