CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma - PubMed (original) (raw)

doi: 10.1371/journal.pone.0026399. Epub 2011 Oct 31.

Wei Guo, Chenping Zhang, Qin Xu, Ping Zhang, Jian Sun, Hanguang Zhu, Zhonghe Wang, Jiang Li, Lizhen Wang, Bingshun Wang, Guoxin Ren, Tong Ji, Wenyong Tu, Xihu Yang, Weiliu Qiu, Li Mao, Zhiyuan Zhang, Wantao Chen

Affiliations

CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma

Zhien Feng et al. PLoS One. 2011.

Abstract

Background: Cyclin 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 findings: 224 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).

Conclusions: This 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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Two typical cases with low and high cyclin D1 expression were tested by cytokeratin stain.

Figs. A–D: The low cyclin D1 expression case. A. HE stain (400cyclin D1 expression were tested by cytok D1 stain (400 case. P-CK stain (40000 cases. E–H: The high cyclin D1 expression case. E. HE stain (400cyclin D1 expression were tested by cytok D1 stain (400×); H. P-CK stain (40000×).

Figure 2

Figure 2. Kaplan-Meier survival curves for different treatment protocols and biomarker as well as the impact of treatment procedure according to CCND1 expression.

References

    1. Ferlay JSH, Bray F, Forman D, Mathers CD, Parkin D. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. Lyon, France: International Agency for Research on Cancer Cancer; Year. 2010. Available: http://globocan.iarc.fr. 2010. Last accessed 8/17/2010.
    1. Adelstein DJ, Leblanc M. Does induction chemotherapy have a role in the management of locoregionally advanced squamous cell head and neck cancer? J Clin Oncol. 2006;24:2624–2628. - PubMed
    1. Domenge C, Hill C, Lefebvre JL, De Raucourt D, Rhein B, et al. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tete et du Cou (GETTEC). Br J Cancer. 2000;83:1594–1598. - PMC - PubMed
    1. Paccagnella A, Orlando A, Marchiori C, Zorat PL, Cavaniglia G, et al. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst. 1994;86:265–272. - PubMed
    1. Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355:949–955. - PubMed

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