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

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2005 Apr 29

PMID 15858123

Citations 31

Authors

J Bondi

A Husdal

G Bukholm

J M Nesland

A Bakka

I R K Bukholm

Affiliations

Soon will be listed here.

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.

Citing Articles

Prognostic Significance of Cyclin D1 Expression in Small Intestinal Adenocarcinoma.

Jun S, Hong S, Jang K Cancers (Basel). 2023; 15(20).

PMID: 37894399 PMC: 10604933. DOI: 10.3390/cancers15205032.

Prognostic Biomarkers of Cell Proliferation in Colorectal Cancer (CRC): From Immunohistochemistry to Molecular Biology Techniques.

Kasprzak A Cancers (Basel). 2023; 15(18).

PMID: 37760539 PMC: 10526446. DOI: 10.3390/cancers15184570.

Prognostic Potential of Cyclin D1 Expression in Colorectal Cancer.

Jun S, Kim J, Yoon N, Maeng L, Byun J J Clin Med. 2023; 12(2).

PMID: 36675501 PMC: 9867305. DOI: 10.3390/jcm12020572.

Cuproptosis regulator-mediated patterns associated with immune inﬁltration features and construction of cuproptosis-related signatures to guide immunotherapy.

Wang G, Xiao R, Zhao S, Sun L, Guo J, Li W Front Immunol. 2022; 13:945516.

PMID: 36248857 PMC: 9559227. DOI: 10.3389/fimmu.2022.945516.

Association of , , , , and Genes in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Yan H, Jiang F, Yang J Genet Res (Camb). 2022; 2022:5338956.

PMID: 36072013 PMC: 9402361. DOI: 10.1155/2022/5338956.

References

Li H, Lahti J, Valentine M, Saito M, Reed S, Look A . Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors. Genomics. 1996; 32(2):253-9. DOI: 10.1006/geno.1996.0112. View

Kitahara K, Yasui W, Kuniyasu H, Yokozaki H, Akama Y, Yunotani S . Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas. Int J Cancer. 1995; 62(1):25-8. DOI: 10.1002/ijc.2910620107. View

Nasmyth K . Viewpoint: putting the cell cycle in order. Science. 1996; 274(5293):1643-5. DOI: 10.1126/science.274.5293.1643. View

Lengauer C, Kinzler K, Vogelstein B . Genetic instability in colorectal cancers. Nature. 1997; 386(6625):623-7. DOI: 10.1038/386623a0. View

Sutter T, Doi S, Carnevale K, Arber N, Weinstein I . Expression of cyclins D1 and E in human colon adenocarcinomas. J Med. 1997; 28(5-6):285-309. View

Hengartner C, Myer V, Liao S, Wilson C, Koh S, Young R . Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell. 1998; 2(1):43-53. DOI: 10.1016/s1097-2765(00)80112-4. View

Bieche I, Olivi M, Champeme M, Vidaud D, Lidereau R, Vidaud M . Novel approach to quantitative polymerase chain reaction using real-time detection: application to the detection of gene amplification in breast cancer. Int J Cancer. 1998; 78(5):661-6. DOI: 10.1002/(sici)1097-0215(19981123)78:5<661::aid-ijc22>3.0.co;2-i. View

Palmqvist R, Stenling R, Oberg A, Landberg G . Expression of cyclin D1 and retinoblastoma protein in colorectal cancer. Eur J Cancer. 1999; 34(10):1575-81. DOI: 10.1016/s0959-8049(98)00162-2. View

Furihata M, Ohtsuki Y, Sonobe H, Shuin T, Yamamoto A, Terao N . Cyclin A overexpression in carcinoma of the renal pelvis and ureter including dysplasia: immunohistochemical findings in relation to prognosis. Clin Cancer Res. 1997; 3(8):1399-404. View

10.

Aaltomaa S, Eskelinen M, Lipponen P . Expression of cyclin A and D proteins in prostate cancer and their relation to clinopathological variables and patient survival. Prostate. 1999; 38(3):175-82. DOI: 10.1002/(sici)1097-0045(19990215)38:3<175::aid-pros1>3.0.co;2-#. View

11.

Handa K, Yamakawa M, Takeda H, Kimura S, Takahashi T . Expression of cell cycle markers in colorectal carcinoma: superiority of cyclin A as an indicator of poor prognosis. Int J Cancer. 1999; 84(3):225-33. DOI: 10.1002/(sici)1097-0215(19990621)84:3<225::aid-ijc5>3.0.co;2-a. View

12.

Hanahan D, Weinberg R . The hallmarks of cancer. Cell. 2000; 100(1):57-70. DOI: 10.1016/s0092-8674(00)81683-9. View

13.

Collecchi P, Santoni T, Gnesi E, Naccarato A, Passoni A, Rocchetta M . Cyclins of phases G1, S and G2/M are overexpressed in aneuploid mammary carcinomas. Cytometry. 2000; 42(4):254-60. DOI: 10.1002/1097-0320(20000815)42:4<254::aid-cyto6>3.3.co;2-j. View

14.

Akoulitchev S, Chuikov S, Reinberg D . TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature. 2000; 407(6800):102-6. DOI: 10.1038/35024111. View

15.

Florenes V, Faye R, Maelandsmo G, Nesland J, Holm R . Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res. 2000; 6(9):3614-20. View

16.

Garrett S, Barton W, Knights R, Jin P, MORGAN D, Fisher R . Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop. Mol Cell Biol. 2000; 21(1):88-99. PMC: 88783. DOI: 10.1128/MCB.21.1.88-99.2001. View

17.

Bukholm I, Bukholm G, Nesland J . Over-expression of cyclin A is highly associated with early relapse and reduced survival in patients with primary breast carcinomas. Int J Cancer. 2001; 93(2):283-7. DOI: 10.1002/ijc.1311. View

18.

Korenaga D, Takesue F, Yasuda M, Honda M, Nozoe T, Inutsuka S . The relationship between cyclin B1 overexpression and lymph node metastasis in human colorectal cancer. Surgery. 2002; 131(1 Suppl):S114-20. DOI: 10.1067/msy.2002.119362. View

19.

Latif Z, Watters A, Bartlett J, Underwood M, Aitchison M . Gene amplification and overexpression of HER2 in renal cell carcinoma. BJU Int. 2002; 89(1):5-9. View

20.

Platzer P, Upender M, Wilson K, Willis J, Lutterbaugh J, Nosrati A . Silence of chromosomal amplifications in colon cancer. Cancer Res. 2002; 62(4):1134-8. View