Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression

Åkervall, Jan; Michalides, Rob; Mineta, Hiroyuki; Balm, Alfons J. M.; Borg, Åke; Dictor, Michael; Jin, Yuesheng; Loftus, Barbara; Mertens, Fredrik; Wennerberg, Johan

doi:10.1002/(sici)1097-0142(19970115)79:2<380::aid-cncr22>3.0.co;2-w

Cited by 171 publications

(82 citation statements)

References 26 publications

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“…Loss of CCND1 was significantly associated with nontumor lesions in this study cohort, suggesting genomic instability/chromosomal aneuploidy events in the direction of corresponding gain of CCND1 in tumor lesions ( P < 0.001, univariate analysis). Overexpression and/or amplification of CCND1 is reported in 35%–65% of patients with HNSCC and is associated with poor prognosis [56–58]. Its expression is deregulated in preinvasive lesions adjacent to invasive tumors and is associated with increased chromosomal instability and the likelihood of subsequent gene amplification.…”

Section: Resultsmentioning

confidence: 99%

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Worsham

Lü

Chen

et al. 2012

Journal of Oncology

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Genetic events specific to the pathogenesis of malignancy can offer clues to the tumorigenesis process. The objective of this study was to identify gene alterations that differentiate tumor and nontumor lesions in squamous head and neck cancer (HNSCC). DNA from 220 primary HNSCC with concurrently present tumor and nontumor lesions from the same patient was interrogated for genomic alterations of loss or gain of copy. Conditional logistic regression dealt with tumor and non-tumor records within a patient. Of 113 genes, 53 had univariate effects (P < 0.01), of which 16 genes remained in the multivariable model with P < 0.01. The model had a C-index (ROC) of 0.93. Loss of CDKN2B and gain of BCL6, FGF3, and PTP4A3 predicted tumor. Loss of BAK1 and CCND1 and gain of STCH predicted nontumor. This highly powered model assigned alterations in 16 genes specific for malignant versus nonmalignant lesions, supporting their contribution to the pathogenesis of HNSCC as well as their potential utility as relevant targets for further evaluation as markers of early detection and progression.

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Section: Resultsmentioning

confidence: 99%

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Worsham

Lü

Chen

et al. 2012

Journal of Oncology

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“…There may be two reasons for this difference: First, compared to other subsites in the oral cavity, tongue SCC is characterized by a more aggressive biological phenotype, with a high-degree of cervical lymph node spread that might be reflected at molecular level, such as with cyclin D1 expression. Second, cyclin D1 may be differentially expressed in various anatomical sites in the oral cavity [18], [41], [42]. Regarding ethnicity, two studies previously reported the clinicopathological significance of cyclin D1 overexpression in Caucasian populations.…”

Section: Discussionmentioning

confidence: 99%

Cyclin D1 Overexpression Is Associated with Poor Clinicopathological Outcome and Survival in Oral Squamous Cell Carcinoma in Asian Populations: Insights from a Meta-Analysis

Zhao

et al. 2014

PLoS ONE

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BackgroundThe clinicopathological significance of cyclin D1 overexpression and prognosis of oral squamous cell carcinoma has not been fully quantified. We performed a comprehensive meta-analysis for evaluation of cyclin D1 overexpression in oral squamous cell carcinoma to determine the strength of this association.MethodsUsing both medical subheadings and free terms, we searched PubMed, Embase and the Institute for Scientific Information Web of Science for all eligible studies published before Nov. 2013. We retrieved 1674 citations, determining that 15 met the selection criteria. We used the odds ratio (OR) and hazard ratio (HR) as the common measures of association to quantitatively determine the correlation between cyclin D1 overexpression and outcomes of oral cancer. We performed a meta-analysis and heterogeneity, sensitivity, and subgroup analyses to clarify and validate the pooled results.ResultsThe pooled results provided compelling evidence that cyclin D1 overexpression was significantly correlated with increased tumor size (OR = 1.617, 95% confidence interval [CI] = 1.046–2.498, p = 0.031), lymphoid node metastasis (OR = 2.035, 95% CI = 1.572–2.635, p<0.001), tumor differentiation (OR = 1.976, 95% CI = 1.363–2.866, p<0.001), and advancement of clinical stages (OR = 1.516, 95% CI = 1.140–2.015, p = 0.004), and adversely influenced overall survival of OSCC patients (HR = 1.897, 95% CI = 1.577–2.282, p<0.001). The strength of association varied in different oral cavity subsites.ConclusionOur findings indicated that cyclin D1 expression correlates with detrimental clinicopathological outcome and poor prognosis in oral squamous cell carcinoma. Our results may be useful in the management of oral cancer.

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“…Although this method is a semiquantitative technique, IHC analysis is the most commonly used, simplest, and cheapest protocol in clinical work [30]. Moreover, it is believed that cyclin D1 protein overexpression may occur via other mechanisms besides gene amplification, and the measurement of protein levels would be more informative than cyclin D1 DNA copies [19], [31], [32], [33]. According to the obtained results, low cyclin D1 expression at pretreatment forecasts a better clinical response and an improved DFS and OS in neoadjuvant chemotherapy patients.…”

Section: Discussionmentioning

confidence: 99%

CCND1 as a Predictive Biomarker of Neoadjuvant Chemotherapy in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

et al. 2011

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BackgroundCyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy.Methodology and Findings224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001).ConclusionsThis study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy.

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Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression

Cited by 171 publications

References 26 publications

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Cyclin D1 Overexpression Is Associated with Poor Clinicopathological Outcome and Survival in Oral Squamous Cell Carcinoma in Asian Populations: Insights from a Meta-Analysis

CCND1 as a Predictive Biomarker of Neoadjuvant Chemotherapy in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

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