Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

Bahnassy, Abeer A.; Zekri, Abdel‐Rahman N.; El-Houssini, Soumaya; El-Shehaby, Amal; Mahmoud, Moustafa R.; Abdallah, Samira; El-Serafi, Mostafa

doi:10.1186/1471-230x-4-22

Cited by 128 publications

(153 citation statements)

References 22 publications

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“…19 Handa et al showed cyclin A overexpression to be associated with poor outcome and to be an independent prognostic factor in colorectal cancer. 20 Bahnassy et al 21 and Nozoe et al 22 have reported similar results concerning colon cancer. In contrast, Li et al showed that cyclin A expression gradually increases in the colon adenoma-carcinoma sequence, but patients with high cyclin A immunoreactivity had better survival than those with reduced cyclin A expression.…”

Section: Discussionsupporting

confidence: 70%

Prognostic significance of cyclin A in gastric cancer

Mrena

Wiksten

Kokkola

et al. 2006

Intl Journal of Cancer

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High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in 5% of the tumor cells was considered the cut-off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the v 2 -test, Fisher's exact test, Kaplan-Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279 of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR. ' 2006 Wiley-Liss, Inc.Key words: cyclin A; HuR; gastric cancer; prognosis; survival Cyclin A belongs to the cyclin protein superfamily, and it can activate two different cyclin-dependent kinases, CDK1 and CDK2. The level of cyclin A accumulates progressively throughout the interphase and disappears rapidly at the end of mitosis. Currently, phosphorylated cyclin A-CDK complex is suggested to play an important role in the initiation of DNA replication in the S phase. The precise function of cyclin A in mitosis is unclear, but it may prevent other cyclins from degradation. Overexpression of cyclin A and dysregulation of CDK-cyclin complexes promote tumor cell growth, which can be facilitated by phosphorylation of oncoproteins and tumor suppressors. 1,2 In gastric cancer, cell-cycle regulators have been connected with poor prognosis. For example, overexpression of cyclin E, which also binds to CDK2 and controls the G1-S transition, has been associated with aggressive disease. 3,4 Furthermore, strongly positive cyclin E in the tumors of patients having surgery with intent to cure is a marker of poor prognosis, and concurrent expression of cyclin E and p53 is an independent prognostic factor. 5 However, there are also reports indicating that cyclin E expression does not correlate with clinicopathological parameters, 6 or is associated with good prognosis. 7 Overexpression of cyclin A correlates with po...

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Section: Discussionsupporting

confidence: 70%

Prognostic significance of cyclin A in gastric cancer

Mrena

Wiksten

Kokkola

et al. 2006

Intl Journal of Cancer

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“…7 Several studies have provided evidence that several molecular markers may be useful in defining the risk for individual patients with CRC after surgery and in identifying patients who may benefit most from adjuvant chemotherapy. 24,31,32 We investigated the possible prognostic and predictive values of c-Kit, COX2, p53, and K-ras in patients with stage II CRC. A novel and interesting finding in the current study is the high frequency of c-Kit overexpression in stage II CRC patients (59.3%) compared with what was reported in other studies.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of c‐Kit, K‐ras codon 12, and p53 codon 72 mutations in Egyptian patients with stage II colorectal cancer

El-Serafi

Bahnassy

Ali

et al. 2010

Cancer

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BACKGROUND:The prognosis for patients with colorectal cancer (CRC) depends mainly on standard clinicopathologic factors. However, patients with similar disease characteristics exhibit various outcomes, especially in stage II. Therefore, the identification of molecular prognostic markers is needed to predict patient outcomes. METHODS: The authors assessed the prognostic value of c-Kit (also called cluster of differentiation 117 [CD117] or KIT), cyclooxygenase-2 (COX-2), tumor protein 53 (p53), and Kirsten rat sarcoma viral oncogene homolog (K-ras) aberrations in 90 patients with stage II CRC using immunohistochemistry and molecular techniques. The results were correlated with standard clinicopathologic prognostic factors, overall survival (OS), and disease-free survival (DFS). RESULTS: COX2 and c-Kit overexpression was detected in 54.6% and 59.3% of patients, respectively. Overexpression of p53 was detected in 47 patients, including 29 who had mutations, and a unique mutation pattern was detected with 3 hotspots at codons 72, 245, and 273. Overexpression of ras was detected in 44 patients, including 37 who had mutations. On multivariate analysis, c-Kit overexpression, p53 codon 72 mutations, perforation, and performance status were independent prognostic factors for DFS (P ¼ .054, P ¼ .015, P < .0001, and P ¼ .043, respectively); whereas codon 12 K-ras mutation, performance status, and perforation were independent prognostic factors for OS (P ¼ .033, P ¼ .006, and P < .0001, respectively). CONCLUSIONS: The current results provide evidence for the prognostic value of c-Kit overexpression in patients with stage II CRC. The high p53 mutation rate and the unique hotspot in codon 72 have not been reported previously in CRC. This may be related to environmental or racial features that are unique to the studied population. Cancer 2010;116:4954-64.

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“…Therefore, upregulation of these genes may contribute to growth inhibition in ATRA-treated Wilms tumor cells. CCNA2 and CKS2 are well-known cell cycle checkpoint genes whose overexpression was linked to cell proliferation and tumor progression (Urbanowicz-Kachnowicz et al, 1999;Bahnassy et al, 2004). Hence, downregulation of these genes in Wilms tumors may convey antiproliferative effects.…”

Section: Genes Involved In Cell Proliferation and Matrix Remodelingmentioning

confidence: 99%

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

Zirn

Samans

Spangenberg³

et al. 2005

Oncogene

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Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

Abstract: Background: Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer.

Cited by 128 publications

References 22 publications

Prognostic significance of cyclin A in gastric cancer

Prognostic significance of cyclin A in gastric cancer

The prognostic value of c‐Kit, K‐ras codon 12, and p53 codon 72 mutations in Egyptian patients with stage II colorectal cancer

All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo

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