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. 2005 May;58(5):509-14.
doi: 10.1136/jcp.2004.020347.

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 Bondi  1 , A Husdal, G Bukholm, J M Nesland, A Bakka, I R K Bukholm
Affiliations

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 Bondi et al. J Clin Pathol. 2005 May.

Abstract

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.

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Figures

Figure 1
Figure 1
Representative examples of immunostaining (original magnification, ×400) for (A) cyclin A, (B) cyclin D3, (C) cyclin E, (D) cyclin C, (E) and cyclin H. (F) An example of cytoplasmic immunopositivity for cyclin B1.
Figure 2
Figure 2
Cyclin A protein expression and survival. The Kaplan–Meier curves show the probability of overall survival in colon adenocarcinoma according to cyclin A protein expression determined by immunohistochemistry. The survival curves were analysed by the log rank test; +, censored data.
Figure 3
Figure 3
CCNC amplification status and survival. The Kaplan–Meier curves show the probability of overall survival in colon adenocarcinoma according to CCNC amplification determined by real time polymerase chain reaction. The survival curves were analysed by the log rank test; +, censored data.
See this image and copyright information in PMC

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