Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with stage II and stage III colon carcinoma - A role for the host response in prognosis

BACKGROUND. The elucidation of new therapeutic targets of prognostic significance in colon carcinoma is necessary to improve outcomes. In the current study, the authors examined the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in primary colon carcinoma cases and VEGF in tumor-associated macrophages (TAM)/stroma, and their correlation with survival. METHODS. The authors identified 131 consecutive American Joint Committee on Cancer Stage II and Stage III colon carcinoma patients seen at the University of Rochester between 1990-1995. Expression of VEGF, EGFR, and CD68 were examined by immunohistochemistry in paraffin-embedded primary colon tumors and graded as the percentage of cells stained. Data were analyzed using a multivariate Cox proportional hazards model. RESULTS. VEGF expression in tumor was not found to be significantly associated with survival. However, 42% of the patients expressed VEGF in TAM/stroma. The median survival in this group was 9.7 years versus 4.3 years in the VEGF-negative (TAM/stroma) group (hazards ratio of 0.57, 95% confidence interval [95% CII, 0.34-0.95; P = 0.03). Although TAM infiltration alone was not found to be significant in multivariate analysis, the presence of both CD68 and VEGF (TAM/stroma) was predictive of improved survival (hazards ratio of 0.48, 95% Cl, 0.28-0.83; P = 0.006). High grades of EGFR expression (greater than or equal to Grade 2) were found to be associated with a trend toward worsened survival. CONCLUSIONS. The greater than twofold increase in median survival associated with VEGF-expressing TAM suggests a hitherto unknown role for this subset of cells in the host response to colon carcinoma and requires further investigation. Overexpression of EGFR may be associated with worsened survival, providing a rationale for trials of anti-EGFR agents as adjuvant therapy.