Prognostic Significance Of Cyclin Research Articles

Prognostic and clinicopathological significance of cyclin B expression in patients with breast cancer: A meta-analysis.

Cyclin B plays a crucial role in cancer cell cycle progression and is overexpressed in many human cancers, including breast cancer. However, the prognostic value of cyclin B expression in breast cancer is controversial. We performed a meta-analysis to assess the clinicopathological and prognostic significance of cyclin B expression in breast cancer. We searched PubMed, web of science, and Embase databases to retrieve the publications investigating the association between cyclin B expression and clinicopathological/prognostic significance in breast cancer patients. The pooled hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CIs) were used to estimate the effects. Ten studies with 2366 breast cancer patients were included to evaluate the association between cyclin B expression and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and clinicopathological parameters. The results showed that cyclin B overexpression in breast cancer patients was significantly associated with both poor OS (univariate analysis: HR = 2.38, 95% CI = 1.72-3.30, P < .001), DFS (univariate analysis: HR = 1.86, 95% CI = 1.50-2.32, P < .001; multivariate analysis: HR = 1.75, 95% CI = 1.22-2.52, P = .003), and DSS (multivariate analysis: HR = 5.42, 95% CI = 2.15-13.66, P < .001). Additionally, cyclin B overexpression was significantly associated with lymphatic invasion (OR = 2.58, 95% CI = 1.03-6.46, P = .017). Cyclin B overexpression appears to be an independent potential prognostic marker to DSS and DFS for breast cancer. Further studies with large sample size are needed to dissect the relationship between cyclin B and clinicopathological features or prognosis of breast cancer.

High expression of cyclin A is associated with poor prognosis in endometrial endometrioid adenocarcinoma

Cyclins are a group of proteins that act as activators to cyclin-dependent kinases and are required for normal cell cycle transitions. Cyclin A is involved in the transitions between G1 to S and G2 to M. Its deregulation has been linked to a number of neoplasms, including endometrial cancer. The prognostic significance of cyclin A expression seems to be cancer-specific, and current knowledge on its impact on survival of endometrial cancer is limited. This study aimed to investigate the effect of cyclin A expression on cancer-specific survival and its correlation with conventional prognostic factors in endometrioid adenocarcinoma. Biopsies obtained from 211 patients were immunohistochemically stained for cyclin A and differences in expression analyzed at the Oulu University Hospital. Patients were divided into two groups utilizing the ROC curve. Further survival analyses were carried out between these two groups. In this study, we show that cyclin A expression correlates with tumor grade and FIGO stage. We also show that cyclin A is an independent prognostic factor in endometrioid adenocarcinoma. Whether cyclin A plays a role in tumorigenesis or merely is a marker of increased proliferation requires further studies.

Clinicopathologic significance and prognostic role of cyclin E and cyclin A expression in laryngeal epithelial lesions

Conclusions. The determination of cyclin A expression might be helpful in the identification of laryngeal squamous cell cancer (LSCC) patients with increased risk of metastases. The results suggest that cyclin A may be a more informative marker for cell proliferation than Ki-67. Abnormalities of cyclin E and cyclin A may play an important role in LSCC development and progression; however, the expression of cyclin E does not seem to have prognostic significance. Objective. The aim of the study was to elucidate a possible association between cyclin E and cyclin A expression and clinicopathologic factors and their potential role as prognostic markers for patients with laryngeal epithelial lesions. Materials and methods. Expression of cyclins E and A, and Ki-67 was examined immunohistochemically in a formalin-fixed, paraffin-embedded series of 46 LSCC; 23 epithelial dysplasias (ED); and 21 normal mucosae (NM). Results. The mean labeling indices (LIs) for cyclin E in LSCC, ED, and NM were 10.6%, 4.9%, and 0%, and for cyclin A 27.2%, 17.5%, and 7%, respectively. In LSCC, a statistically significant correlation was found between enhanced cyclin A expression and a higher incidence of locoregional lymph node metastasis (p<0.01). The enhanced expression of cyclin A was linked with cell proliferation in LSCC, ED, and NM. No association was observed between cyclin E and A and other clinicopathologic parameters or applied treatments. The prognostic significance of cyclin E, cyclin A, and Ki-67 in determining overall survival time showed no statistically significant differences.

Diagnostic and prognostic significance of cyclin A expression in low-grade astrocytomas: comparison with astrogliosis and high-grade tumours

Aim:Definitive distinction between low-grade astrocytoma and astrogliosis is a long-standing difficulty due to their similar histopathological characteristics. To clarify differences in biological significance, this study focused on various components of...

Prognostic significance of Cyclin A in epidermoid anal cancer

Ultimately aiming at a more individualized therapeutic approach in epidermoid anal cancer, this study explored the prognostic and predictive impact of a set of tumour markers. From a population-based cohort of 276 patients with epidermoid anal cancer, treated according to prospective protocols, 215 pre-treatment biopsies were investigated using immunohistochemistry. The expression of p53, p21, Cyclin A and CD31 was measured semi-quantitatively. The expression rate was classified as high when immunostaining was seen in > 5% of the tumour cells for p53 and p21, > 20% in Cyclin A and, above median vessel count for CD31. Marker expression was correlated to survival and treatment response. A high Cyclin A expression correlated significantly with improved overall (77% vs 59%, p = 0.005) and tumour-specific (81% vs 64%, p = 0.009) survival at 5 years. Also, the locoregional failure rate was significantly lower in patients with a high Cyclin A expression (12% vs 24%, p < 0.05). In a multivariate Cox analysis Cyclin A was an independent prognostic factor. A low p21 expression correlated with a reduced rate of locoregional failure (14% vs 27%, p < 0.05) but no impact on survival was found. For p53 and CD31 no significant correlations were obtained. Cyclin A may be an indicator of radiosensitivity and a valuable prognostic marker in epidermoid anal cancer.

Prognostic significance of cyclin A in gastric cancer

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 > or =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 chi2-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.

Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides

Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997–1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers’ results was good or even very good, with kappa values 0.71–0.87. The agreement of TMA and large section results was good with kappa value 0.62–0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

Gene expression signature characterizing cyclin E protein overexpression in primary breast tumors

Abstract Introduction: Cyclin E protein overexpression has been demonstrated to correlate with recurrence in breast cancer, and does not correlate with gene expression on Affymetrix Hu95 microarrays. We sought to identify a gene expression signature characterizing cyclin E protein overexpression using gene expression data on primary breast tumors. Methods: RNA and protein were extracted from forty-four breast carcinoma specimens from the Duke University Breast Cancer SPORE frozen tissue bank. Fluorescently labeled cDNA probe was generated and hybridized to Affymetrix Hu95 gene chips in the Duke University Microarray Core Facility yielding gene expression data. Cyclin E protein expression was measured by tissue western blot. Prediction Analysis of Microarrays software and clustering algorithms were used to identify differentially expressed genes and to make cyclin E protein overexpression predictions. Results: Of 44 tumors, 12 exhibited cyclin E protein overexpression. There was no correlation between protein overexpression and cyclin E gene expression on the gene array. The 91 genes with greatest differential expression were identified. Supervised hierarchical clustering generated a gene expression cluster separating tumors with high versus low cyclin E protein expression with only one misclassification. Cyclin E protein expression was predicted with 92.3% accuracy using gene expression data in preliminary analysis. Conclusions: A pattern of gene expression in breast tumors exhibiting cyclin E protein overexpression has been identified. This gene expression signature can be incorporated in gene expression based models of outcome prediction, perhaps utilizing the prognostic significance of cyclin E protein overexpression.

P-389 Prognostic significance of cyclin E, p27, and pRb in stage I non-small cell lung cancer

P-389 Prognostic significance of cyclin E, p27, and pRb in stage I non-small cell lung cancer

Prognostic significance of cyclin a expression in meningiomas.

Unconstrained cell proliferation is characteristic of tumors. It is caused by the functional disorders of proteins that constitute the cell cycle mechanism. The cell cycle is controlled by cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors. Many reports have proved, in cancers, that cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors are out of control. Cyclin A is a protein that regulates critical transition of the cell cycle. The expression of cyclin A in meningiomas by immunohistochemical method was investigated. Furthermore, the correlation among cyclin A expression, clinical course, and proliferative potential were also evaluated. Seventy-seven meningiomas were studied. The mean cyclin A labeling indices were as follows: benign meningiomas, 1.01% +/- 0.62%; atypical meningiomas, 4.23% +/- 1.82%; and anaplastic meningiomas, 7.72% +/- 0.88%. Analyses of variance showed that significant differences existed between tumor grades for cyclin A labeling indices. A linear positive correlation between the cyclin A labeling index and bromodeoxyuridine labeling index was observed. The multivariate analysis using Cox's hazards model showed a high cyclin A labeling index (>3%) was a significant risk factor for recurrence. A high Ki-67 labeling index (>5%) and high tumor grade (World Health Organization grade II, III) were also significant risk factors for recurrence. These results suggested that the evaluation of cyclin A expression in meningiomas provides significant clinical information, especially as an independent prognostic indicator.

Prognostic significance of cyclin E and p53 protein overexpression in carcinoma of the renal pelvis and ureter.

Cyclin E gene alteration in the cell cycle plays an important role in carcinogenesis, while p53 protein affects different phase checkpoint pathways by activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically examined the expression of cyclin E and p53 proteins in 121 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine their significance for tumour behaviour and patient prognosis. Cyclin E and p53 immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P < 0.05). Mirror-section technique was performed in five selected double-positive tumours to identify cancer cells that were nuclei positive for both cyclin E and p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53 immunostaining was higher in the high-grade tumours (P < 0.01) than in the other types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a significantly poorer prognosis than those expressing neither cyclin E nor p53 (P < 0.001). These in vivo findings provide evidence for cyclin E protein overexpression in TCCs intimately associated with p53 alteration and suggest that simultaneous overexpression of both cyclin E and p53 is related to tumour behaviour and poor prognosis.