Expression and prognostic value of epidermal growth factor receptor, transforming growth factor-?, and c-erb B-2 in nephroblastoma

Ghanem, Mazen A.; Kwast, Theodorus H. van der; Hollander, Jan C. den; Sudaryo, Mondastri Korib; Mathoera, Rejiv B.; Heuvel, Marry M. van den; Noordzij, Marinus A.; Nijman, Rien J.M.; Steenbrugge, G.J. van

doi:10.1002/1097-0142(20011215)92:12<3120::aid-cncr10173>3.0.co;2-2

Cited by 44 publications

(30 citation statements)

References 37 publications

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“…According to our results, we reported that Her/2 expression was not significantly affect the outcome of our patients (p = 0.72 & p = 0.8 for OS and DFS respectively. This is in agree with the results reported by Ghanem et al [3] who suggested that c-erb B2 of no prognostic impact on the clinical outcome of patients and may not play a vital role in the aggressive behavior of WT in a similar study set of patients (previously treated with chemotherapy). In contrast, Salem et al [16] suggested that an over-expression of Her/2 might be associated with a perfect prognosis in WT; (however, it was difficult to conclude that due to few number of cases under study) and Ragab et al [17] who reported a good impact of Her/2 on overall and recurrence free survival of their patients.…”

Section: Discussionsupporting

confidence: 93%

“…In contrast, Salem et al [16] suggested that an over-expression of Her/2 might be associated with a perfect prognosis in WT; (however, it was difficult to conclude that due to few number of cases under study) and Ragab et al [17] who reported a good impact of Her/2 on overall and recurrence free survival of their patients. And before jumping to explain this controversy in the results by the [3] to chemotherapy, we found that the expression pattern of Her/2 among both groups (previously treated vs. previously non treated samples) was similar as mentioned earlier in this report. Also, in an additional study of a set of patients getting no chemotherapy before surgery by Ghanem et al [3] Similar results were gained which made him suggests that chemotherapeutic treatment didn't significantly affect the predictive value of the studied markers.…”

Section: Discussionsupporting

confidence: 80%

“…The biologic behavior of WT is difficult to prognosticate on the basis of histopathology findings only [3]. Although the last two decades had carried progress in the Her/2 proto-oncogene regarding tumor biology to an extent that Yokoi et al [31] suggested that cerbB-2 in an in vivo model may serve as a therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

“…A multidisciplinary approach in keeping with rules of National Wilms' Tumor Study Group (NWTSG) and International Society of Pediatric Oncology (SIOP) for the treatment of WT has considerably contributed to those results. However, WT is known for its unpredictable tendency of recurrence or metastasizing, sometimes years after primary treatment [3]. The most important predictors of treatment insufficiency for children with WT are tumor histology and stage of disease, each of that are used to stratify patients for appropriate modern therapeutic protocols [4] [5].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Impact of HER/2 Expression on Survival of Preoperatively Treated Children with Wilms Tumor at South Egypt

Sayed¹,

Refaiy²,

Salem³

2017

JCT

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Aim: Wilms tumor (WT) is the most frequent type of pediatric renal tumors. Her/2 is an oncoprotein, its over-expression revealed to play a very vital role in the progress and improvement of certain tumors. This study evaluates the possible role of Her/2 as a prognostic indicator in formerly treated WT. Method: Immunohistochemical expression of Her/2 was studied in paraffin material of 40 WT patients followed SIOP 9 protocol. Patients' medical records reviewed for clinical, pathological and outcome data and correlated with HER2 expression. Additional 15 samples of normal surrounding kidney tissue specimens were included. Results: Her/2 was often expressed in normal kidney tissue (renal tubules but not glomeruli) and at variable levels in the three elements of WT. At a median of 84 months, 70% of patients are living and under follow-up, surgical stage and pathologic subtypes were the only two factors significantly affect the outcome of our patients (p = 0.000, p = 0.007 & p = 0.004, p = 0.005 for OS (Overall survival) and DFS (Disease Free survival) respectively). Her/2 expression was associated with epithelial differentiation (p < 0.001). There was non-significant effect of Her/2 expression on OS or DFS of studied group. Conclusion: while the major progress in studying biology of WT, stage and pathological subtype continues the only predictive factors of significant value affecting the outcome of patients with WT. There was important association between Her/2 expression and histological differentiation in formerly treated Wilms tumor. Non-conclusive results regarding influence of Her/2 expression on the result of WT patients were found.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic Impact of HER/2 Expression on Survival of Preoperatively Treated Children with Wilms Tumor at South Egypt

Sayed¹,

Refaiy²,

Salem³

2017

JCT

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“…We have therefore hypothesized that GPCR-mediated EGFR activation might promote critical cancer cell characteristics such as tumour cell proliferation and motility. We were especially interested in EGFR signalling in urological malignancies because EGFR activity, which is indicative for the malignant potential of many solid cancers, is also elevated in this tumour type in comparison to normal tissue (Ghanem et al, 2001). High-grade, invasive bladder tumours often show genetic aberrations including overexpression of HER2/ neu and EGFR associated with an increased frequency of progression to an advanced tumour stage and poor survival.…”

Section: Discussionmentioning

confidence: 99%

Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion

2003

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Signalling through G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) is involved in the regulation of essential cellular processes and its deregulation is associated with tumorigenesis in vitro and in vivo. We investigated pathophysiological processes that are regulated by GPCR pathways in human kidney and bladder cancer cell lines. Our results show that GPCR ligands induce tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as well as downstream signalling events such as recruitment of the adapter protein Shc and activation of the mitogen-activated protein kinases (MAPK) ERK1/2, JNK and p38. Moreover, we report that the EGFR transactivation signal involves the EGFR ligands amphiregulin, HB-EGF and TGFa as well as the metalloproteinases ADAM 10, 15 and 17, depending on the cellular system. Finally, we demonstrate that EGFR transactivation is part of a regulatory system that modulates the migratory and invasive behaviour of kidney and bladder cancer cells. In conclusion, our findings demonstrate that metalloproteinase-mediated transactivation of the EGFR is a key mechanism of the cellular signalling network that promotes MAPK activation as well as tumour cell migration and invasion in response to a variety of physiologically relevant GPCR ligands, and therefore represents a novel target for cancer intervention strategies.

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Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors

Freeman

Allen

Ganti

et al. 2008

Cancer

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Background Osteosarcoma cell lines and tumors have been shown to express EGFR and harbor amplifications at the EGFR locus. In this study, we further analyze the genomic features of EGFR in osteosarcoma tumors and investigate whether they correlate with PTEN expression and copy number status. Methods EGFR and PTEN expression were assessed by immunohistochemistry (n=28), and copy number alterations at the EGFR and PTEN loci were surveyed using Affymetrix® 50K single nucleotide polymorphism (SNP) arrays (n=31) and fluorescence in situ hybridization (FISH) (n=27). The EGFR tyrosine kinase domain was sequenced to survey for activating mutations (n=34). In addition, we assessed EGFRvIII expression using RT-PCR (n=24). Results were correlated with available clinical information on 59 patients, with a median age of 14.1 years (range, 5–23 years) and median follow up of 4.4 years. Results EGFR expression was detected in the majority of osteosarcoma tumors surveyed (23/28; 82%). SNP arrays revealed evidence of frequent copy number gains at 7p11.2 and losses at 10q23.21. A sizeable subset (16/27 cases; 59%) showed gains at the EGFR locus using FISH – amplification in 4/27 (15%) and balanced chromosome 7 polysomy in 12/27 (44%), and 12 cases showed deletions at the PTEN locus – biallelic deletions in 4/27 (15%) and monoallelic deletion in 9/27 (33%). No activating mutations in the EGFR tyrosine kinase domain, EGFRvIII expression, or association with clinical findings were detected. Conclusion EGFR expression and genomic gains at the EGFR locus are prevalent in osteosarcoma tumors, which also commonly harbor deletions at the PTEN locus.

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Expression and prognostic value of epidermal growth factor receptor, transforming growth factor-?, and c-erb B-2 in nephroblastoma

Cited by 44 publications

References 37 publications

Prognostic Impact of HER/2 Expression on Survival of Preoperatively Treated Children with Wilms Tumor at South Egypt

Prognostic Impact of HER/2 Expression on Survival of Preoperatively Treated Children with Wilms Tumor at South Egypt

Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion

Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors

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