Coexpression, prognostic significance and predictive value of EGFR, EGFRvIII and phosphorylated EGFR in colorectal cancer.
In colorectal cancer, epidermal growth factor receptor (EGFR) expression is reported in 8-100% of the cases examined and there has been no clear association between EGFR expression and prognosis, or response to EGFR inhibitors. In this retrospective study, 87 archival specimens from node positive (Dukes' C) colorectal cancer patients were analysed immunohistochemically, for the expression of EGFR, mutant EGFR (EGFRvIII) and phosphorylated EGFR (pEGFR, tyr1068). Each section was scored on the basis of location and intensity of staining, and the immunostaining was considered positive if greater than 10% of the tumour cells were stained by the antibody. The association between these scores and overall survival was estimated using univariate and multivariate (Cox) analysis. Overall, we found that 76% and 100% of cases were EGFR positive using antibodies to the external or internal domain of EGFR respectively, and 34% of the cases were EGFRvIII positive. However, only 8% of the cases expressed pEGFR and pEGFR immunostaining was never present in more than 10% of tumour cells. The expression of EGFR, EGFRvIII, pEGFR, or coexpression of EGFR and EGFRvIII was not associated with overall survival. Cytoplasmic expression of EGFR (p = 0.0141) or EGFRvIII (p = 0.005) was, however, associated with improved survival in patients receiving radiotherapy. Our results suggest that coexpression of cytoplasmic EGFR and EGFRvIII occurs in a significant proportion (34%) of Dukes' C colorectal cancer and the cytoplasmic expression of EGFR or EGFRvIII is a good indicator of response to radiotherapy.
Cunningham
Matthew P
MP
Division of Oncology, Postgraduate Medical School, Guildford, GU2 7XH, UK.
Essapen
Sharadah
S
Thomas
Hilary
H
Green
Margaret
M
Lovell
David P
DP
Topham
Clare
C
Marks
Christopher
C
Modjtahedi
Helmout
H
D000368:Aged; D000918:Antibody Specificity / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors