Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases

McKay, Judith; Murray, L.; Curran, Stephanie; Ross, Val G.; Clark, Caroline; Murray, Graeme I.; Cassidy, Jim; McLeod, Howard L.

doi:10.1016/s0959-8049(02)00234-4

Cited by 199 publications

(140 citation statements)

References 20 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…However, EGFR mRNA and peptide expression appeared to be not associated with the CA-SSR Ⅰ allele length, nor with the presence of MSI or AI. Our data regarding EGFR peptide expression are in accordance with those obtained by McKay et al [26] who showed no association between the distribution of CA-SSR Ⅰ alleles in colorectal tumors and EGFR peptide expression. More intriguingly, the CA-SSR Ⅰ genotype identified in normal colon samples was not predictive of EGFR mRNA expression levels.…”

Section: B Asupporting

confidence: 93%

Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-defi cient colorectal cancers

Buisine¹,

Wacrenier²,

Mariette³

et al. 2008

WJG

View full text Add to dashboard Cite

SSR Ⅰ genotype on the expression of the EGFR gene was evaluated in 18 specimens using quantitative real-time reverse transcription PCR and immunohistochemistry. RESULTS:Mutations in CA-SSR Ⅰ were detected in 86% (36 of 42) of MSI-H colorectal tumors and 0% (0 of 44) of MSS tumors, indicating the EGFR gene as a novel putative specific target of the defective MMR system (P < 0.001). Impaired expression of EGFR was detected in most of the colorectal tumors analyzed [6/12 (50%) at the mRNA level and 15/18 (83%) at the peptide level]. However, no association was apparent between EGFR expression and CA-SSR Ⅰ status in tumors or normal tissues. CONCLUSION:Our results suggest that CA-SSRⅠ sequence does not contribute to the regulation of EGFR transcription in colon, and should thus not be considered as a promising predictive marker for response to EGFR inhibitors in patients with colorectal cancer. INTRODUCTIONThe epidermal growth factor receptor EGFR (HER1/ ERBB1) is a member of the erbB family. It plays a pivotal role in the control of processes occurring during oncogenesis and tumor progression, such as cell survival, proliferation,

show abstract

Section: B Asupporting

confidence: 93%

Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-defi cient colorectal cancers

Buisine¹,

Wacrenier²,

Mariette³

et al. 2008

WJG

View full text Add to dashboard Cite

show abstract

“…(iii) the existence of different molecular patterns between primary tumour and paired metastatic lesion as predictive markers, so far, have been mostly evaluated in primary tumours disregarding alterations at metastatic sites. To shed light into this latter issue, earlier studies investigating primary tumours and paired metastases by IHC revealed different patterns of EGFR expression (McKay et al, 2002;Ooi et al, 2004;Scartozzi et al, 2004;Bralet et al, 2005;Italiano et al, 2005;Bibeau et al, 2006;Cappuzzo et al, 2007). Our data show that all primary tumours and metastases were positive, although they showed different staining intensities (data not shown).…”

Section: B Dsupporting

confidence: 53%

“…It is possible, however, that primary tumour and paired metastatic lesions might be different at the molecular marker expression or gene status levels and that these differences may affect the clinical significance of a predictive test. In this contest, it is noteworthy that the few previously published studies on this issue focused almost exclusively on the rather unreliable evaluation of EGFR expression by IHC (McKay et al, 2002;Ooi et al, 2004;Scartozzi et al, 2004;Bralet et al, 2005;Italiano et al, 2005;Bibeau et al, 2006;Cappuzzo et al, 2007). The aim of this study is to analyse molecular alterations predictive for anti-EGFR therapies response, such as EGFR gene status, K-Ras and BRAF mutations, and PTEN protein expression, in primary tumour and synchronous or metachronous metastasis.…”

mentioning

confidence: 99%

Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant

et al. 2009

View full text Add to dashboard Cite

Cetuximab and panitumumab efficacy in metastatic colorectal cancer (mCRC) may be influenced by EGFR gene status and/or deregulation of its downstream signalling proteins detected in primary tumour. However, metastasis might have different molecular patterns with respect to primary tumour, possibly affecting the prediction of EGFR-targeted therapy efficacy. We analysed primary tumour and metastasis in 38 mCRC patients. Twelve cases were cetuximab/panitumumab treated. EGFR gene status and protein expression were investigated through fluorescent in situ hybridisation and immunohistochemistry (IHC), K-Ras/BRAF mutations by sequencing and PTEN expression by IHC. We observed EGFR gene deregulation in 25 out of 36 primary tumours and 29 out of 36 metastases, K-Ras mutations in 16 out of 37 cancers and in 15 out of 37 metastases, BRAF mutations in 2 out of 36 cancers and 2 out of 36 metastases and PTEN loss in 8 out of 38 cancers and 12 out of 38 metastases. For the first time in literature, we show that primary colorectal cancer and paired metastasis may exhibit difference with respect to EGFR pathway deregulation mechanisms possibly implying a different response to cetuximab or panitumumab treatment. The investigation of treated patients confirms this hypothesis. We therefore suggest that the analysis of metastatic lesion should be considered in patient management as well as in designing future clinical trials aimed to investigate the effect of anti-EGFR monoclonal antibodies in the treatment of mCRC.

show abstract

“…The expression of EGFR was present in 71% of cases, which is similar to the rate of expression observed in colorectal cancer. As in colorectal cancer, the expression level of EGFR was not associated with changes in survival (McKay et al, 2002). Although limited numbers of patients have been tested, it seems that activating mutations in the KRAS oncogene are observed in approximately 40% of SBA patients, which is similar to the rate observed in colorectal cancer (Bamford et al, 2004).…”

Section: Discussionmentioning

confidence: 65%

Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Despite having a dramatically larger surface area than the large intestine, the small intestine is an infrequent site for the development of adenocarcinoma. To better understand the molecular abnormalities in small bowel adenocarcinoma (SBA), we characterised a number of candidate oncogenic pathways and the immunophenotype of this rare cancer. METHODS: Tissue microarrays were constructed from tumour samples from 54 patients with all stages of the disease. Immunohistochemistry and microsatellite instability (MSI) testing were conducted. RESULTS: The profile of cytokeratin 20 and 7 coexpression was variable, but expression of caudal type homeobox transcription factor 2 (CDX2) was present in 70% of cases. In this young population (median age 54 years), loss of mismatch repair (MMR) proteins occurred in 35% of patients, with confirmed MSI in 100% of tested cases. Expression of vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor receptor (EGFR) was common, occurring in 96 and 71% of patients, respectively. Only one case showed HER2 expression and none showed loss of phosphatase and tensin homologue mutated on chromosome 10 (PTEN). CONCLUSIONS: These results suggest that alterations in DNA MMR pathways are common in SBAs, similar to what is observed in large bowel adenocarcinomas. Furthermore, the high percentage of tumours expressing both EGFR and VEGF suggests that patients with this rare cancer may benefit from therapeutic strategies targeting EGFR and VEGF receptor (VEGFR).

show abstract

Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases

Cited by 199 publications

References 20 publications

Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-defi cient colorectal cancers

Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-defi cient colorectal cancers

Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant

Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine

Contact Info

Product

Resources

About