Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

Morrison, Larry E.; Jacobson, Kristine; Friedman, Michael; Schroeder, James W.; Coon, John S.

doi:10.1097/01.mlg.0000163755.21035.8f

Cited by 25 publications

(23 citation statements)

References 13 publications

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“…Although, the rate limiting polysomy number of biological significance is not known, our analysis of categorical groupings showed that even low levels of chromosomal duplication affected rate of progression to death (Table 2, Figure 3). Similar to other carcinomas, polysomy/EGFR copy number in our study correlated with poor prognosis suggesting DNA aneuploidy and/or relative increase in EGFR copy number plays an adverse biological role (14, 24, 26-28). Interestingly, previous reports have shown that response to cetuximab and panitumumab, two epidermal growth factor inhibitors (tyrosine kinase inhibitors) correlated with EGFR copy number (polysomy and amplification) in colonic adenocarcinoma (25) and not mutational status.…”

Section: Discussionsupporting

confidence: 83%

Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

Williams

Roberts

Kies

et al. 2010

Clinical Cancer Research

126

100

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Purpose Salivary duct carcinoma over-expresses epidermal growth factor receptor (EGFR) and HER-2 though underlying mechanisms remain undefined. Because of potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value. Experimental Design A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquanititively evaluated into a 3-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of Exons 18, 19 and 21 of the EGFR gene for mutations was performed. Results EGFR Forty-six (69.7%) of the 66 tumors showed some form of EGFR expression (17,3+; 17,2+; 12,1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (3) and exon 19 (2). Polysomy of chromosome 7(average >2.5 copies per cell) was detected in 15 (25.0%) of 60 tumors (6,3+; 5,2+; 2,1+; 2,0+ expression) and correlated with poor 3-year survival (p=0.015). HER-2: Seventeen (25.8%) of 66 tumors expressed HER-2 (10,3+; 3,2+; 4,1+). Eight tumors showed HER-2 gene amplification (6,3+; 1,1+; 1,0+ protein expression). Chromosome 17 polysomy was found in eight (15.7%) of 51 tumors; two with HER-2 expression (3+; 1+). Conclusion Our study shows that salivary duct carcinomas: 1) harbor EGFR gene mutations in a subset of tumors which may guide therapy, 2) pursue aggressive clinical course in cases with Chromosome 7 polysomy and high EGFR expression, and 3) with HER-2 gene amplification and protein high-expression maybe selected for targeted therapy.

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Section: Discussionsupporting

confidence: 83%

Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

Williams

Roberts

Kies

et al. 2010

Clinical Cancer Research

126

100

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“…The involvement of EGFR signaling has been demonstrated in various cellular processes ranging from normal growth and differentiation to oncogenesis (40)(41)(42). Aberrant EGFR as a result of receptor mutation and/or overexpression occurs in NSCLC (43) laryngeal cancer (44), pancreatic cancer (45). Our previous study indicated that EGFR activation promotes HNSCC cell migration and invasion by inducing an EMT-like phenotypic change and MMP-9-mediated degradation of E-cadherin into soluble E-cadherin (sE-cad) associated with activation of ERK-1/2 and PI3K signaling pathways (25).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CXCR4 promotes invasion and migration of non‑small cell lung cancer via EGFR and MMP‑9

Zuo

Wen

et al. 2017

Oncol Lett

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Abstract. The aim of the present study was to verify whether overexpression of CXC receptor 4 (CXCR4) promotes the invasion and migration of non-small cell lung cancer (NSCLC) via epidermal growth factor receptor (EGFR) and matrix metallopeptidase-9 (MMP-9), and to detect the association between CXCR4, EGFR and MMP-9. The effects of overexpression of CXCR4 on lung cancer cell functions were investigated by migration and invasion assays. Western blotting and zymograph assays were used to analyze the protein expression levels of EGFR and the production of MMP-9, respectively. Immunohistochemistry was applied to analyze the expression of EGFR, CXCR4 and MMP-9 in NSCLC. Statistical analyses were used to detect the associations among EGFR, CXCR4 and MMP-9 in NSCLC. Finally, survival analyses were performed. CXCR4 overexpression enhanced cell motility and invasion. CXCR4 also promoted expression of EGFR and elevated MMP-9 production. CXCR4, EGFR and MMP-9 were highly expressed in NSCLC, and were not identified as associated with age and sex (P>0.05). However, they were associated with tumor differentiation and lymph node metastasis (P<0.05). CXCR4, EGFR and CXCR4 expression were positively associated with one another in NSCLC (P<0.05). In addition, patients with positive expression of CXCR4, EGFR or MMP-9 in tumors exhibited significantly shorter overall survival compared with those with negative expression (P<0.05). In conclusion, CXCR4 overexpression enhanced cell motility and invasion via EGFR and MMP-9. CXCR4, EGFR and MMP-9 were identified as highly expressed in NSCLC, and there was positive correlation among them.

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“…¼ not available. 7 This dysplastic lesion contained one part with small nuclei, punctated HPV and chromosome disomy and another part with large nuclei, granular HPV and polysomic chromosome numbers.…”

Section: Hpv16-positivity and Chromosome Stability Are Associated Witmentioning

confidence: 99%

“…[4][5][6] We and others have shown that alterations in chromosome 1 and 7 copy numbers detected by FISH are frequently found in head and neck (pre)malignancies. 7,8 On the basis of imbalances in chromosome 1 and 7 copy number ratios, we were able to reliably predict malignant progression and tumor recurrence. [8][9][10] In these cases, the chromosome 1 copy number most often equalled the average copy number of all chromosomes (ploidy) in the lesions, whereas generally higher copy numbers for chromosome 7 were detected.…”

mentioning

confidence: 99%

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

Mooren

Kremer

Claessen

et al. 2012

Intl Journal of Cancer

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Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV) and chromosome instability. Data from cellular model systems are, however, controversial concerning a relation between HPV and chromosome instability development. Here we studied this association in 77 primary TSCC with known clinical outcome and cell cycle protein expression profiles. Thirty‐two tumors (42%) showed HPV16‐integration. All 77 cases were analyzed by fluorescence in situ hybridization using chromosome 1‐ and 7‐specific centromere DNA probes to detect chromosome instability, indicated by the presence of chromosome imbalances and/or polyploidization for these chromosomes. In addition, eight HPV‐positive dysplasias, seven of which were adjacent to a carcinoma, were analyzed. Disomy for chromosome 1 and 7 was present in 29 out of 77 TSCC (38%), of which 19 were HPV16‐positive (p = 0.002). Aneusomy was observed in the remaining 48 TSCC, of which 13 were HPV‐positive. Aneusomies correlated significantly with tobacco‐ and alcohol consumption (p = 0.001 and p = 0.016, respectively) and a higher T‐stage (p = 0.018). Both HPV‐positivity and chromosome disomy were significantly associated with a favorable disease‐free survival (p = 0.001 and p = 0.025, respectively). Particularly in the HPV16‐positive group chromosome instability is a very strong indicator for an unfavorable prognosis (p = 0.032). In the dysplasias an identical HPV and chromosome copy number status was identified as in the adjacent tumors. We conclude that HPV‐positive TSCC and their precursor lesions are more often genetically stable than HPV‐negative lesions and that these tumors are associated with a favorable prognosis. Chromosome instability is an indicator for unfavorable prognosis, particularly in the HPV‐positive patient group.

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Aberrant EGFR and Chromosome 7 Associate with Outcome in Laryngeal Cancer

Abstract: Measurements of EGFR and chromosome 7 FISH status, and to a lesser extent EGFR expression, have potential value in treatment planning for patients with laryngeal SCC.

Cited by 25 publications

References 13 publications

Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

Overexpression of CXCR4 promotes invasion and migration of non‑small cell lung cancer via EGFR and MMP‑9

Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis

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