Expressions and clinical significances of TK1 and Ki-67 in triple negative breast cancer

doi:10.3760/cma.j.issn.1673-422X.2016.06.003

Abstract

Abstract: Objective To analyze the expressions of thymidine kinase 1 (TK1) and nuclearassociated antigen Ki-67 in triple negative breast cancer (TNBC) and their clinical significances. MethodsOne hundred and twenty tumor tissue sections of patients with breast cancer who were performed breast conservation treatment or modified mastectomy in the Second Affiliated Hospital of Qingdao University Medical College from June 2009 to December 2010 were collected, and there were 60 cases with TNBC and 60 cases with nonTNBC. The expressions of TK1 and Ki-67 in different breast tissues were detected by immunohistochemistry. The relationships between the expression status and clinicopathologic features were analyzed. ResultsThe positive expression rates of TK1 in TNBC and nonTNBC were 83.33% and 51.67% respectively, with a significant difference (χ2=13.713, P=0.000). The positive expression rates of Ki67 expression in TNBC and nonTNBC were 68.33% and 31.67% respectively, with a significant difference (χ2=16.133, P=0.000). In TNBC, the expression of TK1 was related to histological staging (χ2=6.125, P=0.013), but it was not related to onset age (χ2=0.809, P=0.369), menopausal stutas (χ2=1.615, P=0.204), tumor size (χ2=0.054, P=0.816) and lymphatic metastasis (χ2=0.672, P=0.412). In TNBC, the expression of Ki67 was related to histological staging (χ2=13.145, P=0.000) and lymphatic metastasis (χ2=6.182, P=0.013), but it was not related to menopausal stutas (χ2=1.018, P=0.313), onset age (χ2=2.377, P=0.123) and tumor size (χ2=2.401, P=0.121). The expression of TK1 was positively correlated with that of Ki67 (r=0.369, P=0.023). The results of survival analysis showed that the diseasefree survival rates of 5year were 28.20% and 66.70% in the TK1 positive group and TK1 negative group, and the diseasefree survival rates of 5year were 24.30% and 64.30% in the Ki-67 positive group and Ki-67 negative group, with significant differences (χ2=4.194, P=0.041; χ2=4.540, P=0.033). ConclusionTK1 and Ki-67 are highly expressed in TNBC, and their expressions are correlated with histological staging and survival, which are expected to become prognostic indicators.

Key words: Thymidine kinase, Proliferating cell nuclear antigen, Breast neoplasms

Niu Yuchao*, Yao Yuan, Ma Xuezhen. Expressions and clinical significances of TK1 and Ki-67 in triple negative breast cancer[J]. Journal of International Oncology, 2016, 43(6): 409-413.

References

［1］ Bryan BB, Schnitt SJ, Collins LC. Ductal carcinoma in situ with basallike phenotype: a possible precursor to invasive basallike breast cancer［J］. Mod Pathol, 2006, 19(5): 617-621. DOI: 10.1038/modpathol.3800570. ［2］ Johnson LF, Rao LG, Muench AJ. Regulation of thymidine kinase enzyme level in serumstimulated mouse 3T6 fibroblasts［J］. Exp Cell Res, 1982, 138(1): 79-85. DOI: 10.1016/00144827(82)900933. ［3］刘广舒, 高云, 郭鹏, 等. C-erbB-2、Ki-67、nm23基因表达与乳腺癌腋窝淋巴结转移的相关性分析［J］. 实用预防医学, 2013, 20(3): 340-342. DOI: 10.3969j.issn.10063110.2013.03.032. ［4］王红梅, 魏尚典, 陈新文, 等. Ki67在乳腺癌中的表达及临床意义［J］. 中国普通外科杂志, 2012, 21(5): 616618. ［5］ He Q, Mao Y, Wu J, et al. Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas［J］. Int J Oncol, 2004, 25(4): 945-953. DOI: 10.3892/ijo.25.4.945. ［6］ Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and longterm survival in patients with triplenegative breast cancer［J］. J Clin Oncol, 2008, 26(8): 1275-1281. DOI: 10.1200/JCO.2007.14.4147. ［7］ Korsching E, Packeisen J, Agelopoulos K, et al. Cytogenetic alterations and cytokeratin expression patterns in breast cancer: integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis［J］. Lab Invest, 2002, 82(11): 1525-1533. DOI: 10.1097/01.LAB.0000038508.86221.B3. ［8］ Matos I, Dufloth R, Alvarenga M, et al. p63, cytokeratin 5, and Pcadherin: three molecular markers to distinguish basal phenotype in breast carcinomas［J］. Virchows Archiv, 2005, 447(4): 688-694. DOI: 10.1007/s00428-005-0010-7. ［9］杨雅洁, 温文, 关弘, 等. 乳腺癌中胸苷激酶1的表达及其临床意义［J］. 临床与实验病理学杂志, 2012, 28(5): 562-564. ［10］ He Q, Fornander T, Johansson H, et al. Thymidine kinase 1 in serum predicts increased risk of distant or locoregional recurrence following surgery in patients with early breast cancer［J］. Anticancer Res, 2006, 26(6C): 47534759. ［11］李斌, 曹剑霞, 成红霞, 等. 血清TK1含量在乳腺癌患者中的变化及临床意义［J］. 放射免疫学杂志, 2012, 25(5): 587-588. DOI: 10.3969/j.issn.10089810.2012.05.058. ［12］ Tan PH, Bay BH, Yip G, et al. Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death［J］. Med Pathol, 2005, 18(3): 374-381. ［13］李延辉. 乳腺增生性病变组织中ER、PR、c-erbB-2、p16和Ki-67的表达及意义［J］. 实用预防医学, 2009, 16(5): 1509-1511. ［14］阮永威, 田兴松, 侯连泽. 乳腺癌p16, p53基因蛋白和mRNA的表达及其意义［J］. 中国普通外科杂志, 2008, 17(5): 497-501. ［15］李振凤, 宋修岐, 邹晓, 等. 乳癌组织LRP16、Ki67及EGFR表达及其与预后关系［J］. 齐鲁医学杂志, 2013, 28(2): 124-126. DOI: 10.1172/qlyx201302010. ［16］付荣湛, 阮长乐, 于学智, 等. Ki67和DNA倍体与乳腺癌淋巴转移倾向［J］. 肿瘤学杂志, 2003, 9(6): 350-352. ［17］ Ceccarelli C, Trerè D, Santini D, et al. AgNORs in breast tumours［J］. Micron, 2000, 31(2): 143-149. ［18］任若冰, 许頳, 李亚芬, 等. 血清胸苷激酶1在乳腺肿瘤中的表达及其临床意义［J］. 中国癌症杂志, 2014, 24(1): 41-45. DOI: 10.3969/j.issn.1007-3969.2014.01.007.

[1]	Wang Ying, Liu Nan, Guo Bing. Advances of antibody-drug conjugate in the therapy of metastatic breast cancer [J]. Journal of International Oncology, 2024, 51(6): 364-369.
[2]	Sa Qiang, Xu Hangcheng, Wang Jiayu. Advances in immunotherapy for breast cancer [J]. Journal of International Oncology, 2024, 51(4): 227-234.
[3]	Yang Zhi, Lu Yiqiao, Gu Huayan, Ding Jialing, Guo Guilong. Research progress of tumor microenvironment mediated drug resistance in targeted therapy of breast cancer [J]. Journal of International Oncology, 2024, 51(4): 235-238.
[4]	Chen Boguang, Wang Sugui, Zhang Yongjie. Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer [J]. Journal of International Oncology, 2024, 51(2): 73-82.
[5]	Gu Huayan, Zhu Teng, Guo Guilong. Breast microbiota and breast cancer： present and future [J]. Journal of International Oncology, 2024, 51(1): 55-58.
[6]	Wang Jing, Xu Wenting. Value of NLR， CEA combined with coagulation indicators in the differential diagnosis of benign and malignant breast nodules with a diameter ≤ 1.0 cm [J]. Journal of International Oncology, 2023, 50(9): 520-526.
[7]	Feng Chengtian, Huang Furong, Cao Shiyu, Wang Jianyu, Nanding Abiyasi, Jiang Yongdong, Zhu Juanying. Relationships between HER2 protein expression and imaging features in HER2 positive breast cancer patients [J]. Journal of International Oncology, 2023, 50(9): 527-531.
[8]	Feng Dongxu, Wu Wei, Gao Pingfa, Wang Jun, Shi Lijuan, Chen Dawei, Li Wenbing, Zhang Meifeng. Effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating Rho/ROCK1 pathway [J]. Journal of International Oncology, 2023, 50(8): 449-456.
[9]	Pan Shulan, Liu Chang, He Ping. Effect of fritinib on angiogenesis, tumor growth and IRE1-ASK1-JNK pathway in triple negative breast cancer [J]. Journal of International Oncology, 2023, 50(8): 457-462.
[10]	Wang Wende, Zeng De. Research progress on the mechanism of endocrine therapy resistance for breast cancer [J]. Journal of International Oncology, 2023, 50(6): 352-356.
[11]	Li Qingshan, Xie Xin, Zhang Nan, Liu Shuai. Research progress on the application of combining radiotherapy and systemic therapy in breast cancer [J]. Journal of International Oncology, 2023, 50(6): 362-367.
[12]	Zhu Jun, Huang Meijin, Li Yuan, Liu Zegang, Xun Xin, Chen Hong. Research progress on targeted therapy of breast cancer with low expression of HER2 [J]. Journal of International Oncology, 2023, 50(4): 236-240.
[13]	Zhou Ting, Xu Shaohua, Mei Lin. Efficacy and safety of bevacizumab combined with capecitabine in the treatment of advanced breast cancer [J]. Journal of International Oncology, 2023, 50(3): 144-149.
[14]	Li Lixi, Zhang Di, Luo Yang, Ma Fei. Clinical application of PARP inhibitors in breast cancer [J]. Journal of International Oncology, 2023, 50(2): 91-96.
[15]	Geng Rui, Ma Junqiang, Guo Qiang, Niu Zhaofeng. Tendency of elderly patients with breast cancer to choose comprehensive treatment mode and its influencing factors [J]. Journal of International Oncology, 2023, 50(11): 650-654.