Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer.
The epidermal growth factor receptor (EGFR) has previously been detected in the nucleus of cancer cells and primary tumors. We have reported that EGFR translocates from the plasma membrane to the nucleus. Accumulation of nuclear EGFR is linked to increased DNA synthesis and proliferation; however, the pathological significance of nuclear EGFR is not completely understood. Here, we sought to determine the predictive value of EGFR for the survival of ovarian cancer patients, through the examination of 221 cases of ovarian cancer tissues by immunohistochemical analysis to determine nuclear EGFR expression. In addition, we also examined cyclin D1 and Ki-67 through immunohistochemisty. Furthermore, we examined nuclear EGFR levels in ovarian cancer cell lines treated with EGF, and primary ovarian tumor tissue using immunofluorescence analysis. Nuclear fractions extracted from serum-starved cells treated with or without EGF were subjected to SDS-PAGE and Western blot analyses. We found that 28.3% of the cohort had high levels of nuclear EGFR, while 22.5% had low levels of nuclear EGFR, and 49.2% were negative for nuclear EGFR. Importantly, there was an inverse correlation between high nuclear EGFR, cyclin D1, and Ki-67 with overall survival (P < 0.01, P < 0.09, P < 0.041). Additionally, nuclear EGFR correlated positively with increased levels of cyclin D1 and Ki-67, both indicators for cell proliferation. Our findings indicate a pathological significance of nuclear EGFR that might be important for predicting clinical prognosis of ovarian cancer patients.
Xia
Weiya
W
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Wei
Yongkun
Y
Du
Yi
Y
Liu
Jinsong
J
Chang
Bin
B
Yu
Yung-Luen
YL
Huo
Long-Fei
LF
Miller
Stephanie
S
Hung
Mien-Chie
MC
D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
D019394:Ki-67 Antigen; D019938:Cyclin D1; D066246:ErbB Receptors