Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer

Resnick, Murray B.; Routhier, Justin; Konkin, Tamako; Sabo, Edmond; Pricolo, Victor E.

doi:10.1158/1078-0432.ccr-03-0462

Cited by 183 publications

(141 citation statements)

References 39 publications

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“…As these two tests may yield a lower number of positive cases, one could argue that some of the negative cases of this report could have been positive if they were tested by Ventana 3C6 or the Zymed test used in our current study. Four antibodies were used in the recent studies of EGFR expression and according to our study, showed that they were not equivalent in terms of the percentage of positive cells (Table IV) (10)(11)(12)(13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 89%

Is there an immunohistochemical technique definitively valid in epidermal growth factor receptor assessment?

Penault‐Llorca¹,

Cayre²,

Arnould́³

et al. 2006

Oncol Rep

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Abstract. Immunohistochemistry (IHC) is required for the selection of patients for a monoclonal antibody based targeted treatment with C225 (Erbitux ® ). To validate the usefulness of IHC, the confirmation of assays and scoring systems are mandatory. In an attempt to standardize the immunohistochemical detection of the epidermal growth factor receptor (EGFR), we retrospectively evaluated three commercially available EGFR kits or antibodies and analyzed the discrepancies between the tests in terms of the percentage of positive cells, intensity, cut-off value and fixatives. We extracted 232 paraffin-embedded samples from a metastatic colorectal cancer clinical trial. For all the cases, EGFR expression was assessed with the FDA approved Dako EGFR pharmaDx kit, the Zymed EGFR kit and the Ventana EGFR 3C6 antibody. Different cut-off values were tested, and the intensity was scored 0, 1 + , 2 + , 3 + following Dako's recommendations. The percentage of positive cases varied from 93 to 75% with a cut-off of value 1% of positive cells, from 80 to 61% with a cut-off of 5% positive cells and from 72% to 48% with a cut-off value of 10%. Both Ventana and Zymed tests were more sensitive than the Dako test (Ventana >Dako; p<10 -7 , Zymed >Dako; p=2.10 -6 ). No difference was noted between Ventana and Zymed tests (p=0.75). A high concordance was observed for the 3 tests for the evaluation of high intensities. The use of a scoring system combining the percentage of positive cells and intensity was not useful for Zymed and Ventana as the intensity of staining is correlated to the percentage of positive cells: Ventana (p<10 -6 ) and . No interaction with staining was identified for any of the fixatives, or with the nature of samples received (i.e. slides vs blocks, biopsies vs surgical specimens). Our data showed a higher percentage of positive cells detected by Ventana and Zymed tests, whatever the cutoff value for positivity. No scoring system showed, to date, its accuracy, and more studies have to be conducted with an evaluation of the response to cetuximab, possibly with a correlation with FISH amplification in colorectal carcinoma.

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Section: Discussionmentioning

confidence: 89%

Is there an immunohistochemical technique definitively valid in epidermal growth factor receptor assessment?

Penault‐Llorca¹,

Cayre²,

Arnould́³

et al. 2006

Oncol Rep

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“…25,67 Furthermore, previous studies have provided evidence for the prognostic value of MET protein expression in the early stages of carcinoma progression. 68,69 In this study the majority of patients had metastatic disease and they all received the appropriate chemotherapy although their access to EGFR-or VEGF-targeted therapy was not always based on molecular biomarker selection; therefore, the data reported herein highlight the value of MET expression in metastases as a biomarker that might be used to select advanced colorectal cancer patients who could benefit from targeted therapies.…”

Section: Discussionmentioning

confidence: 95%

Combined analysis of KRAS and PIK3CA mutations, MET and PTEN expression in primary tumors and corresponding metastases in colorectal cancer

et al. 2013

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Metastasis is the main cause of mortality in patients with colorectal cancer. However, most of the targeted therapies and predictive molecular biomarkers were developed based mainly on primary tumors. The current study was conducted to determine the degree of discordance between potential predictive and/or prognostic molecular markers in primary colorectal tumors and corresponding metastases, as this could have an impact on the efficacy of targeted therapies in the advanced colorectal cancer. KRAS, PIK3CA and BRAF mutations were determined by Sanger sequencing and mutant-enriched polymerase chain reaction (PCR) assays in 83 paired samples, MET gene copy number by quantitative PCR in 59, MET expression by immunohistochemistry in 73 and nuclear and cytoplasmic expression of PTEN by immunohistochemistry in 78 and 71 pairs, respectively. A certain degree of discordance between primary tumors and corresponding metastases was demonstrated for all examined biomarkers except BRAF mutations. PIK3CA exon 9 mutations in primary tumors and loss of PTEN nuclear expression in metastases correlated with KRAS mutations. KRAS wild-type status in primary tumors was associated with loss of PTEN cytoplasmic expression and high gene copy number of MET. Survival and clinical data were available for 68 patients. The multiple regression analysis revealed that the right-sided tumor localization and overexpression of MET were associated with shorter overall survival.

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“…Although individuals at an early stage of colorectal cancer are excluded from adjuvant chemotherapy because tumor resection is potentially curative, 20% to 30% of such cases present recurrence of the disease. This suggests that the anatomopathological staging in itself is incapable of guaranteeing the patient's prognosis (24) . Therefore, investigation of molecular markers is important for evaluating the prognosis, and for allocating individuals to appropriate treatment protocols.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular markers may be the basis for decision-making of lower cost and greater precision, for prognoses and appropriate adjuvant therapies. Over recent years, the major focus within colorectal cancer research has been on searching for molecular markers that provide a prognosis and identify population types for specific treatment regimens (24) .…”

Section: Discussionmentioning

confidence: 99%

Analysis of the immunohistochemical expressions of p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and their correlations with the prognostic factors

Menezes

Júca

Gomes

et al. 2010

Arq. Gastroenterol.

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-Context -Search of tumors markers that allow treatment with higher survival rates, and indicate the response to treatment and recurrence of cancer -Objective -To analyze the immunoexpression of the proteins p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and correlate them with the clinical-pathological prognostic factors. Method -Tissue microarray paraffin blocks were made from colorectal adenocarcinoma tissue resected from 82 patients who had undergone surgery but not chemotherapy or radiotherapy, at "Hospital São Paulo", São Paulo, SP, Brazil, between 2002 and 2005. Thin sections (4 μm) were subjected to immunohistochemical reactions, and immunoexpression staining scores were obtained. The scores were correlated with the degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The study variables were analyzed using the chi-square and Kaplan-Meier tests to investigate associations with the markers. The significance of the differences between the curves of the diseasefree interval and survival was analyzed using the Logrank and Wilcoxon tests. Results -The immunohistochemical expression of p53 was positive in 70 tumors (85.4%) and negative in 12 (14.6%). The expression of bcl-2 was positive in 26 (31.7%) and negative in 56 (68.3%). The expression of Ki-67 was positive in 62 (75.6%) and negative in 20 (24.4%). There was no statistically significant correlation between the expressions of these markers separately or in conjunction, in relation to the degree of cell differentiation, staging, disease-free interval, survival and specific mortality. In relation to recurrence, there was a statistically significant correlation with positive expression of Ki-67 (P = 0.035). Conclusion -The immunohistochemical expression of Ki-67 in colorectal cancer is associated with recurrence of this disease. HEADINGS -Colorectal neoplasms. Adenocarcinoma. Immunohistochemistry. Tumor suppressor protein p53. Proto-oncogene proteins c-bcl-2. Bcl-2 homologous antagonist-killer protein.

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Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer

Cited by 183 publications

References 39 publications

Is there an immunohistochemical technique definitively valid in epidermal growth factor receptor assessment?

Is there an immunohistochemical technique definitively valid in epidermal growth factor receptor assessment?

Combined analysis of KRAS and PIK3CA mutations, MET and PTEN expression in primary tumors and corresponding metastases in colorectal cancer

Analysis of the immunohistochemical expressions of p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and their correlations with the prognostic factors

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