| Peer-Reviewed

Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy

Received: 7 December 2016     Accepted: 20 December 2016     Published: 19 January 2017
Views:       Downloads:
Abstract

Background: Proliferation is a distinct hallmarks of cancer. Ki-67 designated as a marker of proliferation in solid tumors. The proliferative activity of tumor demonstrated by expression of Ki-67 in breast cancer has been associated with a poor prognosis. Changes in the relative proportions of Ki-67 can be observed during chemotherapy and may correlated with clinical response in breast cancer. Purpose: Evaluate changes in mRNA expression of proliferation marker Ki-67 in breast cancer patients pre- and post-chemotherapy in relation with clinical response to chemotherapy. Method: This is a longitudinal study, 30 subjects breast cancer tissue samples pre- and post-chemotherapy using cyclophosphamide, adriamycin, 5FU regiment. We using qRT-PCR techniques to detect mRNA expression of Ki-67. Chemotherapy response is calculated using RECIST criteria. Results: Mean value of Ki-67 mRNA expression on breast cancer patients pre-chemotheraphy was 11.837±0.360. Mean value of Ki-67 mRNA expression on breast cancer patients post-chemotheraphy was 11.241±1.971. There was no significant correlation between expression of Ki-67 mRNA prechemotherapy with clinical response to chemotherapy, p = 0.862 (p ≥0.05). There is a positive correlation between velocity of Ki-67 mRNA expression with clinical response with value of r = 0.378, this correlation was significant with p = 0.020 (p<0.05). Conclusion: Chemotherapy cause decrease in mRNA expression of Ki-67. There is insignificant correlation between expression of mRNA Ki-67 baseline with chemotherapy response. Velocity of Ki-67 mRNA expression has significant correlation with clinical response to chemotherapy.

Published in American Journal of Clinical and Experimental Medicine (Volume 5, Issue 1)
DOI 10.11648/j.ajcem.20170501.13
Page(s) 10-14
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Breast Cancer, Chemotherapy, mRNA, Ki-67, QRT-PCR

References
[1] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. cell. 2011;144 (5): 646-74.
[2] Scholzen T, Gerdes J. The Ki‐67 protein: from the known and the unknown. Journal of cellular physiology. 2000;182 (3): 311-22.
[3] Van Diest P, Van Der Wall E, Baak J. Prognostic value of proliferation in invasive breast cancer: a review. Journal of clinical pathology. 2004;57 (7): 675-81.
[4] Jones RL, Salter J, A’Hern R, Nerurkar A, Parton M, Reis-Filho JS, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast cancer research and treatment. 2009;116 (1): 53-68.
[5] Goldhirsch A, Winer EP, Coates A, Gelber R, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Annals of oncology. 2013; 24 (9): 2206-23.
[6] Marme F, Schneeweiss A, Aigner J, Eidt S, Altevogt P, Sinn P, et al. Abstract P3-06-08: Ki-67 mRNA as a predictor for response to neoadjuvant chemotherapy in primary breast cancer. Cancer Research. 2012;72(24 Supplement): P3-06-8-P3--8.
[7] Williams SL, Birdsong GG, Cohen C, Siddiqui MT. Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations. Int J Clin Exp Pathol. 2009; 2 (5): 476-80.
[8] Boom R, Sol C, Salimans M, Jansen C, Wertheim-van Dillen P, Van der Noordaa J. Rapid and simple method for purification of nucleic acids. Journal of clinical microbiology. 1990; 28 (3): 495-503.
[9] Mitas M, Mikhitarian K, Walters C, Baron PL, Elliott BM, Brothers TE, et al. Quantitative real‐time RT‐PCR detection of breast cancer micrometastasis using a multigene marker panel. International journal of cancer. 2001; 93 (2): 162-71.
[10] Potemski P, Pluciennik E, Bednarek AK, Kusinska R, Kubiak R, Jesionek-Kupnicka D, et al. Ki-67 expression in operable breast cancer: a comparative study of immunostaining and a real-time RT-PCR assay. Pathology-Research and Practice. 2006; 202 (7): 491-5.
[11] Luangdilok S, Samarnthai N, Korphaisarn K. Association between pathological complete response and outcome following neoadjuvant chemotherapy in locally advanced breast cancer patients. Journal of breast cancer. 2014; 17 (4): 376-85.
[12] Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clinical Cancer Research. 2005;11 (16): 5678-85.
[13] Engstrøm MJ, Opdahl S, Hagen AI, Romundstad PR, Akslen LA, Haugen OA, et al. Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients. Breast cancer research and treatment. 2013; 140 (3): 463-73.
[14] Lønning PE. Poor-prognosis estrogen receptor-positive disease: present and future clinical solutions. Therapeutic advances in medical oncology. 2012: 1758834012439338.
[15] Colleoni M, Montagna E. Neoadjuvant therapy for ER-positive breast cancers. Annals of Oncology. 2012; 23(suppl 10): x243-x8.
[16] Zhang J, Liu Y. HER2 over-expression and response to different chemotherapy regimens in breast cancer. Journal of Zhejiang University Science B. 2008; 9 (1): 5-9.
[17] Hamy-Petit A-S, Belin L, Bonsang-Kitzis H, Paquet C, Pierga J-Y, Lerebours F, et al. Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort. British journal of cancer. 2016; 114 (1): 44-52.
[18] Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. Journal of the National Cancer Institute. 2011.
[19] Luporsi E, André F, Spyratos F, Martin P-M, Jacquemier J, Penault-Llorca F, et al. Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast cancer research and treatment. 2012; 132 (3): 895-915.
[20] Denkert C, Sinn BV, Issa Y, Müller BM, Maisch A, Untch M, et al. Prediction of response to neoadjuvant chemotherapy: new biomarker approaches and concepts. Breast Care. 2011;6 (4): 265-72.
[21] Colozza M, Azambuja E, Cardoso F, Sotiriou C, Larsimont D, Piccart M. Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Annals of oncology. 2005; 16 (11): 1723-39.
[22] Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. The lancet oncology. 2010; 11 (2): 174-83.
[23] Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. Journal of the National Cancer Institute. 2008; 100 (3): 207-12.
[24] Penault-Llorca F, André F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor–positive breast cancer. Journal of Clinical Oncology. 2009;27 (17): 2809-15.
[25] Wirtz RM, Sihto H, Isola J, Heikkilä P, Kellokumpu-Lehtinen P-L, Auvinen P, et al. Biological subtyping of early breast cancer: a study comparing RT-qPCR with immunohistochemistry. Breast cancer research and treatment. 2016: 1-10.
Cite This Article
  • APA Style

    Prihantono Prihantono, Daniel Sampepajung, Andi Asadul Islam, Mochammad Hatta, Warsinggih Rahardjo, et al. (2017). Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy. American Journal of Clinical and Experimental Medicine, 5(1), 10-14. https://doi.org/10.11648/j.ajcem.20170501.13

    Copy | Download

    ACS Style

    Prihantono Prihantono; Daniel Sampepajung; Andi Asadul Islam; Mochammad Hatta; Warsinggih Rahardjo, et al. Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy. Am. J. Clin. Exp. Med. 2017, 5(1), 10-14. doi: 10.11648/j.ajcem.20170501.13

    Copy | Download

    AMA Style

    Prihantono Prihantono, Daniel Sampepajung, Andi Asadul Islam, Mochammad Hatta, Warsinggih Rahardjo, et al. Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy. Am J Clin Exp Med. 2017;5(1):10-14. doi: 10.11648/j.ajcem.20170501.13

    Copy | Download

  • @article{10.11648/j.ajcem.20170501.13,
      author = {Prihantono Prihantono and Daniel Sampepajung and Andi Asadul Islam and Mochammad Hatta and Warsinggih Rahardjo and Christian Binekada and Eddy Herman Tanggo},
      title = {Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {5},
      number = {1},
      pages = {10-14},
      doi = {10.11648/j.ajcem.20170501.13},
      url = {https://doi.org/10.11648/j.ajcem.20170501.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20170501.13},
      abstract = {Background: Proliferation is a distinct hallmarks of cancer. Ki-67 designated as a marker of proliferation in solid tumors. The proliferative activity of tumor demonstrated by expression of Ki-67 in breast cancer has been associated with a poor prognosis. Changes in the relative proportions of Ki-67 can be observed during chemotherapy and may correlated with clinical response in breast cancer. Purpose: Evaluate changes in mRNA expression of proliferation marker Ki-67 in breast cancer patients pre- and post-chemotherapy in relation with clinical response to chemotherapy. Method: This is a longitudinal study, 30 subjects breast cancer tissue samples pre- and post-chemotherapy using cyclophosphamide, adriamycin, 5FU regiment. We using qRT-PCR techniques to detect mRNA expression of Ki-67. Chemotherapy response is calculated using RECIST criteria. Results: Mean value of Ki-67 mRNA expression on breast cancer patients pre-chemotheraphy was 11.837±0.360. Mean value of Ki-67 mRNA expression on breast cancer patients post-chemotheraphy was 11.241±1.971. There was no significant correlation between expression of Ki-67 mRNA prechemotherapy with clinical response to chemotherapy, p = 0.862 (p ≥0.05). There is a positive correlation between velocity of Ki-67 mRNA expression with clinical response with value of r = 0.378, this correlation was significant with p = 0.020 (p<0.05). Conclusion: Chemotherapy cause decrease in mRNA expression of Ki-67. There is insignificant correlation between expression of mRNA Ki-67 baseline with chemotherapy response. Velocity of Ki-67 mRNA expression has significant correlation with clinical response to chemotherapy.},
     year = {2017}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy
    AU  - Prihantono Prihantono
    AU  - Daniel Sampepajung
    AU  - Andi Asadul Islam
    AU  - Mochammad Hatta
    AU  - Warsinggih Rahardjo
    AU  - Christian Binekada
    AU  - Eddy Herman Tanggo
    Y1  - 2017/01/19
    PY  - 2017
    N1  - https://doi.org/10.11648/j.ajcem.20170501.13
    DO  - 10.11648/j.ajcem.20170501.13
    T2  - American Journal of Clinical and Experimental Medicine
    JF  - American Journal of Clinical and Experimental Medicine
    JO  - American Journal of Clinical and Experimental Medicine
    SP  - 10
    EP  - 14
    PB  - Science Publishing Group
    SN  - 2330-8133
    UR  - https://doi.org/10.11648/j.ajcem.20170501.13
    AB  - Background: Proliferation is a distinct hallmarks of cancer. Ki-67 designated as a marker of proliferation in solid tumors. The proliferative activity of tumor demonstrated by expression of Ki-67 in breast cancer has been associated with a poor prognosis. Changes in the relative proportions of Ki-67 can be observed during chemotherapy and may correlated with clinical response in breast cancer. Purpose: Evaluate changes in mRNA expression of proliferation marker Ki-67 in breast cancer patients pre- and post-chemotherapy in relation with clinical response to chemotherapy. Method: This is a longitudinal study, 30 subjects breast cancer tissue samples pre- and post-chemotherapy using cyclophosphamide, adriamycin, 5FU regiment. We using qRT-PCR techniques to detect mRNA expression of Ki-67. Chemotherapy response is calculated using RECIST criteria. Results: Mean value of Ki-67 mRNA expression on breast cancer patients pre-chemotheraphy was 11.837±0.360. Mean value of Ki-67 mRNA expression on breast cancer patients post-chemotheraphy was 11.241±1.971. There was no significant correlation between expression of Ki-67 mRNA prechemotherapy with clinical response to chemotherapy, p = 0.862 (p ≥0.05). There is a positive correlation between velocity of Ki-67 mRNA expression with clinical response with value of r = 0.378, this correlation was significant with p = 0.020 (p<0.05). Conclusion: Chemotherapy cause decrease in mRNA expression of Ki-67. There is insignificant correlation between expression of mRNA Ki-67 baseline with chemotherapy response. Velocity of Ki-67 mRNA expression has significant correlation with clinical response to chemotherapy.
    VL  - 5
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

  • Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

  • Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

  • Molecular Biology and Immunology Laboratory, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

  • Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

  • Department of Surgery, Faculty of Medicine, Haluoleo University, Kendari, Indonesia

  • Department of Surgery, Faculty of Medicine, Airlangga University, Surabaya, Indonesia

  • Sections