Role of Epidermal Growth Factor Receptor (EGFR) and HER2-neu Receptor Expression in Predicting Biochemical Failure after Radical Radiotherapy for Prostate Cancer

Abstract

Purpose/Objective(s)Both EGFR and HER2 new pathways have been implicated in prostate cancer growth. Increasing evidence indicates that the EGFR may play an important role in determining cellular response to radiotherapy and more specifically various pre-clinical and clinical studies suggest that EGFR overexpression may mediate radioresistance through activating its downstream signal pathway.Materials/MethodsEGFR and HER2 expression was evaluated by immunohistochemistry in 84 patients treated with radical radiotherapy in the Northern Centre for Cancer Treatment, in Newcastle in the UK between 1996 and 2000. Clinicopathological variables including age, Gleason score, stage, presenting PSA and radiotherapy dose were documented, as well as time to PSA / biochemical failure following radical RT. PSA failure was defined using the nadir PSA + 2 definition. The association of PSA failure and EGFR or HER2 expression was tested by the chi-square test.ResultsWith a cutoff point of 1% extent expression for EGFR, there was a statistically significant association between EGFR expression and PSA relapse as 3 out of 17 EGFR negative patients relapsed compared to 30/67 EGFR +ve patients (X2 = 4.18, p = 0.041). Regarding HER2-new intensity scoring (0 and +1 considered negative and +2 and +3 considered positive) there was also a statistically significant association between HER2 expression and PSA relapse, as 26 out of 74 HER2 -ve patients relapsed compared to 7 out of 10 HER2 +ve patients (X2 = 4.48, p = 0.034). Dual EGFR and HER2 +ve patients had 6 out of 8 patients relapsing compared to 2 out of 15 relapses for dual EGFR and HER2-ve patients (X2 = 8, p = 0.0136). There was also an association of presenting PSA and PSA failure (t test = 4.9, p = 0.000004), but no association was found between PSA failure with either stage or Gleason score. EGFR expression was not found to be associated with either PSA, stage or Gleason score, HER2 expression however was associated with high (8-10) Gleason score (x2 = 4.41, p = 0.0357).ConclusionsPatients with prostate cancer with overexpression of either or both EGFR and HER2 on immunohistochemistry have an increased risk of biochemical relapse after radical radiotherapy. Alternative strategies of either surgery or utilization of EGFR and HER2 inhibition combined with radiotherapy need to be considered for such patients. Purpose/Objective(s)Both EGFR and HER2 new pathways have been implicated in prostate cancer growth. Increasing evidence indicates that the EGFR may play an important role in determining cellular response to radiotherapy and more specifically various pre-clinical and clinical studies suggest that EGFR overexpression may mediate radioresistance through activating its downstream signal pathway. Both EGFR and HER2 new pathways have been implicated in prostate cancer growth. Increasing evidence indicates that the EGFR may play an important role in determining cellular response to radiotherapy and more specifically various pre-clinical and clinical studies suggest that EGFR overexpression may mediate radioresistance through activating its downstream signal pathway. Materials/MethodsEGFR and HER2 expression was evaluated by immunohistochemistry in 84 patients treated with radical radiotherapy in the Northern Centre for Cancer Treatment, in Newcastle in the UK between 1996 and 2000. Clinicopathological variables including age, Gleason score, stage, presenting PSA and radiotherapy dose were documented, as well as time to PSA / biochemical failure following radical RT. PSA failure was defined using the nadir PSA + 2 definition. The association of PSA failure and EGFR or HER2 expression was tested by the chi-square test. EGFR and HER2 expression was evaluated by immunohistochemistry in 84 patients treated with radical radiotherapy in the Northern Centre for Cancer Treatment, in Newcastle in the UK between 1996 and 2000. Clinicopathological variables including age, Gleason score, stage, presenting PSA and radiotherapy dose were documented, as well as time to PSA / biochemical failure following radical RT. PSA failure was defined using the nadir PSA + 2 definition. The association of PSA failure and EGFR or HER2 expression was tested by the chi-square test. ResultsWith a cutoff point of 1% extent expression for EGFR, there was a statistically significant association between EGFR expression and PSA relapse as 3 out of 17 EGFR negative patients relapsed compared to 30/67 EGFR +ve patients (X2 = 4.18, p = 0.041). Regarding HER2-new intensity scoring (0 and +1 considered negative and +2 and +3 considered positive) there was also a statistically significant association between HER2 expression and PSA relapse, as 26 out of 74 HER2 -ve patients relapsed compared to 7 out of 10 HER2 +ve patients (X2 = 4.48, p = 0.034). Dual EGFR and HER2 +ve patients had 6 out of 8 patients relapsing compared to 2 out of 15 relapses for dual EGFR and HER2-ve patients (X2 = 8, p = 0.0136). There was also an association of presenting PSA and PSA failure (t test = 4.9, p = 0.000004), but no association was found between PSA failure with either stage or Gleason score. EGFR expression was not found to be associated with either PSA, stage or Gleason score, HER2 expression however was associated with high (8-10) Gleason score (x2 = 4.41, p = 0.0357). With a cutoff point of 1% extent expression for EGFR, there was a statistically significant association between EGFR expression and PSA relapse as 3 out of 17 EGFR negative patients relapsed compared to 30/67 EGFR +ve patients (X2 = 4.18, p = 0.041). Regarding HER2-new intensity scoring (0 and +1 considered negative and +2 and +3 considered positive) there was also a statistically significant association between HER2 expression and PSA relapse, as 26 out of 74 HER2 -ve patients relapsed compared to 7 out of 10 HER2 +ve patients (X2 = 4.48, p = 0.034). Dual EGFR and HER2 +ve patients had 6 out of 8 patients relapsing compared to 2 out of 15 relapses for dual EGFR and HER2-ve patients (X2 = 8, p = 0.0136). There was also an association of presenting PSA and PSA failure (t test = 4.9, p = 0.000004), but no association was found between PSA failure with either stage or Gleason score. EGFR expression was not found to be associated with either PSA, stage or Gleason score, HER2 expression however was associated with high (8-10) Gleason score (x2 = 4.41, p = 0.0357). ConclusionsPatients with prostate cancer with overexpression of either or both EGFR and HER2 on immunohistochemistry have an increased risk of biochemical relapse after radical radiotherapy. Alternative strategies of either surgery or utilization of EGFR and HER2 inhibition combined with radiotherapy need to be considered for such patients. Patients with prostate cancer with overexpression of either or both EGFR and HER2 on immunohistochemistry have an increased risk of biochemical relapse after radical radiotherapy. Alternative strategies of either surgery or utilization of EGFR and HER2 inhibition combined with radiotherapy need to be considered for such patients.