Expression of proliferation markers Ki67, cyclin a, geminin and aurora-kinase a in primary breast carcinomas and corresponding distant metastases

Anna Mária Tökés, A. Marcell Szász, Franciska Geszti, Lilla V. Lukács, István Kenessey, Eszter Turányi, Nóra Meggyesházi, István A. Molnár, János Fillinger, Ibolya Soltész, Katalin Bálint, Zoltán Hanzély, Gabriella Arató, Miklós Szendröi, Janina Kulka

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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.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalJournal of Clinical Pathology
Issue number4
Publication statusPublished - Apr 1 2015


ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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