C-kit overexpression correlates with KIT gene copy numbers increases in phyllodes tumors of the breast

详细信息    查看全文

• 作者：Junjun Liu ; Xiaozhen Liu ; Xiaolong Feng ; Jian Liu…
• 关键词：Breast ; Phyllodes tumors ; c ; Kit ; Copy number variation ; Overexpression
• 刊名：Breast Cancer Research and Treatment
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：149
• 期：2
• 页码：395-401
• 全文大小：958 KB
• 参考文献：1. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, Van der Vijver MJ (2012) WHO classification of tumours of the breast. WHO, Geneva
  2. Lv S, Niu Y, Wei L, Liu Q, Wang X, Chen Y (2008) Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study. Breast Cancer Res Treat 112:411-18 CrossRef
  3. Bose P, Dunn ST, Yang J, Allen R, El-Khoury C, Tfayli A (2010) c-Kit expression and mutations in phyllodes tumors of the breast. Anticancer Res 30(11):4731-736
  4. Esposito NN, Mohan D, Brufsky A, Lin Y, Kapali M, Dabbs DJ (2006) Phyllodes tumor—a clinicopathologic and immunohistochemical study of 30 cases. Arch Pathol Lab Med 130(10):1516-521
  5. Ili? I, Randelovi? P, Ili? R, Kati? V, Milentijevi? M, Velickovi? L, Krsti? M (2009) An approach to malignant mammary phyllodes tumor. Vojnosanit Pregl 66(4):277-82 CrossRef
  6. Tse GM, Putti TC, Lui PC, Lo AW, Scolyer RA, Law BK, Karim R, Lee CS (2004) Increased c-kit (CD117) expression in malignant mammary phyllodes tumors. Mod Pathol 17(7):827-31 CrossRef
  7. Tan PH, Jayabaskar T, Yip G, Tan Y, Hilmy M, Selvarajan S, Bay BH (2005) p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study. Mod Pathol 18(12):1527-534
  8. Carvalho S, e Silva AO, Milanezi F, Ricardo S, Leitao D, Amendoeira I, Schmidt FC (2004) c-Kit and PDGFRA in breast phyllodes tumours: overexpression without mutations? J Clin Pathol 57(10):1075-079 CrossRef
  9. Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hillmy M, Hung H, Selvarajan S, Bay BH (2005) Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol 123:529-40 CrossRef
  10. Tan WJ, Thike AA, Tan SY, Tse GM, Tan MH, Bay BH, Tan PH (2014) CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival. Mod Pathol. doi:10.1038/modpathol.2014.111
  11. Liang J, Wu YL, Chen BJ, Zhang W, Tanaka Y, Sugiyama H (2013) The c-kit receptor-mediated signal transduction and tumor-related diseases. Int J Biol Sci 9(5):435-43 CrossRef
  12. Bernex F, De Sepulveda P, Kress C, Elbaz C, Delouis C, Panthier JJ (1996) Spatial and temporal patterns of c-kit-expressing cells in WlacZ/+ and WlacZ/WlacZ mouse embryos. Development 122:3023-033
  13. Ogawa M, Nishikawa S, Yoshinaga K, Hayashi S, Kunisada T, Nakao J, Kina T, Sudo T, Kodama H, Nishikawa S (1993) Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-kit-independent to the late c-kit-dependent wave of hemopoiesis in the murine embryo. Development 117:1089-098
  14. Spritz RA (1994) Molecular basis of human piebaldism. J Invest Dermatol 103:137S-40S CrossRef
  15. Heinrich MC, Blanke CD, Druker BJ, Corless CL (2002) Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20:1692-703 CrossRef
  16. Dybko J, Haus O, Jazwiec B, Urbaniak J, Wozniak M, Kaczmar-Dybko A, Urbaniak-Kujda D, Kapelko-Slowik K, Kuliczkowski K (2014) CD117 (c-kit) expression on CD34+?cells participates in the cytogenetic response to imatinib in patients with chronic myeloid leukemia in the first chronic phase. Acta Haematol 132(2):166-71 CrossRef
  17. Natali PG, Nicotra MR, Sures I, Mottolese M, Botti C, Ullrich A (1992) Breast cancer is associated with loss of the c-kit oncogene product. Int J Cancer 52:713-17 CrossRef
  18. Tsuura Y, Suzuki T, Honma K, Sano M (2002) Expression of c-kit protein in proliferative lesions of human breast: sexual difference and close association with phosphotyrosine status. J Cancer Res Clin Oncol 12
• 作者单位：Junjun Liu (1)
  Xiaozhen Liu (1)
  Xiaolong Feng (1)
  Jian Liu (1)
  Shuhua Lv (1) (2)
  Wei Zhang (1)
  Yun Niu (1)
  
  1. Department of Breast Cancer Pathology and Research Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China
  2. Department of Pathology, Nankai University Affiliated Hospital, 190, Jie-Yuan Road, Hong Qiao District, Tianjin, 300121, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

We determined c-kit expression in the stroma and epithelia of benign, borderline, and malignant phyllodes tumors (PTs), respectively, as well as the relationship between c-kit expression in stromal elements and KIT gene copy number variations (CNVs). To assess c-kit expression and KIT CNVs, 348 PT cases were studied: 120 (34.4?%) benign cases, 115 (33.1?%) borderline cases, and 113 (32.5?%) malignant cases. All of these cases were evaluated for c-kit (CD117) expression using immunohistochemistry. Forty-two cases (29 c-kit-positive in the stromal cells cases and 13 negative cases) were investigated for KIT gene CNVs via genomic polymerase chain reaction (PCR). The overall rate of c-kit positivity in the stroma was 46.8?%, as well as 24.2, 53.1, and 64.6?%, respectively, in PTs of three different grades. However, in the majority of cases, the epithelia were c-kit positive (98.2?%), and the positivity was 100, 99.1, and 95?% in PTs of three different grades, respectively. There was a significant change in the expression of c-kit in the stroma and epithelia according to grade (P?P?=?0.014). From the genomic PCR results, we can confirm that c-kit positivity in the stroma is directly correlated with KIT gene copy numbers increases (P?=?0.003, P?=?0.041). We demonstrated that c-kit expression in the stroma of PTs is positively associated with malignancy. c-Kit epithelial positivity was inversely correlated with PTs malignancy. c-Kit overexpression in the stroma was related to KIT gene copy numbers increases.