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; Mineta, Hiroyuki; Balm, A. 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>3.3.co;2-5

Cited by 46 publications

(59 citation statements)

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“…Several studies report that patients with HPV-positive head and neck tumours have an improved prognosis (Ritchie et al, 2003;Schlecht, 2005), whereas amplification of 11q13 has been associated with a more rapid and frequent recurrence of disease (Fujii et al, 2001) and poorer survival (Akervall et al, 1997;Rodrigo et al, 2000;Namazie et al, 2002). Weinberger et al (2006) has shown that patients with HPV-positive tumours which express high levels of p16 protein and low levels of p53 protein present with a favourable prognosis.…”

Section: Discussionmentioning

confidence: 99%

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours

et al. 2006

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Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have been proposed, DNA damage owing to tobacco and alcohol exposure and human papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16 mutations or promoter methlyation. However, in HPV þ HNSCC it is frequent to observe wild-type TP53 and expression of p16. The relationship of this unusual pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC patients, only 17% (five out of 30) of HPV þ vs 44% (39 out of 89) of HPV À tumours expressed 11q13 amp (adjusted odds ratio (OR) ¼ 0.2, 95% confidence interval (CI) ¼ 0.1 -0.6). A subpopulation of tumours (n ¼ 69) were classified according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to wild-type TP53, and p16 expression, HPV þ tumours were more likely not to be amplified at 11q13 (OR ¼ 6.5, 95% CI ¼ 1.8 -23.9). As HPV þ HNSCC lack the genetic alterations which are common in other tumours, we hypothesise that HPV infection may represent an early event in the HNSCC carcinogenic process, thus suggesting a distinct molecular pathway.

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Section: Discussionmentioning

confidence: 99%

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours

et al. 2006

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“…Overexpression or amplification of cyclin D1 has been reported to occur in 30% to 50% of head and neck tumors and the importance of overexpression of this protein with respect to local recurrence after uniform treatment has not been clearly defined [2][3][4]. Several retrospective studies have correlated both 11q13 amplification and overexpression of cyclin D1 protein with lymph node positively, metastasis, and decreased overall survival rates [2][3][4]21,22]. However, patients in these studies were treated in a nonuniform manner, thus no clear relationship is evident between cyclin D1 levels and response to individual treatments.…”

Section: Discussionmentioning

confidence: 99%

“…The cyclin D1 gene is located on chromosome 11q13, a region frequently rearranged in many lymphomas and both amplified and overexpressed in carcinomas, including head and neck cancer [2][3][4]. Cyclin D1 is a nuclear protein that has been shown to be an important regulator of G1-S phase transition, and elevated levels of cyclin D1 induce apoptosis [5,6].…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma

Shintani

Mihara

Ueyama

et al. 2001

Intl Journal of Cancer

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SUMMARY Overexpression of cyclin D1, a G1 cell cycle regulator, is often found in many different tumor types, including oral squamous cell carcinomas (SCC). Recent laboratory experiments have demonstrated that cyclin D1 levels can influence radiosensitivity in various cell lines. This study evaluated the relationship between cyclin D1 expression levels and radiosensitivity in nine oral SCC cell lines (HSC2, HSC3, HSC4, SCC15, SCC25, SCC66, SCC111, Ca9-22, and NAN2) and 41 clinical patients with oral SCC who underwent preoperative radiation therapy. Radiosensitivity of the nine oral SCC cell lines differed greatly in their response to radiation, assessed by a standard colony formation assay. Likewise, the expression of cyclin D1 varied, and the magnitude of the cyclin D1 expression correlated with increased tumor radiosensitivity. The similar significant association between the response to preoperative radiation therapy and cyclin D1 overexpression was observed in the oral SCC patients who were treated with preoperative radiation therapy. These results suggest that cyclin D1 expression levels correlate to radiosensitivity and could be used to predict the effectiveness of radiation therapy on oral SCC.

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“…Overexpression of cyclin D1 at both protein and RNA level have been linked to poor prognosis in numerous studies (Akervall et al, 1997;Yu et al, 2005;Higuchi et al, 2007). Cortactin amplification was related to increased lymph node stage, advanced disease stage and reduced survival (Rodrigo et al, 2000).…”

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confidence: 99%

Cortactin expression predicts poor survival in laryngeal carcinoma

et al. 2008

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Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P ¼ 0.016), FADD (P ¼ 0.003) and cortactin (P ¼ 0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter diseasespecific survival in late stage laryngeal carcinomas. Current methods to predict the outcome of head and neck squamous cell carcinoma (HNSCC) patients mainly involve clinicopathological parameters such as tumour size, differentiation grade and presence of lymph node metastasis. Patients with laryngeal squamous cell carcinomas (LSCC) have not shown an increase in 5-year survival rates over the last 30 years (Almadori et al, 2005). Therefore, other parameters such as molecular markers that are able to more accurately predict the outcome of disease, are needed.A frequent molecular event in HNSCC is amplification of the 11q13 region (36%) (Schuuring, 1995;Freier et al, 2006). Amplification of this region in HNSCC has been associated with decreased survival (Akervall et al, 1995;Meredith et al, 1995), increased distant metastasis (Namazie et al, 2002) and lymph node metastasis (Chen et al, 2004;Hermsen et al, 2005;Xia et al, 2007). It is believed that amplification increases gene dosage and expression of genes within the amplified region (amplicon) (Albertson, 2006). Recently, we reported that the commonly amplified region is located at 11q13.3 and contains at least six genes (cyclin D1, TAOS1, FGF19, FADD, PPFIA1 and cortactin) that are overexpressed when amplified (Gibcus et al, 2007b). We concluded that the selection for tumour cells with the 11q13.3 amplicon during tumorigenesis could be based on the increased doses of one or more of these genes. We proposed FADD as a possible candidate for this selection, since FADD showed the best correlation between DNA amplification and increased expression (Gibcus et al, 2007b). Furthermore, FADD protein expression correlated with disease specific mortality (DSM) in a series of late stage laryngeal carcinom...

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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 46 publications

References 5 publications

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma

Cortactin expression predicts poor survival in laryngeal carcinoma

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