EMS1 gene amplification correlates with poor prognosis in HNSCC

Rodrigo, Juan P.; Garcı́a, Luis; Lazo, Pedro S.; Ramos, Sofı́a; Suarez, Carlos J.

doi:10.1016/s0194-5998(99)80108-9

Cited by 92 publications

(141 citation statements)

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“…Amplification of the CTTN gene has been linked to poor prognosis in HNSCC (Rodrigo et al, 2000), yet the relationship between cortactin protein levels and prognosis has not been thoroughly investigated to date. Tissue microarrays have previously been shown to represent reliable tools for the identification of cellular and molecular alterations in several tumour types, including HNSCCs (Gomaa et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…In the poor survival subgroup, we also observed at chromosome 11q13 two areas of gain marked by CCND1, FGF3, and EMS1 genes. Interestingly, all these genes have been associated with different tumors; [16][17][18] in particular, EMS1 amplification and overexpression was related to poor prognosis in breast cancer 19 and disease progression in esophageal squamous cell carcinoma. 20 A DNA gain at chromosome 20q is the most frequent chromosomal aberration described in esophageal adenocarcinoma, being found in up to 60% of cases.…”

Section: Discussionmentioning

confidence: 99%

“…However, when the total number of chromosomal imbalances was correlated to patient survival, a significant association (P ¼ 0.002) between the total number of gains/losses and survival was found. In particular, by dividing the patients according to their median survival time (20 months), we found that the mean number of quantitatively altered genes per tumor was 20.7 (range 6-33) in patients with a survival r20 months (17 patients), compared to 10.1 (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] in patients with a survival 420 months (16 patients) ( Table 2). Similarly, stratification of the patients according to the median number of chromosomal imbalances (12 aberrations), showed a good association with survival (P ¼ 0.014).…”

Section: Association Between Copy Number Alterations and Survival In mentioning

confidence: 99%

DNA copy number alterations correlate with survival of esophageal adenocarcinoma patients

et al. 2009

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Despite recent advances in surgical and multidisciplinary treatment, prognosis for patients with esophageal adenocarcinoma remains poor, and the low prognostic significance of pTNM staging suggests that additional parameters are needed. To identify genomic abnormalities characteristic of esophageal adenocarcinoma, a panel of 33 samples obtained at surgery from previously untreated patients were analyzed by muliplex ligationdependent probe amplification technique. We detected frequent gains of 6p, 8q, 13q, 17q, 20q, and losses of 4q, 5q, 15q, and 18q. When DNA copy number changes were correlated to clinicopathological features of patients no association was found between the number of chromosomal aberrations and gender, age, tumor grade or pTNM staging. However, interestingly, a significant correlation between patient survival and total number of chromosomal aberrations was found when esophageal adenocarcinoma cases were stratified according to the median of survival (20 months) (P ¼ 0.002) or the median of aberrations (12 aberrations) (P ¼ 0.014). Evaluation of the distribution of gains and losses at the level of single chromosomes indicated that gains on chromosomes 5, 6, 8, 11, 20 and losses on chromosomes 1, 3, 5, 11, and 18 were significantly different in the two survival groups. Furthermore, when single gene imbalances were analyzed in further details, we found that besides alterations that involve genes shared by both survival groups, a few genes (KIAA0170, EMS1, ABCC4, F3, and MIF) were altered only in samples from patients with poor survival. Thus, we established a good correlation between the total number of chromosomal alterations and survival, suggesting that the estimation of total imbalances might represent an additional indicator of disease outcome. In addition, the finding of alterations specific for the more aggressive esophageal adenocarcinoma subset might represent promising biomarkers to increase the accuracy of clinical outcome prediction.

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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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EMS1 gene amplification correlates with poor prognosis in HNSCC

Cited by 92 publications

References 0 publications

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

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

DNA copy number alterations correlate with survival of esophageal adenocarcinoma patients

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

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