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Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases
  1. Anna-Mária Tökés1,2,
  2. A Marcell Szász2,
  3. Franciska Geszti2,3,
  4. Lilla V Lukács4,
  5. István Kenessey2,
  6. Eszter Turányi5,
  7. Nóra Meggyesházi5,
  8. István A Molnár6,
  9. János Fillinger7,
  10. Ibolya Soltész7,
  11. Katalin Bálint5,8,
  12. Zoltán Hanzély8,9,
  13. Gabriella Arató10,
  14. Miklós Szendröi10,
  15. Janina Kulka2
  1. 1MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
  2. 22nd Department of Pathology, Semmelweis University, Budapest, Hungary
  3. 3Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary
  4. 4Department of Radiology, Ministry of Defense State Health Centre, Budapest, Hungary
  5. 51st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
  6. 61st Department of Surgery, Semmelweis University, Budapest, Hungary
  7. 7Department of Pathology, Korányi National Institute for Tuberculosis and Pulmonology, Budapest, Hungary
  8. 8Department of Pathology, National Institute of Neurosurgery, Budapest, Hungary
  9. 9Department of Neuropathology, Southern General Hospital, Glasgow, UK
  10. 10Department of Orthopaedics, Semmelweis University, Budapest, Hungary
  1. Correspondence to Dr Anna-Mária Tökés, MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, 93 Üllöi út, Budapest 1091, Hungary, tokesa1972{at}


Aims To assess the expression of the following cell cycle regulatory proteins in primary metastatic breast carcinomas (MBCs) and on availability in matched distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA); and to compare the expression of these markers in early MBC (EMBC) and late MBC separated into groups according to median time point on metastatic event occurred (28 months).

Methods The expression of the above mentioned markers was analysed in a total of 47 primary MBCs and 59 DMs (out of which 37 were pairs) by immunohistochemistry. Fourteen breast carcinomas with no relapse over a 10-year follow-up period were utilised as control cases (CBC).

Results Among the MBCs, 22 metastasised to the bone, 4 to the lung and 21 to the central nervous system (CNS). Geminin (p<0.001) and Ki67 (p=0.001) were increased in the MBCs while aurkA and cyclin A showed no difference when compared with CBCs. There were no differences between aurkA, cyclin A and geminin expression in MBCs and DMs in general. Expression of Ki67 was, however, elevated (p=0.027) in DMs. In CNS metastases all markers showed elevated expression as compared to MBCs. In bone metastases, geminin was lower (p<0.001) compared with primary MBCs. In the metastases of the lung, the evaluated markers did not show different expression. According to the median follow-up until the metastatic event, Ki67 was found to be significantly elevated in EMBC (p=0.018).

Conclusions Ki67 index and geminin distinguish a fraction of MBC with worse prognosis, showing increased levels in the latter in comparison to CBC being tumour-free over a 10-year follow-up period. Ki67 could possibly identify a group of MBCs that develop early DMs.


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