title: Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A in primary breast carcinomas and corresponding distant metastases.
abstract: OBJECTIVE
  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.
authors.affiliation: MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Anna-Mária
authors.initials: AM
authors.lastname: Tökés
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: A Marcell
authors.initials: AM
authors.lastname: Szász
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary.
authors.forename: Franciska
authors.initials: F
authors.lastname: Geszti
authors.affiliation: Department of Radiology, Ministry of Defense State Health Centre, Budapest, Hungary.
authors.forename: Lilla V
authors.initials: LV
authors.lastname: Lukács
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Kenessey
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Turányi
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Meggyesházi
authors.affiliation: 1st Department of Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: István A
authors.initials: IA
authors.lastname: Molnár
authors.affiliation: Department of Pathology, Korányi National Institute for Tuberculosis and Pulmonology, Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Fillinger
authors.affiliation: Department of Pathology, Korányi National Institute for Tuberculosis and Pulmonology, Budapest, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Soltész
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary Department of Pathology, National Institute of Neurosurgery, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Bálint
authors.affiliation: Department of Pathology, National Institute of Neurosurgery, Budapest, Hungary Department of Neuropathology, Southern General Hospital, Glasgow, UK.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Hanzély
authors.affiliation: Department of Orthopaedics, Semmelweis University, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Arató
authors.affiliation: Department of Orthopaedics, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Szendröi
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000032:analysis*; D001859:Bone Neoplasms / Q000201:enzymology / Q000556:secondary; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D049109:Cell Proliferation; D016543:Central Nervous System Neoplasms / Q000201:enzymology / Q000556:secondary; D019925:Cyclin A / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D064248:Geminin / Q000032:analysis*; D006801:Humans; D006814:Hungary; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D019925:Cyclin A; C577995:GMNN protein, human; D064248:Geminin; D019394:Ki-67 Antigen; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: BREAST CANCER; IMMUNOHISTOCHEMISTRY; PROLIFERATION