Prognostic significance of EGF receptor expression in early glottic cancer

Abstract

Objective: A positive relationship between epidermal growth factor receptor (EGFR) expression and radioresistance has been shown both in vitro and in vivo. In a group of 31 patients with early glottic cancer treated with definitive radiotherapy, the relationship of EGFR expression with patient and tumor related parameters were analyzed and the prognostic effect of EGFR expression on local control (LC) was assessed.

Material and method: Between 1991 and 2001, 114 patients with early glottic (Tis-T2N0M0) squamous cell carcinoma were treated with radiotherapy at our institution. Among these, 31 patients whose pretreatment pathology specimens were available for immunohistochemical analysis formed the study population. Median age was 64 (46-77). Anterior commissure involvement was evident in 12 (38.7%) patients. Distribution according to T stage was as follows: Tis 6 (19.3%), T1 22 (71%), and T2 3 (9.7%). Histopathological grades of the 25 T1-2 tumors were 10/25 (40%) grade 1, 9/25 (36%) grade 2 and 6/25 (24%) grade 3. Our radiotherapy regimen was 66-70 Gy in 33-35 fractions over 6.5-7 weeks. The median follow-up period was 45 months (range, 5-116). Following immunohistochemical staining, quantitative immunohistochemistry (IHC) was performed by image analysis software and stained tumoral area percentage (STAP) was identified. The cut-off value was < or =5% versus >5%. The relationship of EGFR expression with patient (age) and tumor related (T stage, histopathological grade, and anterior commissure involvement) parameters was evaluated using chi-square test. Prognostic significance of EGFR expression, age, T stage, histopathological grade, and anterior commissure involvement on LC was assessed using log-rank test.

Results: No difference was found in EGFR content distribution in relation to age, T stage, histopathological grade, and anterior commissure involvement. In the univariate analysis including age (< or =60 versus >60), T stage (Tis and T1 versus T2), histopathological grade (grade 1 and 2 versus grade 3), anterior commissure involvement (present versus absent), and EGFR expression (high versus low), only T stage and EGFR expression were found to be significant prognostic factors affecting LC (P = 0.0006 and P = 0.03, respectively).

Conclusion: The results of this series support that EGFR expression is an unfavorable prognostic factor in early glottic carcinomas. For this reason EGFR IHC may be considered for selecting patients for more aggressive therapies (radiotherapy with different fractionation schemes or surgery) or enrollment into trials targeting EGFR signaling pathways.