Epidermal growth factor receptor status predicts local response to radical radiotherapy in muscle-invasive bladder cancer.
OBJECTIVE
Epidermal growth factor receptor (EGFR) is expressed by over 70% of muscle-invasive bladder tumours and is associated with diminished overall survival. In model tumour systems, ionising radiation has been shown to activate EGFR, leading to cellular proliferation and is therefore a possible mechanism of underlying radioresistance. We carried out an immunohistochemical study relating the clinical outcome of patients receiving radical radiotherapy for muscle-invasive bladder cancer to tumour EGFR status.


METHODS
Archived paraffin-embedded tumours from 110 consecutive patients receiving radical radiotherapy for muscle-invasive bladder cancer between 1991 and 1997 were immunohistochemically stained for EGFR. Data were collected concerning the tumour stage and grade, the presence of ureteric obstruction, the response to radiotherapy at 3 months, local recurrence rates, metastatic spread and survival. Multivariate analysis of potential independent prognostic factors of impaired bladder cancer-specific survival was carried out using Cox's regression.


RESULTS
Of 110 tumours, 79 (72%) stained positively for EGFR. Of 87 patients undergoing the 3-month check cystoscopy, 60 (69%) had a positive response to radiotherapy. A positive response to radiotherapy correlated significantly with a negative EGFR status (chi(2) test, P = 0.05). Kaplan-Meier survival analysis revealed a trend towards improved bladder cancer-specific survival in EGFR-negative patients (Log-rank, P = 0.10). A lack of response to radiotherapy at 3 months, local recurrence, metastatic spread and the presence of ureteric obstruction were all independent prognostic factors for diminished bladder cancer-specific survival (Cox's regression: P = 0.009, P = 0.001, P = 0.04 and P = 0.005, respectively).


CONCLUSIONS
EGFR status predicts the local response to radiotherapy but does not provide prognostic utility in relation to overall or bladder cancer-specific survival. As EGFR status seems to be linked to the initial response to radiotherapy, its inhibition may be a means of enhancing the radio-responsiveness of these poor prognosis tumours. Colquhoun, A. J.
Colquhoun
A J
AJ
Department of Cancer Studies and Molecular Medicine, Clinical Sciences Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. ajc37@le.ac.uk
Sundar
S
S
Rajjayabun
P H
PH
Griffiths
T R L
TR
Symonds
R P
RP
Mellon
J K
JK
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000532:radiotherapy*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019042:Muscle Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000532:radiotherapy*
D014408:Biomarkers, Tumor; D066246:ErbB Receptors