Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.
OBJECTIVE
To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients.


METHODS
We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR. The staining pattern was scored and related to clinicopathologic parameters and to outcome.


RESULTS
Low phosphorylation of EGFR in prostate epithelial cells, both in the tumor and surprisingly also in the surrounding nonmalignant tissue, was associated with significantly longer cancer-specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR immunoreactivity was significantly correlated to tumor cell proliferation, tumor vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients with metastases had significantly higher immunoreactivity for tumor and nonmalignant epithelial pEGFR compared with patients without metastases.


CONCLUSIONS
Low pEGFR immunoreactivity is associated with the favorable prognosis in prostate cancer patients and may provide information about which patients with Gleason score 6 and 7 tumors that will survive their disease even without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors give prognostic information.
Departments of Medical Biosciences, Pathology and Surgical and Perioperative Sciences, Urology and Andrology, Umea University, Umea, Sweden.
Peter
P
Hammarsten
Amar
A
Karalija
Andreas
A
Josefsson
Stina Häggström
SH
Rudolfsson
Pernilla
P
Wikström
Lars
L
Egevad
Torvald
T
Granfors
Pär
P
Stattin
Anders
A
Bergh
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020728:Transurethral Resection of Prostate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D066246:ErbB Receptors