The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, andmdr gene expression in colorectal cancer

Mayer, Astrid; Takimoto, Masafumi; Fritz, Elke; Schellander, Georgine; Kofler, Klaus; Ludwig, Heinz

doi:10.1002/1097-0142(19930415)71:8<2454::aid-cncr2820710805>3.0.co;2-2

Cited by 380 publications

(182 citation statements)

References 22 publications

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“…The mechanisms underlying the role of EGFR in colorectal cancer are not entirely clear. EGFR is overexpressed in up to 82% of colorectal cancers [6][7][8][9][10]. EGFR amplification, preferentially of a mutant allele, is correlated with but does not reliably predict EGFR overexpression [17].…”

Section: Egfr and Colorectal Cancermentioning

confidence: 99%

“…Patients with colorectal carcinomas showing EGFR staining by immunohistochemistry (IHC) in >50% of tumor cells have a poor prognosis [8]. High EGFR expression correlates with lower response rates in patients with advanced rectal cancer undergoing preoperative radiotherapy [31].…”

Section: Egfr and Colorectal Cancermentioning

confidence: 99%

“…The majority of patients with colorectal cancer are diagnosed with locally advanced or metastatic disease which responds poorly to conventional forms of treatment. The drugs recently introduced for treating colorectal cancer target the EGFR, which is overexpressed in 50-80% of colorectal tumors [6][7][8][9][10]. Although the advent of EGFR-targeted therapies has improved outcomes for colorectal cancer patients, they are effective in only a subset of patients [11].…”

Section: Introductionmentioning

confidence: 99%

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KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

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Section: Egfr and Colorectal Cancermentioning

confidence: 99%

Section: Egfr and Colorectal Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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“…High proliferative activity has been shown to correlate with poor clinical outcome in a variety of human malignancies such as breast cancer (Tubiana et al, 1989;Gasparini et al, 1992a;Aaltomaa et al, 1993;Siitonen et al, 1993;Railo et al, 1993;Haerslev and Jacobsen, 1994), colon cancer (Alsheneber et al, 1993;Mayer et al, 1993), lung cancer (Fujii et al, 1993), bladder cancer (Skopelitou et al, 1992;Lipponen et al, 1992;Mulder et al, 1992), prostatic cancer (Harper et al, 1992) or ovarian cancer (Isola et al, 1990;Jordan et al, 1993;Kerns et al, 1994;Henriksen et al, 1994;Thomas et al, 1995). Nevertheless, studies lacking such a correlation between tumour cell proliferation and prognosis have also been reported in the same tumour entities (Hemming et al, 1992;Kubota et al, 1992;Gasparini et al, 1992b;Cummings et al, 1993;Thomas et al, 1993).…”

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confidence: 99%

Immunohistochemical study on the prognostic value of MIB-1 in gastric carcinoma

Müller

Schneiders²,

Meier³

et al. 1996

Br J Cancer

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Summary The prognostic significance of tumour cell proliferation was investigated in a series of 418 gastric carcinomas using the monoclonal antibody MIB-1. Owing to strong intratumoural heterogeneity of MIB-1 expression three different proliferation indices (PIs) were determined in all carcinomas: (1) PImax in areas of maximal tumour cell proliferation, (2) PIrand in areas randomly distributed over the whole tumour, (3) Plfront in areas exclusively located at the tumour invasion front. There was a strong intertumoral heterogeneity with

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“…Expression of the epidermal growth factor receptor (EGFR) has been associated with outcome in colon cancer (Mayer et al, 1993;Saloman et al, 1995). Gefitinib is an oral EGFR tyrosine kinase inhibitor with an excellent safety profile.…”

mentioning

confidence: 99%

A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer

et al. 2005

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Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive growth inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study to determine the tolerability and efficacy of gefitinib in combination with irinotecan, infusional 5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13 patients with advanced colorectal cancer, 10 required dose reductions of irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of whom required hospitalisation, three with neutropenic fever. One patient achieved partial response and seven had disease stabilisation. The combination of this standard chemotherapy regimen with gefitinib is associated with excessive toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic level.

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The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, andmdr gene expression in colorectal cancer

Cited by 380 publications

References 22 publications

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

Immunohistochemical study on the prognostic value of MIB-1 in gastric carcinoma

A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer

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