title: Increased epidermal growth factor receptor expression at the invasive margin is a negative prognostic factor in colorectal cancer.
abstract: The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is often expressed in solid malignant tumours, and the expression has been correlated to disease progression. Multiple new agents targeted against the EGFR have been developed during the last decade, but treatment selecting criteria are still not clear. This immunohistochemical study includes 386 colorectal cancer patients and focuses on EGFR expression variations within the tumour, comparing central parts to the invasive margin. Positive immunostaining for EGFR was evident in the central part in 176/386 (46%) of analyzed primary tumours. The invasive margin was positive in 222/386 (58%). A similar expression in both the central part and the invasive front was evident in 286/386 (74%). An increased score at the invasive margin compared to central parts (EGFR(i) ) was evident in 97/386 (25%) of the tumours. Moreover, the results show a significant survival disadvantage for the EGFR(i) group, both in potentially curatively resected colon cancer patients (n = 170, p = 0.01) and in potentially curatively resected colon and rectal cancer patients combined (n = 273, p = 0.013). Multivariate survival analysis adjusted for age, gender, bowel localisation, grade, stage and tumour type showed an increased risk of cancer death for EGFR(i) tumours (HR, 1.53; 95% CI, 1.04-2.23; p = 0.029). A significant correlation between EGFR expression at the invasive margin and the presence of budding was seen (p = 0.0001). This investigation of a large patient material implies that EGFR immunohistochemical analysis still has a role in risk evaluation of colorectal cancer patients.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. ingrid.ljuslinder@onkologi.umu.se
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ljuslinder
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
authors.forename: Maria L
authors.initials: ML
authors.lastname: Henriksson
authors.forename: Åke
authors.initials: Å
authors.lastname: Öberg
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors