ORIGINAL ARTICLE

Expression and gene amplification of primary (A, B1, D1, D3, and E) and secondary (C and H) cyclins in colon adenocarcinomas and correlation with patient outcome

J Bondi¹, A Husdal², G Bukholm², J M Nesland³, A Bakka¹ and I R K Bukholm¹

¹ Department of Surgery, Akershus University Hospital, N-1474 Nordbyhagen, Norway
² Institute of Clinical Epidemiology and Molecular Biology (Epi-Gen), Akershus University Hospital
³ Department of Pathology, The Norwegian Radium Hospital, N-0310 Oslo, Norway

Correspondence to:
Correspondence to:
Dr I R K Bukholm
Department of Surgery, Akershus University Hospital, N-1474 Nordbyhagen, Norway; ida.bukholm{at}klinmed.uio.no

Background/Aims: Deregulation of cell cycle control is a hallmark of cancer. The primary cyclins (A, B1, D1, D3, and E) are crucial for cell cycle progression. Secondary cyclins (C and H) have putative indirect effects on cell cycle progression and have not previously been evaluated in colon cancer. This study examined cyclin protein expression and gene amplification in colon adenocarcinoma and the correlation with patient outcome.

Methods: Immunohistochemistry and real time quantitative polymerase chain reaction were used to determine cyclin expression and gene amplification in 219 tumours. The results were compared with clinical variables and patient outcomes.

Results: Cyclin H was overexpressed in all tumours, cyclin C in 88%, cyclin B1 in 58%, cyclin A in 83%, cyclin D3 in 36%, cyclin E in 25%, and cyclin D1 in 11% of the tumours. Extra gene copies of cyclin A were seen in 6.2% of the tumours, cyclin B1 in 9%, cyclin C in 26.9%, cyclin D1 in 55%, cyclin D3 in 20.5%, cyclin E in 19.1%, and cyclin H in 5.1%. A significant correlation between protein overexpression and gene amplification was seen for cyclin C only. High expression of cyclin A was independently associated with improved survival. Amplification of cyclin C was independently associated with an unfavourable prognosis.

Conclusions: Amplification of the cyclin C gene was related to an unfavourable prognosis and high protein expression of cyclin A was associated with a better outcome in colon adenocarcinoma.

Abbreviations: Cdk, cyclin dependent kinase; CI, confidence interval; HR, hazards ratio; HSA, human serum albumin; PCR, polymerase chain reaction

Keywords: colon cancer; cyclin; gene amplification; prognosis; protein expression

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