The involvement of the chromosome 11q13 region in human malignancies: Cyclin D1 and EMS1 are two new candidate oncogenes-a review

Schuuring, Ed

doi:10.1016/0378-1119(94)00562-7

Cited by 242 publications

(243 citation statements)

References 88 publications

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“…These carcinoma have stressed that amplification and overexpression of Dl play an important cyclin Dl correlates with poor prognosis (Borg et al, 1991;Schuuring et al, 1992b;Muller et al, 1994). The present study y demonstrated overexshows that, in patients with invasive tumours, there was a lf of 75 urinary bladder tendency for patients with overexpression of cyclin Dl to have a lification of the 1 lq13 worse prognosis than patients with negatively stained tumours for icers (Schuuring, 1995; cyclin Dl, although the correlation between the overexpression of cyclin Dl and actuarial survival was not statistically significant. The weak correlation found between expression of cyclin Dl and actuarial survival in the present study of bladder cancer does not exclude a potential role as a prognostic factor.…”

Section: Discussionsupporting

confidence: 51%

Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

Shin

Kong²,

Kim³

et al. 1997

Br J Cancer

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Summary Cyclin Dl is a cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumour types as a consequence of gene amplification or chromosomal rearrangements. We analysed the expression of cyclin Dl in 75 patients with transitional cell carcinoma (TCC) to investigate the possible relationship between its expression and clinical outcome as well as histopathological findings using the immunohistochemical method. We observed strong staining (++, > 50% positive cells) for cyclin Dl in 19 cases (25.3%) and weak staining (+, 5-50% positive cells) in 19 cases (25.3%). Overexpression of cyclin Dl was not associated with tumour invasion. No significant association was found between overexpression of cyclin Dl and tumour grade (P > 0.05). We assessed the differences of disease-free interval in superficial tumours and actuarial survival probability in invasive tumours according to the status of cyclin Dl expression. Tumours with (++) staining for cyclin Dl recurred much more rapidly than (-) and/or (+) staining tumours (P < 0.01 for -vs ++; P < 0.05 for + vs ++). However, overexpression of cyclin Dl was not associated with a shortened overall survival of patients with invasive tumours (P< 0.1). These results suggest that genetic alteration of cyclin Dl appears to be an early event in the tumorigenesis of bladder TCC and is associated with early recurrence in superficial tumours.

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Section: Discussionsupporting

confidence: 51%

Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

Shin

Kong²,

Kim³

et al. 1997

Br J Cancer

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“…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).…”

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confidence: 99%

“…FADD protein expression was independent of lymph node metastasis and patients with both high FADD protein expression and lymph node metastasis had the worst prognosis for survival (Gibcus et al, 2007b). However, although FADD is a prognostic marker for increased mortality, we can not exclude that other genes within the 11q13 region are (also) involved.The most frequently studied genes within the 11q13.3 region are cyclin D1 and cortactin (Schuuring, 1995). 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).…”

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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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“…Cortactin also colocalises with F-actin in invadopodia of metastatic tumour cells, where it participates in degradation of the extracellular matrix around tumours (Artym et al, 2006;Yamaguchi et al, 2006). The cortactin gene CTTN (formerly EMS1) resides on chromosome locus 11q13 that is frequently amplified in human cancers, including over 30% HNSCCs (Brookes et al, 1993;Schuuring, 1995;Huang et al, 2006;Gibcus et al, 2007). Thus, the functional properties of cortactin, together with amplification of chromosome locus 11q13, suggest a link between its overexpression and tumour invasion and/or metastasis.…”

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Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

et al. 2008

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Cortactin is an actin-binding Src substrate involved in cell motility and invasion. In this study, we sought to examine the prognostic importance of cortactin protein expression in head and neck squamous cell carcinoma (HNSCC). To do so, cortactin and EGF receptor (EGFR) expression was retrospectively evaluated by immunohistochemistry in a tissue microarray composed of 176 HNSCCs with a mean follow-up time of 5 years. Cortactin immunoreactivity was weak to absent in normal epithelial tissue. Overexpression of the protein in 77 out of 176 tumours (44%) was associated with more advanced tumour-node-metastasis stage and higher histologic grade. Cortactin overexpression was associated with significantly increased local recurrence rates (49 vs 28% for high and low expressing carcinomas, respectively), decreased disease-free survival (17 vs 61%), and decreased the 5-year overall survival of (21 vs 58%), independently of the EGFR status. In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Importantly, we identified a subset of patients with cortactin-overexpressing tumours that displayed low EGFR levels and a survival rate that equalled that of patients with tumoral overexpression of both EGFR and cortactin. These findings identify cortactin as a relevant prognostic marker and may have implications for targeted therapies in patients with HNSCC.

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The involvement of the chromosome 11q13 region in human malignancies: Cyclin D1 and EMS1 are two new candidate oncogenes-a review

Cited by 242 publications

References 88 publications

Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

Cortactin expression predicts poor survival in laryngeal carcinoma

Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

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