The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer.
OBJECTIVE
The role of the type I receptor tyrosine kinase (HER) family in progression of prostate cancer is controversial. Breast cancer studies show that these receptors should be investigated as a family. The current study investigates expression of HER1-HER4 and EGFRvIII in matched hormone-sensitive and hormone-refractory prostate tumors.


METHODS
Immunohistochemical analysis was used to investigate protein expression of HER1-HER4, EGFRvIII, and phosphorylated Akt (pAkt) in matched hormone-sensitive and hormone-refractory prostate tumors.


RESULTS
Surprisingly, high HER2 membrane expression in hormone-sensitive tumors was associated with an increased time to biochemical relapse (P = 0.0003), and this translated into longer overall survival (P = 0.0021). Consistent with other studies, HER4 membrane expression in hormone-sensitive tumors was associated with longer time to biochemical relapse (P = 0.042), and EGFRvIII membrane expression was associated with shorter time to biochemical relapse (P = 0.015). An increase in pAkt expression was associated with reduced survival (P = 0.0098). Multivariate analysis showed that HER2 was an independent positive predictive marker of time to relapse in hormone-sensitive prostate tumors (P = 0.014). In contrast, high HER2 expression in hormone-refractory tumors was associated with decreased time to death from biochemical relapse (P = 0.039), and EGFRvIII nuclear expression was associated with decreased time to death from biochemical relapse and decreased overall survival (P = 0.02 and P = 0.005).


CONCLUSIONS
These results suggest that the HER family may have multiple roles in prostate cancer, and that expression of the proteins alone is insufficient to predict the biological response that they may elicit.
Edwards
Joanne
J
Endocrine Cancer Group, Division of Cancer Sciences and Molecular Pathology, Glasgow Royal Infirmary, Glasgow, United Kingdom. je10b@clinmed.gla.ac.uk
Traynor
Pamela
P
Munro
Alison F
AF
Pirret
Catherine F
CF
Dunne
Barbara
B
Bartlett
John M S
JM
D014408:Biomarkers, Tumor / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000096:biosynthesis*; D042341:Gonadal Hormones / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D016019:Survival Analysis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D042341:Gonadal Hormones; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D051058:Oncogene Protein v-akt